DIP Episode 138 - The Clutch Genetic Diseases Podcast (especially for Step 2CK and Step 1) + Some Thoughts on The New 2CK Exam

Okay, welcome. My name is Divine, I am a resident. This is episode 138 of the Divine Intervention Podcast. And in this podcast, I am going to be talking about genetic disorders that are commonly tested on the USMLE Step 2 CK exam. The thing is this podcast will also be extremely relevant to any person, TKIN Step 1 or any person taking Step 3. The NBME has a big focus for sure, especially on Step 2 CK and Step 1 on genetic disorders. So I decided to make a podcast that essentially catalogs all these things for you. I will essentially just talk about like the high-year presentations of these disorders. For some of them, it will be important for the pertinence to know the mechanism of inheritance and you'd also want to know like the clinical presentation and in some cases, you do actually want to know the chromosome. So those things are kind of things you want to keep down at the back of your mind. So let me just jump right into it. So what if you get a question about a newborn, right? And they tell you that this newborn has this newborn has like a flat face, has like a pecanthal folds, this kid has like, you know, like brush-filled spots. It's kind of like like little specks on the iris, right? And then they tell you that this kid has like, you know, like a single parmer crease, that's like a semi-increase. If you see that, what are you thinking about? I would really hope you're thinking about Down Syndrome. Under those circumstances, Down Syndrome, right?

Obviously you want to know that it's a trisomy, right? So it raises from a person having a trisomy 21. And the mechanism behind a Down Syndrome, right? It's like an otosomal disorder. You essentially have an extra chromosome 21. So what are some high yield things? You want to know about Down Syndrome. So for Down Syndrome, you want to know the mechanism, the thing that gives rights to Down Syndrome, right? So the most important mechanism of inheritance with Down Syndrome is that those people, they have like a maternal non-disjunction. Maternal non-disjunction is the most common cause. Again, I repeated a game. You may say, I would define this sounds loyal. I promise you it's not, okay? Maternal non-disjunction is the most common cause of Down Syndrome. But another weird one you miss your NBM exams is something relating to a Robert Sonian translocation. The thing is, if I'm not mistaken, I think in some of my self-usiology podcasts from way back when I do actually describe these mechanisms, but especially since I'm designing this with people taking the USM Ls in mind, I would just sort of keep some of that extra stuff that may not necessarily be high yield, especially for step 2 CK to a minimum. But yes, a Robert Sonian translocation is essentially another thing that causes like 1% of the cases of Down Syndrome. Basically in a Robert Sonian translocation, it's like one part of one chromosome goes to another chromosome.

So you essentially left with like a very tiny, like teeny tiny chromosome and then you left with like a big timer, like a bigger chromosome. And then the thing with Down Syndrome is you want to remember the quote screen results with Down Syndrome, right? The beta-he CG and the inhibin A will both be elevated, but those people have low levels of like AFP and astral. Okay? Those are high yield things you want to keep at the back of your mind. So again, maternal non-disjunction, most common, and then after that you have like Robert Sonian translocations, right? And again, Down Syndrome can cause multiple things, right? You can cause like, it can cause like endocardial cushion defects, right? So essentially those people essentially have like the four chambers of your heart all connected together because the endocardial cushions give rise to the septa that separate the etra and the ventricles and they also give rise to the, essentially give rise to the valves, right? That separate like the etra from the ventricles, right? So, so the two etra they won't be separated properly, the two ventricles will not be separated properly. And then you have like like an open conduit between the etra and the ventricles. That's what's known as an endocardial cushion defect. That's kind of like the battlefield phase. I mean, that's, in fact, that's the most common cardiac anomaly that's found in patients with Down Syndrome, right?

And then if you're thinking more GI, I'm determined to have like borderline atreasia, right? So, classically double bubble on an exam and, you know, obviously represent us like Bilias vomitting. I remember it's a problem with like a recanalyzation, right? For instance, gigenoatrigia, gigenoatrigia is usually not found in Downs, right? But I've just thrown it in here. Gigenoatrigia just classically arises because you have like a vascular insult in uter. Right? And then in Down Syndrome, right? Because again, if you sort of go back to step one, most of these Down Syndrome problems just arise from neuro tube issues. I mean, from a, from neurocrest issues, like the endocardial cushions that derive from neurocrest. But another thing that's derived from neurocrest that doesn't, you know, doesn't migrate properly at those like cells that constitute like your albax and myzones plexus in the distal GI tract. So, these people can have like a herch-prone disease. Essentially, they have like no cells in those ganglia, right? So, they'll have trouble pushing out up, right? So, meconium ilias can be a presentation of Down Syndrome on an endemic exam. And then remember, right, kids with Downs, right? They have like very high risk for like ALL, right? So, like acute lymphoblastic leukemia, right? And also remember that the amyloid precursor protein is found on chromosome 21. So, if you have three copies of chromosome 21, you have a very high risk of developing Alzheimer's, right?

So, in fact, it's almost uniformly, or essentially everyone, not all, but most everyone that has Down Syndrome, they will almost always get Alzheimer's by the age of 40. So, if you're seeing like an Alzheimer's style presentation in a percentage like 40 years old, you really want to think about a, you really want to think about a Down Syndrome. And what is the biggest risk factor for Down Syndrome on an endemic exam? The thing you want to think about is Advanced Maternal H, okay? The biggest risk factor for Down Syndrome on NBM is is an Advanced Maternal H. So, you may say, um, to why, why is that the case? Well, the thing is, um, in maternal bondage junction, or you may have like, you know, like a cell that has like an aberrant number of chromosome 21s, um, in the, in like the germ line. So, the problem is, remember, as, when a woman is born, she probably has like, I think maybe like 400 eggs or something like that. The thing is every month, as she goes through a menstrual cycle, she gets rid of those eggs, right? So, the thing is, when a woman is young, she had the age of 18. Let's say, um, one of those eggs, unfortunately, has like, you know, like the, like the non-disjointed chromosome that may cause a Down Syndrome. Let's say it's presenting like one egg out of the 400 she has, right? You see that there are fewer chances for the sperm to fertilize that bad egg.

But if a woman lives like 20 years, I mean, think about it if a woman has lived like 20 years, um, less issues like, you know, like 20 years past the age of 18, that's like 38. Um, that's like 240 menstrual cycles approximately. So, you're down from like having like one egg in 400 to like one egg in 160, right? So, you have a much higher risk of sending of the sperm, right? It's just like the sperm, just literally by the law of probability, the sperm just has a higher chance of getting in contact with that bad egg, um, as mom least for a longer period of time, right? So that's why increase maternal, um, each, um, is the biggest risk factor for, is the biggest risk factor for, for Down Syndrome. So again, these are high old things you want to keep at the back of your mind. Now, and I mean, obviously, right, to make the diagnosis of Downs, all you need to do is essentially, um, you essentially perform like a carotipin, right? And you'll see like, you'll look the usually like line of the chromosomes on NV Me exams, and then you look at like 21, I noticed that you have three things instead of two, right? That tells you that you're dealing with Down Syndrome. And the thing is Down Syndrome is actually the most common trisome. The second most common trisome is a Edward Syndrome, right? So that's like trisome 18. This one, I'm not really going to say much about it, but they have like three copies of chromosome 18. And again, the mechanism here is like, again, non-disjunction, okay?

And again, really the risk. Again, essentially, all these autosomal trisomes, you have an increased risk, the older mom gets, right? So like increased the maternal age, right? And the big things you want to keep at the back of your mind here is like, because many of these autosomal trisomes, they share many things and come on. So it's like, oh, like intellectual disability, you'll find it in every, essentially, every autosomal trisome. But there are some unique things you want to keep in mind with, with, with Edwards. Those people tend to have like a prominent oxypote. That's a unique feature of Edward Syndrome. Those people also tend to have like overlapping digits, right? So like their fingers cannot overlap, right? And then they tend to have rocker bottom feet. And on like, down syndrome, where these people, you know, people with downs can live to their 40s or 50s, people with Edward syndrome, they usually die like by the age of one or two, right? So it's a pretty terrible, terrible, terrible, terrible condition. So those are the high old things you want to keep at the back of your mind. So prominent oxypote, so like a big back of your head, they have like micro-nafia, so they have like a small, like a mandible, right? And then again, the overlapping digits, rocker bottom feet, kind of deal. Those are high old things you want to keep in mind with Edwards. And one way to remember that Edwards is trisome etines that remember the in Edwards and the in etine, right?

That's kind of a nice way to remember it. Remember things there. And then the least common autosomal trisomy, at least the stestidonembia mi exams. And actually by epidemiologists, it's the least common between like trisomy 21, 18 and 13 is buttole syndrome. So P-A-T-A-U, this is a trisomy 13. Again, same thing. Incrasers with increased maternal age, you have like three copies of chromosome 13. This one is terrible, terrible, terrible, terrible. And the big things you want to keep in mind here is, remember I said in trisomy 18, we have like a permanent oxypert, you don't find that here. People that have patos syndrome tend to have microcephaly, so they tend to have like small heads. And then they also tend to have like holopersencephaly. If you see holopersencephaly with any of these autosomal trisomies, the one I really want you to think about is patos syndrome. And they also tend to have like more than five fingers, right? So they have like polydactyl, these people just terrible quantum tumor formations. In fact, the prognosis in patos syndrome is a lot worse than the prognosis in edwards, which is a lot worse than the prognosis in downs. Okay? So those are the big things you want to keep at the back of your mind with these trisomies. I mean like patos syndrome, occasionally you may also see them refer to like a cleft lip and cleft palate sort of deal with these with these kids.

So they tend to have again, microcephaly, small heads, small eyes as well like micro thumb, right? And then you have like the cleft lip cleft palate, they'll have the holopersencephaly. They can also have rocker bottom feet, so rocker bottom feet is not unique to Edward syndrome. And it's also not unique to patos syndrome. Okay? But again, these are the distinguishing features to help you tell those things apart. Now, what if they give you a question about a kid that has like a cut like crying? What are you thinking about? Well, I hope you're telling me that this person you're dealing with like a, it's called like the cry of a cat syndrome is called like Redu Shah. That's a chromosome 5 defect unfortunately. That's just something you want to just come into memory. Those kids they tend to have like tiny heads, so they have like microcephaly. And then the big thing that they'll always put in an MVM question will be the high pitched cut like cry once you see that. That's Redu Shah. That's a chromosome 5 defect. Another high of chromosome 5 disorder, I guess, I'll just throw that in here is if a person has, if they give you a question about a kid like a six month old kid losing motor milestones having like fast calculations, right? That's a spinal muscular atrophy. I remember it arises. You essentially destroy the anterior horn cells, right? In the spinal cord. And it's a no-no-zoomal recessive defect actually, right?

But those kids, they have like a mutation in the SMN1 gene, right? So like the survival motor neuron 1 gene, it's primarily a low motor neuron problem, right? So again, those are high-yield things you want to keep at the back of your mind. And then if they give you a question about a kid, you know, like this kid is, you know, born with like a white reflex, right? Or they may use the boss phrase lukukuria on an MVM exam. If you see that, you want to think about retinoblastoma, right? Retinoblastoma is essentially like a gene deletion that causes the problem. And the chromosome that's involved is actually chromosome 13. That's something, again, you may say, oh, divine, this is low yield. I promise you, it's not low yield, okay? Chromosome 13, it's like you have a gene deletion on chromosome 13. So you have like a mutation in the RB tumor suppressor gene, okay? And remember that those people have a high risk of osteosarcoma in the future. And then what if they give you a question about a kid, they tell you that, oh, this kid when he was born, I mean, this kid has like, you know, like visual problems because he has no iris. And they tell you that this kid has like a flank mass. And they tell you that this kid has had like posterior rethrow valves. And this kid has like an intellectual disability. What are you thinking about here? Well, I will hope you're thinking about like a WOMS tumor. I mean, like W-A-G-R syndrome, right?

So like WOMS tumor, basically it's like wager, like W-A-G-R. I mean, there's no EI guess. So the W is WOMS tumor, right? The A is an arridia. So like a congenital absence of the iris. And then the G is like G you abnormalities, right? So these people have like G you anomalies like posterior rethrow valves, like weird insertions of the urethra and stuff like that. Horseshoe kidneys, those are things you want to keep in mind there, right? And then the R is like the intellectual disability, but prior previously, there used to call this stuff a mentorate tradition. The high you thing you want to remember about a WOMS, this W-A-G-R syndrome is that it arrises from mutations in a chromosome 11, like a deletion in chromosome 11. Again, these chromosomes I promise you, they are not low yields to commit to memory, okay? They are very important to know. Another genetic disorder that's kind of like related as well to like this WOMS tumor is like Beckwith with a men's syndrome. So Beckwith with a men's syndrome, these people are kind of like they have like this overgrowth of a lot of stuff. So they can actually get WOMS tumors as well. It's like an overgrowth disorder so they can have like macrogloseia, they can have like a big tongue, they can have like something called hemihypertrophy. So one side of their body is bigger than the other, right? And then they can have this they can describe like a redopochorjan mass in these patients, that's a hepatoblastoma, okay?

Those are all things that are related to Beckwith with a men's syndrome, okay? And those kids when they're born they can actually have like seizures from hypoglycemia because again like I said, it's an overgrowth disorder. So they have like an overgrowth of their pancreatic beta-ilett cells and then they get into trouble, right? They secret a crap tone of insulin. So they're lower their blood glucose and then they get into trouble. Now, what if you get a question about about like a 25 year old guy, you know, he got married like two years ago, he's having himself and his wife, they've tried a lot of times, they haven't like unprotected intercourse and they're not having kids. And then they tell you that this guy's like six foot one and this guy, you know, has like a lot of breast tissue, so it has like an ecomastia and it has like a micro penis, like a tiny test, like very small testicles. What are you thinking about here? I hope you're thinking about client-filter syndrome, okay? A client-filter syndrome, you want to make sure you know the chirootype and again, all these disorders, right? Like Down syndrome, Patot syndrome, Edward syndrome, client-filters, these are all things you can detect, like even toners, these are all things you can detect by essentially doing a, essentially doing a chirootype, okay? So people that have a client-filter, right? Like again, they have like 47 X XY, you want to commit that to memory and essentially the agonaz don't work, right?

And if the agonaz don't work, there's no negative feedback at the level of the anterior pituitary, right? So these people tend to have elevated levels of FSH and LH, okay? And these people are, again, they tend to have like, you know, like a micro penis, very small testicles, they don't make a lot of sperm, although some of these people have actually been successful at reproduction, but they tend to use like reproductive technologies to kind of help these guys out. But yes, they don't produce like a ton of sperm, because again, they have very low levels of testosterone, you know, they have like a female distribution of their hair, and again, basically a big thing I want to recognize, Togau is going to comastian infertility, that's the classic presentation on NBN's of client-filter syndrome. And then wouldn't be described like a girl, you know, she's like four foot, five inches tall, and they tell you that, you know, she has like toners, these one breasts, and she has like a, you know, a short posterior hairline, what are you thinking about? I hope you're thinking about a toner syndrome, right? In fact, toner syndrome, the thing you want to remember, it is like, we said that in an client-filter, it was 47 X XY, so people in client-filters have like, they do actually have a bar body. In toner syndrome, they have no bar body, because it's 45 XO, okay? So they're deficient in one of the X other excremosomes that you'd ordinary find in a normal female, right?

So the thing is that second excremosome, you kind of need it to, you know, form like over, and you also need it to form your ovaries, right? So these people, they have like, whatever already have, it's just essentially like fibro-stitial, that's why it's called like a streak ovary, right? And these people essentially, because they're not making estrogen, because their ovaries are gone, right? They won't have appropriate like secondary sexual characteristics, so they won't have like breasts, I mean, they'll have breasts, but they will not be developmentally appropriate, okay? And some other high-yield things you want to keep at the back of your mind, right? So these people they tend to have like, I think they call it like Cupid's Valkyzer, where like their elbow is sort of turned inward, right? They tend to have like the lopus tear-hair line, they tend to be like dwarfs, right? So they'll be like, fall-foot and whatever inch tall on ambient exams, and then they'll have like, they'll have a congenital lymphedema, right? So they'll have like the cystic agromas, that's why they have like the web neck, and then they will give you things like, oh like, again, like these people, very hard for them to have kids, you have like a primary menoria. In fact, if you want them to sort of group these people together with the client filters, they have something called a hyper-gonadotropic hypo-gonadisin.

The reason is called a hyper-gonadotropic hypo-gonadisin is, again, because these people essentially have like gonads that don't work, right? They don't have negative feedback, so their FSH LH, like their gonadotropins are high, right? So the people tenders, right? They'll have primary menoria, and they'll have like a hyper-gonadotropic hypo-gonadisin. Contrast this with like an athlete, you know, that works out a ton, so the whole HVG axis is shut down, those people have like more of like a hypo-gonadotropic hypo-gonadisin, right? If a person has like hyper-productinemia, or a person has like hypo-thyroidism, remember hypo-thyroidism will reach your levels of TRH, the TRH, another name for it is a product, TRH is in fact, so that can cause a hyper-productinemia and infertility. Those will also be examples of hypo-gonadotropic hypo-gonadisin, a common syndrome, right? Because you have problems with like your genareach neurons, that will also be another example of hypo-gonadotropic hypo-gonadisin. So, a toner syndrome, right? So what are the other high-youthings you want to remember about a toner syndrome? You want to make sure you remember they are cardiac abnormalities, right? So if they give you like a toner syndrome question, and the patient has like elevated blood pressures in their arms and decreased blood pressures in their legs, or they may tell you something about like a radio femoral pulse delay.

So, radio femoral pulse delay just arises because you're prior to the quotation, right? You've already given up your subclavian, right? So like you've already supplied blood to your upper extremities, but distal to the quotation, you have like a reduced blood supply, right? So those people tend to have like a delay in their femoral pulses, right? So because usually if you pull your hand on a presence, radio lottery, and you put a hand on the presence of a femoral lottery, you should feel those pulses right above the same time, right? So if you get the radio pulse first and it takes you a long time to get the femoral pulse, that's something called a radio femoral pulse delay. That's pathogen and one economy in the exams for for quotation of the other. And then the other problem that people with toner syndrome tend to have is they get like bicospediatric valves, right? And the thing you want to remember is that bicospediatric valve, right? It can cause like early onset of the etiotic stenosis, right? So like systolic ejection murmur, pulses, prophecy, tartus, or whatever, at the right of a sternal border, think about the etiotic stenosis from a bicospediatric valve. In fact, just as a sidebar, the most common cause, this is very high eutronome, for example. The most common cause of etiotic stenosis prior to the age of 70 is a bicospediatric valve. At the age of 70, it's like this whole synal calcithic stenosis, whatever that you've learned for, for example.

And then remember that these people, right, they can also get like, they can also get like horseshoe kidney, right? So they can get like recurring uti's because the inferiples of the kidney is kind of usually a stuck on the inferior mesenteric artery. So those are again, high yield things you want to keep at the back of your mind for the future. And then if they tell you that, oh, a patient like, you know, like in the 30s, they have a histro of toner syndrome, and then they tell you that the, you know, over like a six week period, they've lost weight and they have like this abdominal mass. Essentially, that's trick-over-y they have has turned into a cancer, right? Sometimes they call it like a gonadoblastoma. And that's again, one weird thing, you want to just again, fix in the back of your mind with, with, with, with, uh, toner syndrome. Okay, so I think that's all I want to say about a toner's, uh, uh, toner syndrome. And again, remember those people have, uh, they have, uh, no, they have no bar buddies because they have only one, they have only one, uh, one, uh, extremism. Now, um, let's, I guess go ahead and talk about some of these like, otozomor recessive and otozomor dominant disorders. Um, I guess maybe there are some principles I should maybe try to talk about here first. Um, one principle, I guess I'll go ahead and talk about, or you know what, just to make this podcast a little more efficient, I'll talk about the principles where, where they apply.

Um, so let's see. Okay, so what if you get a question about, uh, um, let's see, how do I start? There's so many of these disorders. Um, let me think. Um, um, um, you know what, let me actually, let me give you some quick general rules first. I think that will help you, help you with this stuff because this stuff again has a propensity to kind of get a little, get a little out of, uh, out of hand. Okay, so I guess, uh, yeah, let me talk about one principle here. So let's talk about like, uh, like some commonalities, I guess that can help you, you know, keep some of these things free because remember, which one is autosomal recessive, which one is autosomal dominant, sometimes a little hard to remember, right? So the thing is autosomal recessive disorders in general, they are enzyme defects. Okay, they usually enzyme defects. So like, g-s-expitted efficiency, for example, is in heritheta, an autosomal recessive fashion. Um, and then usually autosomal recessive disorders, right? Like those disorders tend to shrug like much earlier in life, uh, compared with autosomal dominant defects. And again, for autosomal recessive disorders, right? Obviously you need, um, to bad copies of the, of the allele, right? So that, uh, to have, uh, to have a symptoms, uh, versus autosomal dominant, where usually tends to shrug like, you know, like a little later in life, um, like haunting things, for example, doesn't shrug till, per se, like, hits their 40s, for example.

Um, and most times, um, when people have, uh, autosomal dominant disorders, it's usually like in some kind of like structural protein, excuse me, like in some kind of a structural protein, or like a receptor, right? Whenever you say like a mutation in a receptor, in a structural protein, that is almost always an autosomal dominant, uh, like, uh, the disorder in heritheta and autosomal dominant fashion. And again, you just need one allele to be bad, and then person is in trouble. Uh, usually if people have like mutations in both the leus, and it's an autosomal dominant disorder, then those kids tend to not be born, right? So like, um, a classic example of that is, um, the, I think it's like the perinital lethal form of osteogenesis imperfecta, right? Those people, um, they're, they, if you have like two bad, uh, alleles, right? Then those kids, those kids are never really, never really get born. Okay. So, um, um, so I guess let's maybe jump to the, I guess the most, almost like probably the most common on endiannes in terms of autosomal recessive disorders. Um, what if they give you a question about like a child, you know, fifth percentile for weight, uh, 10th percentile for height, recurrent respiratory infections, and what are you thinking about there? I hope you're thinking about cystic fibrosis, right? Uh, basically if a kid has like robust weights, they can have cystic fibrosis on endiannes.

You can check every endianne question you've ever seen, uh, that involves cystic fibrosis. Those kids almost uniformly have, um, have a, you know, very low, very low, uh, very low, it's even like fifth percentile or some like very low number, right? So it's a nonzomal recessive defect, it's lethal, right? In general, um, and it's a chromosome seven problem, right? Like it's in the chloride channel. Sometimes it's called like the CFTR channel, like the cystic fibrosis, a transmembrane, a conductor channel. And you may say, okay, like divine, like why do these people get all these symptoms? The reason they really get all these symptoms is that they have, um, they have, um, like very thick, like viscida secretions, right? Because the thing is, if you have a mutation in the chloride channel, chloride does not get out of the cell, so it stays on the inside. And that chloride will attract a lot of sodium from the outer. Remember, sodium is extracellular, but if there is such a high buildup of negative charge on the inside of a cell from these chlorides that never leave, right? Sodium will be attracted back into the cell. And if that sodium comes back in, water would follow. So you're essentially pulling water out of the lumina of things, right? So those people begin to have like very thick secretions, especially if like exocrine glands and like they're like a cring sweat glands, right? So those are kind of like big things to keep in mind with, with cystic fibrosis.

And there is like, it's like, like I said, it's a chromosome seven defect. There are many, many, many mutations that cause CF. But the big one you want to remember is like the Delta F508 mutation. So you essentially have like a deletion of like the phenylalanine at position 508 on chromosome seven. Okay? So again, it's defective. It's a chloride channel that's defective causes like super, super thicker secretions. And really, if you really like understand what I said about like exocrine glands and like a cring sweat glands, being like the glands that are most commonly affected, you will essentially understand the distribution of all the symptoms, right? So, so see for example, right, like in the pancreas, I mean the pancreas, many people think, oh, pancreas is just an endocrine gland, it's not the pancreas. It's only like 20% of it that's devoted to endocrine activity. About 80% of the pancreas is actually devoted, believe it or not, to exocrine activity, right? So the endocrine activity is like the insulin, glucagon, somatosdatin business, well, the endocrine activity is things more along the lines of what, I mean, exocrine activity is more along the lines of like those digestive enzymes and stuff like that. So, if those people are not releasing those digestive enzymes, you can already see that patients with cystic fibrosis, they tend to get like phatmal absorption, right?

So they will have like problems with like the phaxolubol vitamin, so they can have like my blindness from a vitamin A problem, they can have a secondary hyperprathiridesum, so like rickets, osteomalysia can a deal from a vitamin D problem. They can have like serabely taxia, right? Because vitamin E does not get any reabsorbed, they can even have like the acanthocyte osis, if you look at like red blood cells with like spiny projections, right? That usually happens when people have a vitamin E deficiency and then they can also have bleeding from the vitamin K problems they have, right? And then if you really think about it, like the submiocosa of your earways, right, contains a lot of like mucus secreting glands, right? So again, those are exocrine glands, so if those things don't work, right? Again, you have thick secretions, if you have thick secretions, you won't be able to clear the bacteria that you essentially inhale from the atmosphere. So your immune system generates like a powerful response against those bacteria, and when your immune system generates that response, release all these things like, release all these like, like you know, like very nasty chemicals that can destroy things. So you begin to destroy your earways and as your earways get destroyed, they begin to dilute, right? So you almost like have like a cystic degeneration of your earway.

That's a fully white code, cystic fibrosis, believe it or not, in the first place, because you have like your immune system become, they destroy things, you have a cystic dilation of those things, so like bronchietuses, right? In fact, CF is the most common cause of bronchietuses in the US, right? So they have like a dilation of their earways, and then your immune system recruits fibroblasts, they come and lead down like fibros tissue, fibrosis of those things, and then you have like the fibrosis part of cystic fibrosis. And then these people right, they can also have like plug-in of their, of like their, of like their semi-nifers tubules, right? So these people tend to have like infertility. In fact, the vast difference doesn't develop as well as it should, right? So many times CF is as well, like agencies of the vast difference, they can also get like meconium elias again, because they have like again very thick viscida secretions. And then remember, right, in CF patients, right? The most common, if they have pneumonia, right? Prior to the age of 21, you want to think about staff orders as the cause, but after the age of 21, you want to think more along the lines of a pseudomonas causing infections in those, in those are CFR, in those CF patients. And again, right? Again, very low birth weight and Delta F508 mutation, chromosome 7, or those are more recessive inheritance. You can treat it with a drug called Ivercaftor, if you have like a certain mutation.

So that may be something that may randomly sharpen an NV Me. So I guess you heard it here. So something you just, I guess, I keep at the back of your mind. But again, remember, it's protozoemorescesiva inheritance. And one other thing you may also keep in mind, this is something that your friends at the NV Me these days want you to know in relation to our cystic fibrosis is that kids with cystic fibrosis, I mean, people that live long enough with cystic fibrosis, they can get like a secondary primary biliary colonjitis from that. So like this is almost like it's not this one will not be associated obviously with the anti mitochondrilar antibodies. But if they have like very thick secretions from some of the like balkanliculi and whatnot, they can actually like have like, you know, like again, thick secretions there, inflammatory response fibrosis, right? So they can have like a PBC kind of picture, right? So that's again, one of these like things that may sound low, but I promise you is one of those things where most people get wrong on an exam because it's just not it's just not something they're used to seeing tested on tested on exams. And one thing I'll go ahead and say let me take a small sidebar, right? Many people have complained. I mean, I've got in lots of emails and you read it on Reddit and you read it on SDN that all the new step 2 CK exam is like really hard and all that stuff. Here's the thing you need to come to the realization of.

It's not like the mbme has invented new knowledge that they're testing. No, that's that is really not that is really not the case, right? The thing that the mbme essentially is doing these these, it seems like is that they are taking concepts that people already know and testing like on usual presentations of those things. So basically the mbme is just demanding that you have, you know, like a somewhat broader knowledge base of what you already know about. So you can not just memorize boss freezes for things and expect to like crush the exam, right? They're beginning to test like, oh, like this person knows this, right? But like this concept, but they're beginning to like find newer ways to test those same concepts. I mean, I'll give you like a classic example that I went over with my with my tutia, one of my tuties recently, right? So say for example, they give you a question about a patient with heart and up disease, right? The thing is everyone has memorized that, oh, heart and up disease, you have trouble reabsorbing like neutral amino acids. So if you have trouble reabsorbing like neutral amino acids, you will have you essentially not be able to reabsorb like triptophane, for example, and if you can already absorb triptophane, you won't be able to make a vitamin B3 or niacin. So you can have like pelagra. So you have like the four days, like the diarrhea, dermatitis, dementia and death, right? So those are things people have all memorized.

But a new style of MBME questions. So again, I'm not saying like I saw an MBME exam, but I'm just giving an example of like a phenomenon that may permit the newer MBME exams is that they can give you a question about like a patient with heart and up disease, and then they will say which of the following is an associated finding in this patient, right? A patient that has heart and up disease, they should have like low levels of five HIA in their urine, right? So you see, wait, I've heard of five HIA before, but I've never seen it tested in the context of heart and up as well. This is awake and be tested because usually when people see five HIA, they see like the high levels, uh, carstenoid syndrome, right? That's like what they've memorized, right? But obviously if a person has like heart and up disease, they're not reabsorbing triptophane. Remember, serotonin is also known as five HT, five hydroxy triptophane. So you're not uh, making enough serotonin as well, right? And five HIA is a breakdown product. So five hydroxy endolacetic acid, it's a breakdown product of a of serotonin. So people that have heart and up disease, they'll have like low levels of five HIA in their urine, right? So that will just be a unique way that your friends at the MBME can test heart and up disease, right? Just again, just essentially they're just establishing new links in material that you should already know, okay? So um, that's just something unfortunately that they're doing these days.

So just something to give at the back of your mind. So that's why the USMLA exam just seems like, oh, there's nothing I could have done to prepare for it. Just make sure that whatever you learn, learn it deeply, right? So that you can see like unique, weird, unusual associations between things if they were to test that. So I guess with that run over, let me jump back to the main topic of this podcast, right? So um, CF, right? So how can you diagnose CF, right? You can do like the sweat chloride test. Um, people see if you can even do something like there's like this conductance test, they do like between like the nasal epithelium, you may see that occasionally on exams. And then these people um, they tend to have like a low levels of like serum or tripsinogen, right? Because again, um, tripsinogen comes from your pancreas. If you have like thick secretions, you'll be hard for you to get that at tripsinogen out, uh, tripsinogen out of the pancreas. But another thing, I mean, these days, a lot of people just do like DNA testing and they make the, they make the diagnosis that way. Um, and I said that if a person with CF has pneumonia prior to the age of 20, when I think about like, staphoreus, past the age of 20, want to think about like, um, pseudomonas, one weird, unusual thing that they may throw in on an exam is, um, um, they may give you a question about a patient that has CF that has like a serious lung infection and then they die like instantly or whatever.

There's this weird bug you want to think about. It's called Bocodyrus a patient. It tends to cause very terrible, terrible, pulmonary infections in patients with, uh, with cystic fibromcy. So that is just one of those weird things you want to store at the back of your mind. So, um, um, um, the next disorder I will go to is, um, okay. Now, what if they give you a question about a child with, uh, you know, like a mousey, musty order and they tell you that this child has intellectual disability. What disorder are you thinking about? Well, I hope you're thinking about a PKU, right? A PKU phenokidonuria. Uh, don't forget that it's, uh, it's actually, um, inherited in an autosomorescesis fashion. And the thing is it arises from a mutation in this enzyme known as a phenyl-analene hydroxylis PAH, right? Um, and the thing is, um, your friends at the MBM again, they kind of know people have memorized a lot of that. So remember that fellow-alene hydroxylis uses something called tetra hydrobiobtering as a cofactor, uh, it's known as a pH 4. So there are some people that actually have, um, PKU that don't have a PAH problem. They just have a mutation in, like, the enzyme that produces pH 4. It's called like tetra hydrobiobtering reductis, okay? So if people have like a mutation in that as well, they can have a PKU. And, um, PKU again, like I said, autosomorescesis inheritance. So you have a problem with metabolizing, uh, phenyl-alene, right? So phenyl-alene will build up.

And the thing is phenyl-alene is toxic to neurons, right? So those kids tend to have, like, intellectual disability. Um, they'll have, like, a mousey-mosteodor, you may wonder, oh, divine, why do they have this mousey-mosteodor? Remember the term phenyl-alene, right? So phenyl tells you that it contains, like, a benzene ring. If you go back to, like, college organic chemistry, you remember that benzene-based compounds are referred to as aromatic compounds. So they tend to have, like, kind of like weird aromas, right? So that's why if phenyl-alene and, like, derivatives of phenyl-alene build up because a person has PKU, they tend to have, like, unique orders. Um, in fact, you notice that many of these amino acid disorders those, because many amino acids contain benzene rings, those people tend to have, like, uh, kind of like weird, uh, body, um, orders. And then, uh, the thing is, in general, if you, if you fix PKU by essentially cutting out phenyl-alene from the diet, like, pretty early, um, those kids can actually have mammal intelligence, mammal life. You just need to do it, like, within the first couple of days of life. And, um, what are some other things you may find in a person with a PKU on an NBM unit? So they may be, uh, our binosaur, right? So they may have, like, arbonism. So what's the mechanism behind that, right? The thing is, phenyl-alene hydroxyl is ultimately converts phenyl-alene into tyrosine.

Tyrosine, uh, through a series of pathways, uh, ultimately with, like, tyrosine is made into melanin. So if people have PKU, they are not making tyrosine, if you don't make tyrosine, then they would not have any feedstock for the production of melanin. And that can cause, uh, a skin hypopigmentation because they're essentially, uh, albinos. So that's a high-yoda thing. You also want to keep at the back of your mind with, uh, with a PKU. And, um, again, PKU, it's part of the newborn screen. And again, you restrict phenyl-alene in the diet. Um, another classic NBM question is, is that these people should avoid that, like, uh, artificial, like, sweat nurse, right? Things that contain an asparting. Um, that's, again, something you want to keep, keep at the back of your mind on exams. And then, um, uh, if mom actually has PKU, um, you, they can give you, like, a very super unusual NBM, like, OB-GYN question about, like, precautions that have to be taken by mom that has like a history of PKU. The thing is, if mom has a history of PKU, she actually has to be put, like, on a very good diet, uh, during pregnancy, because if phenyl-alene in a cumuletin mom, it can actually cross the placenta and cause a lot of issues for the, for the baby. So that's all I think I'm going to say about a PKU. Now, when they give you a question about a patient and they tell you that this patient, you know, he's like 25 years old and this patient already has like, osteoarthritis.

And then they tell you that, uh, they did like some imaging or got like some synovial fluid or whatever. And they notice that this person's joints looked black, right? Or they tell you that this patient has like, this coloration of their ears and their nose. If you see that, what are you thinking about? I would hope you're thinking about, uh, alcaptoneuria, right? Occasionally, on NBM, instead of calling it alcaptoneuria, the mecholita ocronosis. Basically, these people have, uh, it's again, a resume recessive problem. Uh, they have a, uh, deficiency of the enzyme known as a homogen tizika acid oxidize. So the unfortunate thing that happens is that homogen tizika acid will build up. And homogen tizika acid, it loves to bind to connective tissue. It loves loves, loves connective tissue. In fact, uh, homogen tizika acid has like, uh, like a cartilage fetish. So it binds to cartilage very avidly. And wait, you find cartilage. You find cartilage on your ear, right? So, um, that's why those people tend to have like, disclosure of their ears. You find cartilage in your nose. That's why they tend to have like, disclosure of your nose. I remember you have like, a tickler cartilage, right, in your, at your joints, right? So those people can have like, uh, like a very dark, uh, discoloration of their joints. And the thing is, when the homogen tizika acid deposits in their joints, they can get like very early, like, osteoarthritis, right?

So if you see like, osteoarthritis, young person that has like a discolored nose and a discolored ear, um, I really want you to think about, uh, outcap to, outcap to Nuri, okay? Um, and again, it's like I said, it's an orozomal recessive disorder. That's kind of like the big thing you want to remember. You want to remember with the disease. And then another like key high orozomal recessive disorder is like, albinism, right? So again, I cannot alluded to this already. That tyrosine is converted to melanin by an enzyme known as tyrosinis. So the thing is, if a person has a mutation in tyrosinis or deficiency of tyrosinis, um, they will not be able to make melanin, right? So that can cause an albinism, especially like the ocular cutaneous albinism, right? And remember, melanin kind of helps you reabsorb some of those like, you know, like bad uv, like the bad uv radiation that comes from the atmosphere. So people that actually have albinism, they actually had increased risk for like skin cancers or like bizocel, schlumosel, question numbers of the skin. So they can say, they can give you like a question about a patient that has a history of albinism and this, say, this person is at increased risk for which of the fully malignancies in the future. You want to think about a skin malignancy, right? Like, again, like bizocel or like schlumosel, question number. And then what if they give you a question about a kit that has like a chair-writ spot on the macula?

And this kit, you know, is kind of like losing motor milestones and they tell you that this kit has no hepatosplimomycheli. What are you thinking about? I would hope you're thinking about like T-Sax disease, right? So the thing with T-Sax disease, again, I have like a formal podcast on the Lyosomal Surgery diseases. But again, in this podcast, I just want to talk about the ones that are super, super, super high-yout, right? So the thing is, the Lyosomal Surgery diseases, they're kind of like nebulus for a lot of people. But to be honest with you, if you like really like sit down and understand them, they actually make kind of like perfect sense. At least the major ones that are tested on the USMD exams, right? So for example, the, I guess general concept behind many of these diseases is you essentially have like remember your Lyosom is like the waste basket of a cell, right? It breaks down stuff. The thing is if Lyosomal Surgery disease means that you have trouble breaking down certain things in the Lyosom because you have a deficiency of like a certain enzyme, right? And if you have a deficiency of that enzyme, those things build up within the Lyosom. And then those cells that contain those Lyosom that are storing all those bad things that they cannot break down, those cells become big. And as those cells become big, you begin to have this function of those organs. That's kind of like the big picture behind the most Lyosomal storage diseases.

So take for example like Tessac's disease, right? Tessac's disease it arises from a person having like a mutation in a in a Hexosaminidase A, right? So the mutation in Hexosaminidase, so the thing that happens is they have a buildup of something called a GM2 ganglocyte. Now the name GM2 ganglocyte should already tell you something ganglial, so that means you should find it in neurons, right? So the thing is this Hexosaminidase enzyme is expressed very heavily in like neurons. So these people tend to have mostly neuro-based problems, right? So they tend to have problems like at the level of the CNS, right? So like as these cells, as these neurons get bigger and bigger and bigger and bigger and bigger because the GM2 ganglocyte is accumulating, right? They tend to have like neurons that kind of like dilated and just huge, huge, huge neurons. So they tend to have like, you know, like intellectual disability, they'll have like problems with like the amurumal stones, right? And most times this kid on these kids unfortunately dead at the age of like two, two or three. And again, because it's an enzyme defect, that should remind you that it's inherited in an orosomal recessive fashion. And you may say, okay, why do they have like the chair, it's put on the macular, right? Again, remember they're ganglion cells in your retina, if you sort of go back to like studying for like whatever neuroblock you had in in med school, they're ganglion cells in the retina.

As those ganglion cells get bigger and bigger and bigger and bigger and bigger and bigger, right? Because again, those include the GM2 ganglion cells that is building up in those. They begin to compress on the blood vessels that run through the retina. So those blood vessels, they are like chronically engorged with blood, right? And because you have like, like, you know, like high density of like retinal neurons around like the central part of your eye, right? Especially like the macula. Those blood vessels that are becoming more prominent is what essentially gives you the chair red spot in the macula. So that's why people with T-Sax disease, they tend to have mostly neurologic problems and retinal problems, okay? So chair red spot on the macula, but in general, they have no hepato splenomegaly. That's a high oath thing to know. And remember that T-Sax is pretty common in kids that have like, you know, that are, you know, like people that are of like Ashkenazia, Jewish heritage. So that's something you want to keep at the back of your mind. Another high your disease to keep in mind is like an even pick disease, right? So this one, they have a deficiency of like a Sphingo Mylinis, right? Remember Sphingo Mylinis, just as the name says, it helps you break down Sphingo Mylin. So the thing that builds up is a Sphingo Mylin, right? And the thing is Sphingo Mylin, like this Sphingo Mylinis, again, it's expressed very commonly in the central nervous system, right?

It is very, very commonly like in the retina. And unfortunately, it's also expressed pretty heavily by macrophages, right? Like macrophages that you find in the reticulo and the thelial system. So if you're following along with my explanation so far, you can already begin to understand that, again, you have like the big neurons, right? So they'll have like, diluted neurons. So they'll have like, again, like, intellectual disability. They would have, they would have like, Mudo, like they'll lose their Mudo milestones. They will lose, they'll have like the chairwrestle and the macula as well, again, because those diluted, like retinal ganglion cells are compressing those blood vessels that run through the retina. So they'll have like the chairwrestle and the macula. Another weird thing you will also see is, because you may see like divine, why does TASAC's disease involve, not involve the liver and nimenpic involve the liver, right? Like you remember, I just said that the macrophages that you find in the reticulo and thelial system, right? So like, remember your reticulo and thelial system is essentially your liver and your spleen and your bone marrow, right? There are those macrophages, right? They begin to, because they have like the mutation in the sphingo-mylinis, right? They begin to expand and like they begin to accumulate the sphingo-mylin. So those macrophages expand, right?

So any organ essentially that constitutes your reticulo and thelial system is also going to expand and also begin to have dysfunction, right? So for example, those people have like a padomegaly, they will have spleenomegaly. I mean, if you have spleenomegaly, remember a bigger spleen can sequestromo pleaklets. So these people tend to have like thrombocytopenia, right? So those people have like a padomegaly. So you also see again, all those are kind of like similar symptoms to TASAC's disease, but again, this hepatic and spleenic involvement, just because these people, the macrophages of the reticulo and thelial system kind of express that as sphingo-mylinis enzyme in like very high quantity. So if they have a mutation in that enzyme, again, autosomal recessive inheritance, they don't break that sphingo-mylin. Those things build up when you begin to have dysfunction of those different of those are different organs. And again, the main big disease is very common in a in a people of Ashkenazi, a Jewish heritage. Now, the thing is what if you get a question about a patient that they give you a question about, you know, like a patient that has like pancytopenia. And so like their pleaklet count is low, their white blood cell count is low, their hemoglobin is low. And then they tell you that they do like a bone marrow biopsy and they find like they find like macrophages with like a tissue paper like cytoplasm, right? Like crumpled paper like cytoplasm.

If you see that, I will really hope you're thinking about a Goshis disease. A Goshis disease, I mean, arises from a deficiency in an enzyme called a glucose cerebracides. So glucose cerebracides, the thing is again, knowing the distribution of glucose cerebracides kind of helps you predict a lot of what's going on with these with these patients, right? So glucose cerebracides again, it accumulates for the more, in fact, glucose cerebracides has very low accumulation, like it's very likely expressed in the central nervous system. So patients with Goshis disease, they tend to not have much in the way of neurological issues. But glucose cerebracides expressed in very, very, very high levels in those macrophages that again constitute the reticulo endothelial system. And again, I said your RIS system involves liver, spleen and bone marrow. So again, if you have like those macrophages, they accumulate the glucose cerebracide because you have a glucose cerebracide is a deficiency. Those are like the presence liver or get back. So they'll have and liver and spleen with both get back. So they'll have a plateau spleen omega-le because the spleen is getting this equestria, pleatlet, so they get a thrombocytopenia. And again, because the bone marrow is overtaken by these these macrophages that are filled with glucose cerebracide, you have like ineffective erythropoesis, right?

So those people have like an anemia, they only quite blood cells, so they'll have like a leukopenia, they only make enough pleatlet, so they'll have like a thrombocytopenia. So and these people tend to have like a lot of like joint problems because again, remember your bones, right? Contain bone marrow, right? That's kind of obvious, right? So those are again all things you want to keep at the back of your mind with with these disorders. And then if they give you a question about a kid, you know, that has like like corneal cloud in and has like a coarse facial features. I would really hope you're thinking about like a like a holler syndrome, right? Remember holler syndrome? It arises when a person has a mutation in alpha L-iduroneides, right? So you see like corneal cloud in, coarse facial features, think about holler syndrome. The way I remember that it's a mutation in alpha L-iduroneides is that there is an L in holler and there is an L in alpha L-iduroneides. Contrast this with hunter syndrome. And actually, let me see one less than about holler. So holler syndrome has is inherited in an autosomal recessive fashion. Hunter syndrome is kind of like weird in that it's actually inherited in an ex-linked recessive fashion. Just remember that the hunter like max and x-pawn or whatever, that's like this numonic that has passed down from our generation to generation. So hunter syndrome, it's ex-linked recessive inheritance.

And the mutation is in an enzyme called like alpha L-iduroneides, sulfaties, so like iduroneides, sulfaties, if you may. And where I remember again is hunter has a T in it, iduroneides, sulfaties, there are many T's in that in those enzymes names, right? So those are, and usually people with hunter syndrome, they do not have corneal cloud in and they do not have coarse facial features. That's the way you can tell hunter apart from holler syndrome. And one of the last thing you want to remember kind of like a commonality between both disorders is that they have a build up of a heparin and a dermatan sulfate. So again, those are high yield things you want to keep at the back of your mind for for for NBM exams. And then I will just again like spend again because I want to make this podcast all in compassion. So I'm just going to spend some I guess short time talking about some of the high yield things you want to keep in mind with with glycogen storage diseases, right? So like the first one is like one year's disease, right? That's like the type one GSD. You essentially have like a mutation in a glucose six phosphaties, like a deficiency of glucose six phosphaties. And again, it's all autozomeric, excessive inheritance because again, it's an enzyme defect. So these people have like a deficiency in a glucose six phosphaties.

And the thing is again, if you think really the key to remembering what happens in this like sozoma storage diseases and in these glycogen storage diseases is essentially just remembering where these enzymes are located. If you remember them, most of the findings make absolute perfect sense, right? So like in one gig disease, that's like a glucose six phosphaties deficiency. Remember glucose six phosphaties is necessary for you to convert glucose six phosphaties to glucose, right? So essentially if you're an organ that participates in glucose neogenesis, you'll have issues if you have one gig disease, right? So remember the liver, the liver is like the big, big, big, big, big, big operator for glucose neogenesis, right? So these people tend to have, these people tend to have like a patoz planumegaly, right? Because again, the liver is dysfunctional because you may think about it like, oh, why does the liver get dysfunctional? Well, if you don't have activity of glucose six phosphaties, you have an accumulation of glucose six phosphates in the liver. And if you have an accumulation of glucose six phosphaties in the liver, glucose six phosphates is various, motically active, right? So the attract water to the liver. So those hepatic cells will expand so you have a patoz planumegaly and then over time they can explode, right? And then those people ultimately get like, you know, like really bad liver failure.

And the classic presentation here is that these people get like hypoglycemic between males, right? Because again, glucose neogenesis doesn't work because remember the thing that keeps you going between males when you're not eating is glucose neogenesis, right? So these people, if they have, if they're not eating, right? That's why they always say, give these people corn starch. I mean, they are not eating their symptoms become as saturated if you may. And again, remember, Von Gerk's disease, it's a type one GSD, or a sum of recessive inheritance deficiency in glucose are six of phosphaties. These people do not have muscle symptoms, okay? Because the muscles ordinarily do not express glucose six phosphaties. Now the second one is usually easy for a lot of people to remember like GSD type two, that's a pump-based disease. The enzyme that is mutated, right? Sometimes on NBM Es you may see one of two names. So unfortunately you need to memorize both. One NBM Es see on NBM Es is like alpha-1-4 glucose sideys, right? Alpha-1-4 glucose sideys, that's the enzyme that's a mutated in a type two GSD, so like pump-based disease. But I'm not even for alpha-1-4 glucose sideys, it's actually something called acid moties, right? And the thing is these people, these people tend to, again, the big thing I want to remember here is that they have heart failure, right?

They have like big-time heart failure because again, muscles that have organs that have a lot of glycogen, so cardiac muscle for example, they have like big cardiomegaly, they get like a diluted, a stylocardiomyopathy, and most times they are dead by the age of two. And the most common cause of death in kids with pump-based disease like type two glycogen story disease is a heart failure, okay? So if you see heart failure in the setting of glycogen story disease, think about pump-based disease. What type three GSD? That's the one that's known as a chorus disease. Chorus disease arises because people have a mutation in an enzyme called the debranchine enzyme, and this is where again unfortunately there are two names you need to remember. One name is debranchine enzyme, the other name is alpha-16 glucosides, so please do not mix this up. In pump-based disease, the mutation is an acid mortise, also known as alpha-14 glucosides. And chorus disease, which is the type three GSD, they have a mutation in alpha-16 glucosides, which is also known as debranchine enzyme. And really the way to keep those treaties remember that type two comes before type three, and acid mortise contains an A, A comes before D, right? Acid mortise, debranchine enzyme. And then if you look at the numbers alpha-14, four is an earlier number than six, so again that's a way to sort of keep those things, keep those things straight on the exams.

And the thing is people that have chorus disease, the thing is the debranchine enzyme is expressable in liver and in muscle. So on NBM exams, people that have chorus disease, they'll have muscle problems and they'll have liver problems, so they'll have a pyrospinal megalith. And then the last glycogen story disease I'll talk about is macarose disease. Macarose disease, it's a problem with like glycogen phosphorelease. Occasionally on NBM, you may see them in the factory as a myophosphorelease. Essentially these people, these people, they have like a lot of like muscle cramping with like exercise or like playing games, little competitive sports or whatever. So that's kind of like the big presentation. You may see, different, do they have liver symptoms? They really do not have liver symptoms. Because yes, glycogen phosphorelease is expressed in the liver, but it's the muscle iso-form of glycogen phosphorelease. That's why it's called myophosphorelease that is affected in macarose disease, which is a type 5 GSD. So again to summarize, the glycogen story disease is like high level review. There's four of them you need to, there's actually like 14 of them, but there's only four, you need to know for your exams. There's type one, type two, type three, and type five. Okay, remember there's a type one, and then if you add the numbers two and three, you get five. That's what we remember that all you have type one, type two, type three, and type five.

And the thing is, easy way to remember this like again high level review, there's one that affects only muscle, that's type five GSD, that's macarose disease, there's one that affects only liver, that's type one GSD, that's one GERG's disease, there's one that affects liver and muscle, that's type three GSD, chorus disease, and then there's one that causes heart failure that affects the heart, that's type two GSD, that's pumpase disease. So one affects just liver, one affects just muscle, one affects both, one affects the heart. That's the way to keep those things straight on on NBM exams. And then one last I guess like sozoma like storage disease I'll talk about is actually true, I'll talk about real quick. Remember that if a person has, what is this thing called? I sell disease, I'll just say like one or two words about some of these diseases, like I sell disease, remember it's those people like have problems like putting like monosix phosphate residues on stuff, right? They have like a like a mutation in like a forceful transferase. So they cannot put like a monosix phosphate residues on things, so those things are not targeted to the lysosome, they are targeted to outside the cell, so that causes a lot of problems.

And then another disease you may think about, these are like more like fatty acid or oxidation disorders, there's one called like MCAT deficiency, like so like a medium-chail, medium-chain isoqueed, hydrogen is a deficiency, those people have like problems with like beta oxidation, right? So they ultimately have issues, you know oxidizing fatty acids. And this is actually, it's like a fatty acid again, breakdown or defect. And those people they tend to have like elevated levels of like isocarnitins. So people that have the MCAT deficiency, they have like high levels of isocarnitins, contrast that people that have like a carnitine deficiency, so like a cat one or a cat two mutation, they tend to have like low levels of isocarnitins. So those things are both fatty acid oxidation disorders, but one has high levels of isocarnitins, that's like the MCAT or the L-CAT. So like medium-chain isoqueed, hydrogen is or like long-chain isoqueed, hydrogen is the disorders, they tend to have like elevated levels of isocarnitins because those steps come to the isocqueed, hydrogen is step. And then people that have carnitine deficiency, they have low levels of isocarnitins. And then if you notice I said medium-chain and then I talked about long-chain and then I talked about one thing I guess I've neglected to talk about. And again, I'm just, this is again, I'm just sort of talking through these things as they come to my mind. I'm very long-chains.

Remember very long-chains, like very long-chain fatty acids are not metabolizing the mitochondria, they're actually metabolizing the peroxysome. So if you have a problem with like some peroxysomal enzyme, you can have trouble metabolizing like very long-chain fatty acids. The post-achal disorder you probably want to remember for exams is something called like adrenal lucodistrophy, right? Adrenal lucodistrophy, right? So luco means white, right? So these people have like a lot of like demyelination, like in the white matter, right? And they'll have like problems with their cerebellum, so they'll have like a taxiia. And usually these kids are dead by the age of two. Basically if you see a kid that has like very bad demyelination of like white matter, like that's the class, like they'll usually throw in that sentence on an ambient exam. Think about that adrenal lucodistrophy. Remember it's a peroxysomal disorder. So they have problems with beta oxidizing, very long-chain fatty acids. Those are things again, unfortunately your friends on the ambient exam love to love to test. And again, I know like this, you may say the vine, you're being a little too much in this in this podcast, but again, I promise you, I promise you these genetic disorders, they're very, very, very, very high yield to know for exams.

You won't believe me, but again, I promise you as a person that has stood up for a long time, these things are very high yields to keep in mind for ambient exams, like step one, but especially like step two CK, step two CK is showing a lot of love for genetic disorders, so I would definitely know these things if I were you. And then, I mean if you read like the step two CK like content guideline, the list like a decent number of genetic disorders, they kind of expect you, they kind of expect you to know. Now, what if they give you a question about a person that has a, that has, like they tell you that this person, like they're that type of an MID, of like 30, and then this person has like the coming to the ED severe chest pain, you see STL evations, and this is like a 19 year old, and they tell you that on physical exam, you notice that this person has like Zantelasmas, and they have like Zanthomas, on like the Achilles and all that stuff. I really hope you're thinking about a familial hypercholesterolemia, and the thing is familial hypercholesterolemia is actually inherited in an OZOMO dominant fashion. In fact, I'll put it this way. I'm going to try to like, if you notice, I spent a lot of time on OZOMO recessives, I'm sort of beginning to deep my two in two OZOMO dominant disorders with this part of the podcast.

So, remember I said that, remember I told you like this trick, that OZOMO dominant disorders tend to be like structural defects, and also tend to be like receptor defects. So, the thing is, the disorder I'm referring to with this first case I just presented is a familial hypercholesterolemia. Basically, the problem arises from a mutation in the LDR receptor. So, if you have no LDR receptor, you have a lot of problems. These people, they tend to have like very accelerated, arthrochlorotic disease. So, they can get like M Is, like in their teens, in their 20s. Usually, they will give you some history that that died at like 35 from an M Is or something. And then on physical exam, because again, if you have no LDR receptor, you're not going to clear LDL cholesterol. So, it begins to accumulate in like thin parts of your body. Your eyelids are very thin. So, you see like X-anthin lasmus. Again, they can have like this anthomas, and like the akibis and all that stuff. So, it's again a lot of dominant inheritance. The primary problem is like with LDR receptors. And again, they have like super high levels of cholesterol. Obviously, if you want to treat these people in general, on MBM is you want to treat them as statin, right? So, like atover statin or starting like your HNG query, doctors inhibitors. Occasionally on the exam, especially these like new PCSK9 inhibitors that all end in QMAP. So, like alero QMAP, evolved QMAP.

They have actually very good for treating these familial hypercholestrolemias. And if you're taking in step 2, CK, you can sort of like turn out your ear for the next like one minute. But for purposes of people taking step 1, these are familial hypercholestrolemias. There's like five defects that cause these problems. So, like there's like the type 1 way. You essentially have like no LDR receptor. This one is terrible, right? There's the type 2 way. You make LDR receptors, but you don't get them to the surface of the cell, right? So, because if you actually sort of go back again, like deep into your pre-technical sciences, remember this like exosytosis pathway where you start to sort of start like the rough endoplastic reticulum and then you go to the goji and all that crap. The thing is the goji is where you make these LDR receptors. But if you have trouble in that like cascade that ultimately gets it exosytosis, like targeted to the surface of a cell, that's actually a class 2, like a type 2 familial hypercholestrolemia. And then the type 3 is where LDL just has trouble binding to the LDR receptor. This if I'm not mistaken is actually the most common kind of familial hypercholestrolemia. And then there's the type 4 where the LDL kind of like binds to the LDR receptor. But remember that LDL receptor with its bound LDL ultimately is endosytosting to the hepatocytes. If you have defects in that like endosytosis process, that's like a type 4 familial hypercholestrolemia.

And then if you have trouble like recycling the LDL receptor, then that's like a type 5 defect. So those LDL receptors, your body essentially like you know through like a complicated process tries to reuse them. But if you have like problems with that like recycling process, then you obviously put less LDL receptors on the surfaces of your hepatocytes. So you have a lot of trouble like clearing LDL. So those people have hypercholestrolemia. So again those are big time things you want to keep at the back of your mind with these exams. And then wouldn't be give you a question about a kid, you know there's like six foot five inches tall bloody bloody bluff. And then this kid has like hyper-extensible joints and has like weird displacement of the lens and comes the only tiering chest being, radiating to the back. I really hope on that those circumstances you're thinking about like Marfan syndrome, right? So Marfan syndrome again, or the Zomo dominant inheritance. Remember it's a, it arises from a mutation like on chromosome 15, right? That's the other chromosome 15 pathology you probably want to like screw into your mind somewhere like those predar Willian, predar Willian, injouments, in terms of talk about those a little bit down the line probably like in the next couple of minutes. But Marfan syndrome, right? Again, it's a chromosome 15 defect. You have like a mutation in like the Fibreling gene, like the FBN1 gene, right?

The thing is FBN1 is kind of important for a little thing, right? But for the most part, it really helps you maintain like the integrity of like elastic fibers, right? Elastic fibers. So if you have like problems with like maintaining the integrity of elastic fibers, things that kind of like need those elastic fibers begin to get into a lot of trouble, right? So for example, like the valves, like especially like the mitral valves, right? Those people tend to have like accelerated like mix some of those degeneration of their mitral valves, right? So they can get like mitral valves prolapse. Again, if you have problems with the scaffolding for like elastic fibers, remember you find a lot of elastic fibers in the media of your blood vessels. And those elastic fibers obviously like because remember arteries, right? They sort of like pulsate, right? So the dilute and then the relax back, the dilute and then the relax back, the dilute, the relax back. If you have problems with those elastic fibers because their scaffolding is not right, because you have like a Fibreling defect. Those people when their other, when their other is dilute, there's not enough to let them, there's not enough to let them like snap back. So if they don't snap back, they just keep diluting, diluting, dilating, diluting. And those people can ultimately get aneurysms, right?

In fact, one of the most common causes is not the most common, but one of the most common causes of death in patients with morphines is like aortic dissection, right? And they also tend to have like these ascending aortic aneurysms. So you may see divine weight. Why do they tend to have problems at the level of the ascending aorta and fewer problems at the level of like the abdominal aorta? Well, here's the thing. The reason they tend to have those, like a predilection of their problems for the ascending thoracic aorta is that think about it. What part of the aorta has the highest pressure of blood? It's obviously the part that's like right after the left ventricle, right? Like the ascending thoracic aorta, right? So that's why they tend to have more dilution of their ascending thoracic aorta. So again, they get into trouble. Those people tend to get into trouble pretty pretty quickly with that, right? And if you kind of think about it, right? If those people's ascending a thoracic aorta's dilute, that would pull the aortic valve leaflets apart, right? So pieces with morphines they also tend to get like a lot of like aortic regurgitation. And if you sort of think about it like again because they have these fibrillin defects, they can have like problems in the circle of willis. So like an anterior communicative aneurysm or so they can rupture those things and then they can get like a sub-racnoid hemorrhage kind of deal.

So again, those are high yield things you want to keep at the back of your mind. They can even give you things relating to like the lens of their of lenses of their eyes, right? So like because the lens, right? The silery, a part that connects to the lens, so they're uses like those elastic fibers. So if you have problems with that, again, you have like a lens of longsition. Their lenses are sub-located like I think like up and out, right? So like a topia lens versus I guess or homocystinuria. Those people tend to have that one is more like an orozumul. I really can remember so let you look that up on your own. But those people tend to have their lenses are dislocated like down and in, right? And I guess let me take a small sidebar. To be honest, I really did not mentally like homocystinuria is very loyal for the USML Es. But for people taking step one, I guess let me go ahead and just throw in some key things here. Because many times your friends at the NBM will write the questions closely enough to where they can make you make mistakes on your exam. So here is something you want to keep at the back of your mind. People that have morphine syndrome, they tend to have their lenses dislocated up and out. People that have homocystinuria, they tend to have their lenses dislocated down and in, right? But both of those people are told they have like a morphineoid habitus.

But people that have morphines, they tend to have normal intelligence, people that have homocystinuria, they tend to have intellectual disability. And then another thing that may also help you differentiate those things is people with morphines, right? They tend to have again more like the the mutation in like fibrillin, like the fibrillin mutation. People that have homocystinuria, they tend to have problems with like a sister thionine, a bit of synthase, right? So like they have like CBS deficiencies. And one thing you want to remember is three things that it will have at the levels of homocystine. Again, this is just a sidebar talk is problems with vitamin B6, B9, and B12. Okay? So I'm going to leave it at that and I think I'm going to go ahead and go ahead and move on. Now, what do they give you a question about a patient? And this patient, you know, they tell you that this patient has like problems with like wound healing and they have like hyper extensible skin and hyper extensible like joints. I would hope you're thinking about I would hope you're thinking about like, let's download some syndrome. Let's download syndrome, again, it's a structural problem. So that tells you out of the bad that it's a orosomo dominant inheritance. And again, these people, they there are many kinds of, there are many kinds of mutations that can cause a LSDANLOS syndrome.

The big one I want you to remember is like a mutation in like type three collagen does that one that causes like the vascular LSDANLOS? I mean, there again, there's many, there's like the one there's like LSDANLOS type five and all that crap. But again, the one I want you to remember is like type three collagen defect LSDANLOS syndrome. And the people who are LSDANLOS right again, because they have these defects, they tend to have they tend to have, they tend to have like again, the hyper extensible skin, the hyper extensible joints, they tend to have like aortic dissection, they can have like a thoracic eortic aneurysm, can be like for similar reasons as we have as I explained for my friends. But some other weird things you want to keep at the back of your mind with these people is they tend to have like wound, the he's since right. So they have like a lot of like troubled like wound healing. And they may give you a question about a patient that has like a ruptured of the colon that has LSDANLOS. The reasoning behind that if you kind of think about it, right? As your thick old material is approaching the colon, a lot of that, a lot of the, come on, I think a lot of the water has been reabsorbed. So because a lot of that water has been reabsorbed, you have like thicker material. So to sort of push that material out, it needs to generate more pressure. Well, the thing is the wall of your colon.

And again, the wall of your GI tract just in general also has a lot of like type 3 collagen in it. So if you have like those problems, you can as you're trying to like poop, poop, poop, poop, especially if they have like bad constipation, they can explode and rupture their rupture their colons, right? So those are again, how you things you want to keep in mind, that's unusual, but a very common NV Me presentation of LSDANLOS syndrome. And then, wouldn't they give you a question about a patient that you know has like a, like a blue scleror? And then they tell you that they have like a lot of like problems like like a lot of fractures and all that crap. What are you thinking about? And it's like a short kid. I hope you're thinking about osteogenesis, osteogenesis imperfecta. I remember it arises from like a type 1 collagen defect. So you have your friends at the NV Me, they put like COL1 something, something, something, as the gene defect. And again, it's also a rosomal or a rosomal dominant inheritance. Now, what do you think of your question about a kid that has been having like episodes of like hematuria? And they tell you that this kid also has like hearing problems and has like a cataract. I hope with that you're thinking about like how ports syndrome. I remember outboard syndrome. It arises from like a type 4 collagen defect. It's actually like ex linked dominant inheritance. So it's a type 4 collagen defect.

Well, the thing is type 4 collagen, you'll find it on in the, like the lens of the eye. So those people can have like cataracts. You actually find it in the ear. So those people have like hearing problems and you find that the glomerular bismine membrane. So these people tend to have like a kind of a nephritic syndrome. One type 4 collagen related thing that I wouldn't want you to mess up on your exam is Oh, come on, divine thing. There's this type 4 collagen problem. It's not a genetic problem, but it's more like you make, yes, yes, yes, I remember. So yeah, so it's when you make auto antibodies against like one of the subunits of type 4 collagen, that'll cause good posture syndrome. So remember in good pastures, those people have like kidney problems, right? They'll have like a rapidly progressive glomerular and fritis. And then they'll also have like hemoptysis because type 4 collagen is also found at the, like the basement membrane, like you find type 4 collagen in the lungs. Remember, those people will not have a sinusitis. Yeah, that's your other type 4 collagen, a problem you want to keep at the back of your mind. And then they can also describe a kid, you know, that has like short stature and the, at the ask you questions about like problems with like the longboard growth and this kid is like a dwarf or whatever. Maybe you want to think about a congeural pleasio with that. It's a mutation in like an endocondral or bone formation, right?

So the mutation is like in the fibroblast growth factor receptor 3. So that's actually something you want to gain. Just start the back of your mind for exams. And then if they give you a question about a patient that has, you know, like coffee or late spots and they have like multiple grotesque on their body. So like essentially, right, I hope you're thinking about like NF1. I remember NF1, it's a narosomo dominant disorder. In wolf chromosomes, chromosome 17, and you would want to remember like some classic findings, right? In, in, in, in a NF1, right? So in NF1, you tend to have like the coffee or late spots, they tend to have like the, although remember, coffee or late spots does not just mean NF1 on MD and E3. You need to, they will give you more stuff, right? So read the context of the question because like one of the Fankuni prob syndrome can also cause a coffee or late spots, although those people tend to have like problems with like they are like they have like absent digits or like problems with their radios or whatever. But that's a different discussion for another day. But in, in, NF1, they tend to have like the coffee or late spots, they have like the neurofibromas. I remember, they can get like many engeomas, they can get like few chromosomes atomas, right? So they can have a lichinogen, right? Those are like hematomas in the iris. And you may see the why, why do these people tend to have all these problems?

The theme is, unfortunately, the gene product of chromosome 17 that's mutated in NF1, it's called like neurofibromine. The theme is neurofibromine is tumor suppressor gene. The theme it does is it actually suppresses for those that again, studying for step one, it suppresses like something this protein called like P21, that's kind of like involving like that ras cascade. So if you have a mutation in the suppressor of P21, then things begin to grow like aberrantly, right? You have like grotesque of all these like fibroblastic tumors and all that stuff. And they get all these, they end up getting all these all these problems. And so those are again like big things you want to keep at the back of your mind with with NF type one. NF type two, right? It's also again a resumodominant inheritance but the mutation is in chromosome 22. The big thing you want to remember here is those people tend to have like the bilateral acoustic neuromas, okay? And again, you may say, okay, define why do these people get all these tumors? The thing is the gene product here is something called like Merlin. Merlin essentially, it's a tumor suppressor gene. What it does is it tells cells when they've grown too much. When they begin to like, you know, like close the apples to each other, it tells those cells to stop growing. But if you have a mutation in those in the Merlin protein, right? Then you lose that ability. So cells, they don't respect their bounces anymore.

They keep growing, growing, growing, growing, growing. And then you can even have like cancers. Although most of these things tend to be like benign malignancies. Because if you if you again dig deep to your preclinical sciences, you're probably lent about this thing with like a cancer cells, like a it's like called like I think it's like contact inhibition where cancer cells lose contact inhibition. So if they keep growing, growing, growing, growing, growing, they don't respect boundaries and they can even overgrow like whatever thing that's supposed to like sort of like keep them together. So Merlin is kind of involved in that in that process. And again, you may not necessarily see this on the USM Lism just throwing it in here. So again, just to give you like some kind of scaffold to memorize these concepts. Because I know this unfortunately is probably one of my more info denser podcasts. But again, I promise you the time you spend learning this thing will be very, very useful for you on all your USML exams, especially again step one and step two seeking. And then what if you get a question about a patient that has like you know pusher for some ass and they tell you that this patient has a big give you like a hematocrate and it's like 60%. Under those circumstances, I hope you're thinking about like VHL, Von Hippolindau. Von Hippolindau, the big thing you want to keep in mind here is that it's a chromosome three problem, right? It's a chromosome three problem.

They have a mutation in like the VHL gene. And the main problem here is that VHL it's like that protein actually quotes for essentially it's involving the process of ubiquity meeting proteins that make you like that cause like growth and proliferation of of cells. So if you have a mutation in VHL and again it's a disomodominant inheritance chromosome three, you will not be able to tag because the way you destroy things in the body is you tag them with with ubiquity. So if you are not able to tag those growth signals with ubiquity, the process for a longer period of time, you have proliferation of things and obviously cancers can be the outgrowth of those. So what are the classic cancers that you find in people with a VHL? People with VHL they tend to get hemangioblastomas in the brain, usually like in the posterior force and the cerebellum. I remember that hemangioblastomas can produce epo in a pernioplastic a fashion. So those people tend to have like elevated hematocrate. People with VHL they can also get like like cysts in the liver and like cysts in the pancreas. That's again a weird high-yield thing you want to stock in somewhere at the back of your mind. And then they can also get like bilateral renon cell carcinomas. That one is especially high-yields too. That one is especially high-yields to remember for NVME exams. And again like you may ask yourself why do they have this hemangioblastoma? A hemangioblastoma is essentially like a vascular tumor.

The thing is there is this transcription factor that essentially controls the production of blood vessels. It's called like hipone alpha. It's called like hypoxia inducible factor one alpha. The thing is the thing that puts ubiquity in on hipone alpha to target its degradation in the cell is VHL. So again if you have that VHL mutation you will not be able to downregulate the activity of hipone alpha. And you have like a ton of angiogenesis and you have a lot of again problems with like vascular-based tumors. Now what if they give you a question about I guess I will just mention it instead of making it in a case but I guess you get a question about a person that has like multiple polyps in the in the colon or whatever. Think about FAP right? So like familial adenomatosa polyposis. Remember that it's a lot of some more dominant inheritance. Those people should start getting colonoscopies like in the teenage years like before the age of 20 and remember like some off-shoots disorders like a torco syndrome where those people can have like metroloblastomas and a pregnant syndrome where those people can have like soft tissue ostiumus. And then what if they give you a question about a kid excuse me that you know has like gout. I mean you should you see gout in older people not in kids but you see a kid with gout and they tell you that this kid you know choose off his fingers and his toes and all that stuff like essentially like self-mutility and a behavior.

I wonder those circumstances think about like lesh nihan syndrome. Lesh nihan syndrome it was actually discovered at my alma mater where I went to med school but essentially they have like a deficiency of an enzyme called a HGPRT. HGPRT means hyposanthin guanine. Do I think HGPRT? Yes. hyposanthin guanine falls for a busola transferase. So they will have problems with like the purine salvage pathway. So if they have those problems essentially the thing that will happen is they will begin to make a ton of uric acid so they can have gout and some of the things that accumulate are kind of like toxic to neurons. So those people tend to get like very bad intellectual disability and they also tend to get a again a lot of like self-mutility in a behavior. So that's kind of like the big way lesh nihan syndrome presents and really these ex-linked recessive disorders. I did hear right you should remember that you would only find them in male sonnumbia me exams right that's kind of like a big thing you want to keep in mind. So if for example like you have like a guy that has this disorder then his sons cannot get it right because he cannot pass off his excromosome to his son. He only passes off his white chromosome to his son but his daughters will be like carriers right so that's something to keep in mind. And if you have like a daughter of a person that has like an ex-linked disorder the daughter will likely again be like a carrier right or they may like be completely normal.

And again just I'm just seeing this for purposes of those like ponex square like not really ponex square like those like forgetting what they're called those like circles and squares that your friends at the mbme draw to try to get you to figure out like the method of inheritance of a disorder. Again these are just kind of ways you can figure those things out but I will talk about that in a in a different podcast. So lesh nihan syndrome self-medility behavior that's kind of like the big thing you want to know. Lesh I think he was an attending physician. My hand I think he was a met student at Hopkins back in the day. I mean imagine a met student you essentially discovering these things kind of makes you feel like an underachiever sometimes. Okay now some other high or the ex-linked recessive disorders you want to keep at the back of your mind. You want to remember a phrygix ataxia right so phrygix ataxia it's one of these a trinucleothide repeat disorders I take that back I apologize phrygix ataxia is actually inheritance or a more recessive fashion that's where like the kids have like a taxia and it's like a gAA trinucleothide repeat problem. I mean in fact let's take a small sidebar because I don't want to forget.

The trinucleothide repeat disorders be a very high you to know for step two and for step one and the thing is in general almost as a general rule the trinucleothide repeat disorders are inherited in an orzomo dominant fashion but there are some exceptions so those exceptions are high you for exams.

So the four big ones you probably want to commit to memory the first one is a myotonic dystrophy the classic without presenting is they'll tell you about like a kid visiting a physician and then the physician has trouble like releasing his grip from the kid's hands or from the patient's hands another way may present him maybe like a young guy that has like early balding right like you see a present that's balding their 20s think about myotonic dystrophy with that the trinucleothide repeat here is like CTG and again it's orzomo dominant inheritance and the gene that's mutated is like the dmpk 1 gene that's something high you do you want to keep at the back of your mind and then another disorder that's a trinucleothide repeat disorder is like the classic content tense it's a chromosome 4 defect right and remember that the trinucleothide repeat is CHG right then again these people have like a you know like choriform movements and like dementia and like inappropriate behavior and they'll tell you that oh maybe that died of like some weight gain at 50 and then the kid died is exhibiting symptoms at 40 that's essentially like illustrating the genetic principle of anticipation um yeah illustrating the genetic principle of anticipation so it's like the disease comes up earlier and in like worser form at the age of like in a younger age right that's a that's a generic anticipation it's a common principle that's found with these are trinucleothide repeat disorders and I just said that in haunting tense you have choriform movements the thing is on your mba exams there are three things or four things you want to keep at the back of your mind if you ever see mention of choriform movements let me just sort of put it all together for you here one is um haunting tense as I already mentioned another one is the cedenham's courier that you'll find in people that have um rheumatic fever a

nother thing that can cause um choriform movements is like if a person has like a lesion at the subthalamic nucleus so they have like a contralateral a hemibalismus that's another example of a choriform disorder and then another weird one is something called pandas so like I think it stands for like pediatric autoimmune neuropsych disorder associated with group B strap um so pandas for short do essentially describe a person that has had like you know upper respiratory infection like a year or two or go whatever and then they tell you that uh like maybe like two one or two years later they have like choriform movements and like just weird things that it's like an autoimmune phenomenon uh think about that with choriform movements um that's something they love to test on the pediatric cell exam and also on step two ck and then I don't know if this necessarily qualifies for choriform movements is more like myoclonus but neuroblastoma people that have neuroblastoma remember it's like the mass flank mass in a kid you can also shop in the posterior medias thinam it crosses the midline and it contains the calcifications um those people tend to have something called like obso clonus and myoclonus as syndrome like dancing eyes and like dancing feet so I don't know if that uh kind of helps you there uh the only other things I guess again this is a sidebar conversation it just again kind of dropped in my mind so I want to like I guess throw it in here um the other things that you may see with myoclonus on an mbmi uh the first one is a chrysfolia acopa disease remember it's like a rapidly progressive dementia uh those people tend to have myoclonus remember that it's a pre-earned problem right so uh and in the csf they will have like elevated levels of the protein of 1433 and then the other myoclonus related disorder is a serotonin syndrome right myoclonus is a pretty pathonomonic

feature in a serotonin syndrome okay so let's get back to a topic at hand so um I at some point was talking about a trinocluthyripe disorder so I really talked about hunt intents seizure repeats I talked about um and I mean hunt intents you cannot really treat it with like dopamine antagonist like alopere doll or like tetrabenazine so I've talked about hunt intents or the zomodominant inheritance I've talked about my atomic dystrophy CTG trinocluthyripeats or the zomodominant inheritance um fragilex syndrome right so they'll describe a kid with like big everything like big ears big testicles long face think about fragilex with that um those kids tend to have like a lot of like autism related problems a lot of like ADHD related problems and unlike the other trinocluthyripe disorder that I inherited in an autosomodominant fashion fragilex syndrome is actually in herethin and an x-linked dominant fashion um so and the trinocluthyripe is a CGG repeat okay so that's something I want to keep in mind basically there are only two x-linked dominant disorders that you can see tested on an mbme one is outport syndrome that's the collagen four defects so like defecting like COL4 A5 the other one is uh is a fragilex syndrome and then the last trinocluthyripe disorder that's commonly tested on mbme is a fridgetsy taxia it's like a gAA trinocluthyripeats but unlike the other trinocluthyripe repeat disorders that I inherit in an in an autosomodominant fashion it's actually inherited in an um autosomodorescessive fashion okay so that's something high you'd want to keep at the back of your mind for example and the predominant symptom those people have is is literally itaxia okay um and then some other high-iodx-linked recessive things you want to keep in mind right if they give you a question about a kid getting like recurring like viral and fungal infections and then they tell you that

this kid has like hypopigmented skin and this kid has like low platelets I would really hope on that those circumstances you're thinking about whiskot ordrich syndrome okay whiskot ordrich syndrome uh remember like the big things they have like a t-cell problem right so they have like viral and fungal infections they have eczema that's why I was describing the hypopigmented skin and they also have like thrombocytopenia again remember whiskot ordrich was shopping guys on tests not in ladies okay not in ladies uh because it's an ex-linked recessive disorder just in general this is not always from what in general the major high-yield immunodeficiency disorders inherited in an auto so in an ex-linked recessive fashion another key one is like cgd right so the again any deep age oxidies and deficiency remember um cgd you treated with interferonogama um those interference and what they treat a high-yield to know for mbim exams right so um the big ones you probably want to remember is like interferon alpha again I promise I'll get back to cgd but again I'm trying to again just uh integrate as many concepts as possible with this podcast interferon alpha is used to treat hep C uh the way I remember that is like hep CIA right like the government agency that fight-scrime hep CIA so hep C interferon alpha interferon beta is used to treat uh multiple sclerosis uh the way I remember that is like biomedical sciences so like BMS so like interferon beta for ms and then interferon gamma is used to treat cgd so cgd again ex-linked recessive the classic presentation on mbm is they will describe a kid that's you know uh having like recurrent like infections with like stuff or else and they will especially have like stuff or else abscesses okay stuff or else abscesses or like lymphadenopathy where the isolate stuff or else if you see that think about cgd chronic agronolomatosis disease and

the enzyme that's deficient is like any deep age oxidies and I mean there is a there are two ways you can diagnose this right so you can do like the uh the nitro blue test-resolium test that's one thing the test but there is a newer the sort there's a newer test that is more high-yout and more commonly tested it's called like the rodamine or a mean whatever testing it's like dihydro rodamine like I think it's like dihy dror d-a-m-i-n-e I'll just look this up online but it's a test it's like a better test for the diagnosis of uh for the diagnosis of cgd and then another ex-linked recessive high-youthing one of our members um is uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh um uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh uh u

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Maternal non-disjunction (non-disjunction during maternal meiosis).

Endocardial cushion defects.

Elevated phenylacetate and unique musty odor due to phenylalanine buildup.

Klinefelter syndrome (47,XXY).

Aortic root dilation or dissection, due to defects in elastic fiber integrity.

Tay-Sachs disease (due to GM2 ganglioside accumulation).

Maternal non-disjunction.

Trisomy 21 (Down Syndrome).

Prominent occiput, overlapping digits, and rocker bottom feet.

WAGR syndrome (or Beckwith-Wiedemann Syndrome).

Primary amenorrhea, streak ovaries, short stature, and webbed neck.

Pompe disease (Type II Glycogen Storage Disease).

Hexosaminidase A.

Chediak-Higashi syndrome (or primary immunodeficiency).

Marfan has lenses dislocated up and out; Homocystinuria has lenses dislocated down and in.

Maternal non-disjunction.

Trisomy 21 (Down Syndrome).

Prominent occiput, overlapping digits, and rocker bottom feet.

WAGR syndrome (or Beckwith-Wiedemann Syndrome).

Primary amenorrhea, streak ovaries, short stature, and webbed neck.

Pompe disease (Type II Glycogen Storage Disease).

Hexosaminidase A.

Chediak-Higashi syndrome (or primary immunodeficiency).

Marfan has lenses dislocated up and out; Homocystinuria has lenses dislocated down and in.