DIP Episode 162 - ABP Peds Boards Series 1 (Metabolic Diseases)

Okay, welcome. My name is Divine, I am a resident. This is episode 162 of the Divine Intervention Podcasts and in this podcast I was starting a new series for the Pediatrics of Board exams. So this will be Series 1 and I'm going to be focused primarily on Pediatrics and Metabolic Disorders. So let's go ahead and jump right into it. So really these are Peds Metabolic Disorders I would say that the I mean they're kind of complicated kind of annoying to learn and all that but unfortunately they are kind of high up to know for the Peds boards and the key thing you want to know about each of these disorders is you want to know the unique defining feature because again many of these disorders many of them cause vomit and diarrhea and lethargy bloody bloody blood but if you know the unique defining features then you can typically spot them a pretty easily on exams.

They don't like they don't make them the only thing that makes these things annoying to learn is there's so many of them but again if you learn the unique defining feature right then things kind of begin to click for you and the thing is I will try to be like very emphatic with with defining features and we're possible I'll try to explain like some light pathophysiology and I know people studying for the Peds boards and not necessarily thinking in step one terms because really many of these metabolic disorders if you really go down and dig deep many of them actually have like pathophys behind a lot of the presentations but I won't go I won't go like a supreme depth on those if you're interested in any of those you can I guess reach out to me I can always try to explain but but yes in general you just want to learn the unique defining features and the thing is many of these pediatric metabolic disorders right like most of them are truly in inheritated and autosomal recessive fashion so that's kind of a good thing so you don't have to let keep remembering like oh this is a heritet in this and that no no no no you just need to remember for the most part they're in heritet in an autosomal recessive fashion the exceptions to this role right and it probably makes sense to learn those exceptions but trust me it's better to learn the exceptions and then you know that every other thing is autosomal recessive right so for example like some of them are in heritet like in an exlinked recessive fashion and and one way I remember which one is which especially those in heritet in an exlinked recessive fashion I remember that with the nomonic halo M so H a L O and then like a hyphen an M right so the the H is for like hunter syndrome and remember there's this probably step one nomonic you learn back in the day that a hunter max an X spot right so exlinked recessive and then the east

stands for adrenal lukodistrophy there is a kind of a general lukodistrophy that's in heritet in an an exlinked recessive fashion and then the L stands for lish nighend syndrome that was actually discovered at my alma mater Johns Hopkins and was discovered by like an attending a medical student that kind of makes you think how how much you have to like work harder to achieve in life and if I met students already discovering stuff like this right but that was pretty impressive I feel like but yes lish nighend syndrome right like a kid with like self-mutilation and gout right it's beginning to be in a boy these disorders will likely be in boys because they are exlinked recessive right and then the O stands for its only thing transcabamolize deficiency I remember OTC deficiencies classic in the irrepsi-co really for the most part every other irrepsi-co deficit that you need to know is inherited in an autosomal recessive fashion with the exception of the only thing transcabamolize deficiency and then the M stands for mankeys disease right remember some people call it like the kinky hair disease where people have like issues with copper metabolism I'll talk about that later and really for the most part some of these disorders right may not necessarily some but many of these disorders they actually arise from just having like enzyme defects right and the thing is if an enzyme doesn't work right then bad stuff will accumulate the thing is if the stuff that accumulates is not terrible right then you probably you know probably won't care much about it only problem is some of the stuff many times in these diseases the stuff that accumulates is typically like really bad right so when you actually like accumulating bloodstreaming like yeah don't do you too many good things right and especially like when it accumulates like in the brain or in the spinal cord or like in the periphe

ral blood or like in the liver when the kidneys right causes a lot of problems right and really for the most part it's like amino acids and sugars that tend to accumulate and I guess some weird metabolites are here and there which again we'll kind of talk about and really for the most part these kids when they're born they're usually pretty fine but once they get an exposure to something you notice that oh within you know a couple hours or days or months or years after birth and just weird things just that happening like they just become lethargic they have a padosplenomegaly and all that that's your gonna tip of the dealing with some kind of an inborn era of metabolism right and really for the most parts the way you detect these things is you do like a newborn screen like an expanded newborn screen and obviously right if you want to treat these things you try to give something that can I guess prevent like the like can sort of break down these bad things that are accumulating or you can try to do some kind of dietary restriction that contains the bad thing you don't want to accumulating these people right and many times as well you also want to like you know restrict these people's like a calorie deficiency right so you'll probably want these kids that have these disorders to have like very limited periods of fasting because when you fast you begin to break down some of these nasty things that can then accumulate and then cause symptoms so those are kind of like the big picture things you want to keep at the back of your mind with these metabolic disorders okay so let's go ahead and jump to the first one right so whatever they give you a question about a kid you know that has like like autism like problems has like seizures has like abinism so like skin hypopigmentation has like a musty order what diagnosis are you thinking about when I would hope you're thinking abo

ut a PKU right so PKU phenokitonuria right it's like a deficiency and you can actually get it in one of two ways right so one we can get it is by having a deficiency of an enzyme known as phenol alanine hydroxylase right so pH remember that's the enzyme that helps you convert a phenol alanine to tyrosine so typically if you do a newborn screen for these people you notice that they will have like very high levels of a phenol alanine and they will have like very low levels of tyrosine right and the thing is this is classically fine like sometimes because one thing I've noticed with these pediatric board questions is the occasionally give you like ethnicity the ethnicity can usually actually guide you down a certain path right so for example if they describe a you know like metabolic disease in like an Irish person I probably want to think about probably want to think about a PKU because it's pretty common in the in the Irish and like I said on newborn screen you have an atherin alanine you have low levels of tyrosine because again if pH doesn't work right phenol alanine will build up and tyrosine will go down because pH converts phenol alanine to tyrosine and then typically when people do these newborn screens they also tend to check like levels of I guess activity of tetrahydrobiob train so like pH 4 because there are actually some phenotypes of PKU that are associated with like problems with pH 4 and I'll talk about that shortly in a second and really for the most part right these kids that have a PKU right tyrosine because the thing is phenol alanine is an essential amino acid just in general right you get it from the diet right but when people have PKU tyrosine then also becomes an essential amino acid because they have no ability to make tyrosine because pH is offline right and many most times these kids are normal at birth but if you don't treat it by two months y

ou have like irreversible neurological damage right so again classic presentation on the exam should be like a person that has like neuropsychiatric issues right from again like from having like the low dopamine because remember if you go back to like your step one study and I'm not saying to do that but if you were to do that you remember that phenol alanine already is converted to tyrosine and then tyrosine can be converted to L dopa but in this I think known as like tyrosine hydroxylase and then dopade is converted to like dopamine by like dopamine decarboxylase so if you have a deficiency of like something very upstream in that pathway you have a lot of issues making dopamine right so these kids can have like you know like neuropsych issues they have issues like controlling their body temperature they can have like albinism because remember tyrosine remember phenol alanine gives rise to tyrosine and then tyrosine can actually be used to make to make melanin right so if you have like that those melanin you have like loaf if you have like problems again making tyrosine because pH is down then you won't be able to make a melanin right so and then so they can have an albinism and then again this key is tend to have like a musty other and again for the most part you want to treat it before at least the age of two weeks you want to treat it within the first few days of life right so that again they don't have like permanent neurological damage and these kids right hopefully remember that you want to hopefully avoid like diet soda because remember some of the the stuff in diet soda right like some of them can be broken down ultimately to phenol alanine right and sometimes they can give you like these like you know like I don't think of them as nasty questions but I think of them as like ingenious questions where they give you a child and they tell you that oh you know th

is kid has like you notice you do like a newborn screen you notice that the kid has elevated levels of phenol alanine so you adjust the kids diet but you notice that this kid is still developing like SQ Lite of BKU under those circumstances that should really make you think about like a BH4 like tetrahydrobiopterin and metabolism issue causing a pH I mean causing PKU because remember phenol alanine hydroxyl is used as a tetrahydrobiopterin as a cofactor right so that's again one of those weird things you want to keep at the back of your mind so if you see PKU symptoms like if you see PKU symptoms after like yes you know you've done the right thing you've adjusted diets and everything then think about think about a BH4 deficient problems classically that rises because the person has like a mutation in the enzyme known as a tetrahydrobiopterin or reductase so those people have trouble regenerating BH4 right so if you have trouble regenerating BH4 you can have PKU style symptoms and really for the most part the way you treat this PKU right is just modify these people's diets you know you want to give them a diet that's low in phenol alanine actually there's formula believe it although it's very expensive but there's formula that you know has like very low levels almost no phenol alanine in it and for the one where they have issues with my tetrahydrobiopterin like metabolism that they have those kinds of issues you actually want to give them like the BH4 you want to give them BH4 drug is crazy expensive is like a hundred thousand dollars a year super expensive although I know there's some discussion in the works to make like a generic form but I still suspect still be pretty expensive and then these kids right they actually also need like supplementation of a L-dopa right so you actually give them L-dopa remember L-dopa is also used to treat Parkinson's but yes you do give

them L-dopa because again the thing is remember I said that tyrosine is converted to L-dopa by tyrosine hydroxylase tyrosine hydroxylase actually uses BH4 as a cofactor so if a person has like a BH4 metabolic issue it's not just phenol alanine hydroxylase that will be all screwed up tyrosine hydroxylase will also be screwed up right so these people need L-dopa supplementation and then they also need supplementation of something called a 5-hydroxy triptofan because again remember that like the enzyme that makes 5-hydroxy triptofan from triptofan actually does require BH4 as a cofactor as well so those three enzymes that need BH4 as a cofactor you do need to like essentially give things that would reverse like essentially reverse the deficiencies you have with BH4 not being available and one of the classic thing they love to test on the pediatric board exam is remember from mom right let's say she's like a carrier of like whatever like the like the PKU genotype like she's a carrier because remember it's herodin or zomorgocesifation right one thing you want to keep at the back of your mind is she has to be careful right like with her diet because the thing is if for example had kid if she has like very high levels of a phenol alanine that can also affect like the kid in utero right so those kids tend to be more with like small heads so like they have like microcephaly they have like intellectual disability they can get all these congenital heart defects so that's something I want to watch out for because the thing is if you're taking like basically like your kid sees like one and a half times your serum phenol alanine concentration right so again if the kid has a deficiency of phenol alanine hydroxylase let's say mom has like I don't know like a hundred of phenol alanine blood really that would be pretty high from the most seeking the kid will see 150 right so you want

to be careful on that also circumstances and one thing I think I neglected to mention is so I talked about the ex-linked recessive disorders I should also mention right there some disease that I inherited and amitocondrial fascia right those being inherited from mom that's something to keep in mind for the most part they tend to be like like like those the classic two classic things you typically see on the exams with those disorders you'll talk about like lactic acidosis because the mitochondrial doesn't work right so you cannot do this whole electron transport chain business and then in addition to that these kids tend to have like you know like stroke-like episodes and they may have like they may tell you that oh they do biopsy and you notice that you're seeing like ragged red fibers that's like a classic presentation classic presentation on the Pids boards classic presentation on the USML exams from back in the day so again these are all things that you just want to keep in mind for for these tests okay so now what if they give you a question about a kid you know that has like you know like intellectual disability has like downward dislocation of the lens and then they tell you that this kid has had like strokes and like I don't know like let's say like coronary schemia and has all these like neuropsychiatric problems what are you thinking about well I hope you're thinking about a homocysteineria right homocysteineria I remember homocysteineria right cannot you know there are many things that can cause it typically can arise from like a most common new on exams arises from like a CBS deficiency so you just think like this TV station CBS CBS stands for sister thionine bitters and things so it arises from a CBS deficiency although there are many other things that can cause it right if you have like met a methionine synthase deficiency sometimes they put that on exam

s as a MTHFR so if you have like a methionine synthase deficiency or if you have like a deficiency of like vitamin B6 so that's like pyridoxyl phosphate of vitamin D9 that's like full it of vitamin B12 that's like you know a cobalamin deficiency those can all cause a homocysteineria and really for the most part you know you make the diagnosis by establishing that this person has like elevated levels of methionine and homocysteine right that's classically what you would observe in a person that has that has the CBS deficiency as the cause of the homocysteineria I guess I mean if you wanted to like look at other things right like if for example a person had like like an MTHFR deficiency as the cause of the homocysteineria they will have elevated homocysteine with a methionine will actually be low or if for example it was B12 causing their problem they will have elevated homocysteine and they will have like a methionine as a demia right they will have like increase that levels of methomalonic acid those will tell you that okay maybe this is more so before the efficiency causing this person's problems than a than a CBS deficiency and again classic presentation Marthenoid body habit is right kind of like Marfans but remember that people with Marfans tend to have normal intelligence versus people homocysteineria that tend to have an intellectual disability and then in Marfans right in Marfans people tend to have like ectopia lentis where the lens is dislocated upwards but people that have almost system really tend to have like a down downward dislocation of the lens and then these people tend to have like you know like a small but significantly increased risk of a like venus astralmobolic disease right and again the way you treat this for the most part you know give them vitamin B6 you can you know choose a diet low in methionine you can also give them this supplement calle

d like it's like the liver form of like a system between basically it's just that when you give like the system between supplement it essentially promotes the conversion of homocysteine to methionine although there are also some issues with that drug because it can also like maybe cause like for the elevations in homocysteine so you typically only use it when you have like very low levels of homocysteine that you're trying to like decrease and then obviously you also want to maybe give these people like a diet that's low in sulfur because remember that methionine and homocysteine contain a lot of soft hydro groups and is those soft hydro groups that are super reactive and end up causing a lot of problems now what if you get a question about a kid you know that within the first few months of life like develop cirrhosis and this kid has like a type 2 RTA so like they tell you that oh this kid has very low levels of phosphate in the blood or very high levels of phosphate and all these amino acids in the urine or they give you a question about a kid that has like hepato cellulocarcinoma or detail you that oh this kid is Canadian right like from Quebec Canada I hope I pronounced that right or they tell you that oh you have a kid that the urine smells like cabbage if you see all those things I would really hope you're thinking about a type 1 Tyrosinemia okay type 1 tyrosinemia really for the most part the thing that kind of causes many of the problems is you have a deficiency that ends I'm known as a fumerial acidity tyrosilis the way I just think of it is I just think of it as FAH so fumerial acidity hydroxylis right and again the presentation you can't miss it on the example it's pretty classic like you have liver problems like hepato cellulocarcinoma in a kid right that's very unusual right so if you see like a kid with HCC or a kid with a type 2 RTA where they have like

you know like they have a fancony syndrome like presentation where they have like hyperphosphaturia like yes you can see hypophosphatemia right and they have like increased levels of like amino acids in the urine think about think about think about a type 1 tyrosinemia this gives they'll have you know like cirrhosis like early cirrhosis conjugate hyperbular venemia they'll have like a quagulopathy because their liver don't work right so they have like clotting factor problems they also tend to be hypoglycemic right because again gluconeogenesis doesn't work as well and again Canadians urine smells like cabbage or like like butter that's kind of gone bad if you see that think about type 1 tyrosinemia I've noticed in general these amino acid problems they tend to present with like you know like unusual smells like BKU must be ordered type 1 tyrosinemia cabbage smell to the urine and stuff like that so again like I said you have a deficiency in a firm fumerial acidity hydroxylis so there's this thing called a fumerial acidity that will build up right the thing is you want to know the two different names and not strong with me so you actually want to know the two different names of this compound so fumerial acidity is an immune mission exams but another immune mission test is something called a succinyl acetone it's the same thing fumerial acidity is also known as a succinyl acetone the thing is this when you're breaking down a tyrosin fumerial acidity or you know what I'll just call it a succinyl acetone from now because it's kind of like a easier to manage see that but one of the if you're breaking down tyrosin there's like multiple steps one of the final steps in the breakdown of tyrosin involves like the breakdown of something called succinyl acetone right so the thing is if you have a deficiency in the enzyme that breaks down succinyl acetone which is again the FAH

a mentioned earlier then succinyl acetone will build up and the thing is it tends to build up like most like in hepatocytes and in like proximal convoluted to be of cells and the thing is succinyl acetone it's very reactive species so because it's reactive it can cause like dnidamage and if cells have dnidamage right those cells on the goypoptosis they die right so that's why these people tend to have like liver problems and keeping problems right and again right if you're having like dnidamage and let's see the cell progresses through that dnidamage and does not fix the dnidamage right that can also tell you why these kids me potentially have hepatocetolocarcinoma and really for the most part the way you treat this you you know give a diet low in tyrosin because again if tyrosin builds if you the more tyrosin you give the more you increase flux through that tyrosin breakdown pathway and then succinyl acetone will build up but other things you want to do right there's this drug known as a netisynone so NITI SI and then none right so netisynone basically inhibits it it's a drug that it's very expensive the thing is it inhibits an enzyme that so maybe let's think of it this way let's say there are six steps in the breakdown of tyrosin right and let's say that the step that you know leads to the formation of soxinol acetone is like step five the thing is you can give this drug netisynone and inhibits like a drug in step two of the breakdown so you don't even build up the succinyl acetone in the first place okay so that's why netisynone works extremely well with this the solder the only problem is when you give a person a netisynone you actually have to monitor their levels of phenol alanine and tyrosin kind of make sure it doesn't build up to like toxic levels because the thing is buying inhibiting this enzyme I mean if you're interested again I think the no enzyme name

is very loyal for exams but the enzyme name is like a hydroxyl phenol pyruvate dioxygenase but basically if you inhibit the enzyme your phenol alanine and tyrosin actually go up right and you don't want to like essentially induce pku in a kid right so you want to measure you know monitor their levels of tyrosin and phenol alanine when they're netisynone so that's again classic presentation of the type one tyrosinemia keep from Canada you're in smells like cabbage hepatocello like a snowman in the kid type two RTA funkony syndrome like presentation liver problems okay that's a classic presentation of type one tyrosinemia and then what did you give your question about a kid that you know seems to have the tell you that during the third trimester like mom like this kid was observed to have like you know multiple hiccups like mom says she has like unusual fetal movement in the third trimester and the tell you that oh after this kid is born this kid keeps having like recurrence seizures having like apnic episodes and this kid just you know needs to be into bed and then this kid is like you know severely and cephalopathic has like all these movement problems intellectual disability just respiratory issues that require intubation I mean if you see that what should you be thinking about well I would hope you're telling me that you're thinking about something called glycin and cephalopathy okay glycin and cephalopathy sometimes it's called like a non-ketotic hyperglycinemia okay not hyperglycinemia okay because the thing is on exams right again this is how can you make an exam hard like just put words that sound similar so look out for the turn right don't choose non-ketotic hyperglycinemia this is non-ketotic hyperglycinemia right so and the video levels of glycin and actually this glycinemia is cephalopathy believe it or not it's actually the second most common amino acid am

inabolic disorder after pkg right so the thing is the deficient the mutation that people have here is you have a defect in like an enzyme complex known as the glycine cleavage system the glycine cleavage system it's basically like an assist is a system of enzymes it has like force subunits if I'm not mistaken that breaks down glycin right so if you have a mutation in the glycine cleavage system you know you'll be able to break down glycin so glycin will build up to like very toxic levels in like body fluids in the CSF the big one I wanted to remember is that the glycine builds up to toxic levels in the CSF okay and again you just want to be careful notice I specifically called this non-ketotic hyperglycinemia the reason I called it a non-ketotic hyperglycinemia is because there are actually some other disorders that I'll talk about probably in a follow-up podcast that associated with like a ketotic hyperglycinemia right so that's one thing you want to keep at the back of your mind and the diagnostic test right you know you check levels of glycin in the CSF you'll be like you check levels of glycin in the CSF and in the plasma the levels like you almost measured as a ratio the ratio of glycin in the CSF will be much higher than the glycin in the plasma that tells you that okay this person has this glycine and Sephalopathy remember I just said that oh that people can have a a ketotic hyperglycinemia the thing is in ketotic hyperglycinemia people may have a little bit of levels of glycin but the thing is the ratio between like the CSF glycin and the and the plasma glycin will be like relatively normal and really for the most part the way you treat this glycin a glycin as a phyllopathy is you can essentially you know give the kids like sodium benzoate the sodium benzoate will bind up a glycin and convert it to hyperglycin and then that can be safely excreted and then you

can also give that Schrommeth or fan although to be honest like this disease is not really well understood but for the most part people think that glycin acting on NMG receptors causes a many of the like neurological symptoms that these kids have so if you give Dectromythorfen is like an NMG receptor antagonist so that can help with like preventing glycin from binding and can hopefully help on that those circumstances and with this disease I mean it's terrible right most times like by the age of three like 90 days of life most of the boys with this disorder are dead girls their life expectancy is even worse they really did within like the first 30 days of life so you know it's a pretty terrible disorder but thankfully it's it's pretty rare but I mean it's not something you would wish on anyone now I think the last group of disorders are probably talk about in this podcast because again I want to really keep this on the like you know like 40 minutes if I can is at the U.S.

cycle defects right so if you're a pitch resident I mean probably from step one probably the only U.S. cycle thing you remember is like if you remember any at all is a OTC deficiency like anything transcapa release deficiency unfortunately that's not enough for for the pizza boards for the pizza boards they do actually want you to know the different uh U.S. cycle defacers about like split about mind of them the thing I would encourage you to focus on because again many of these disorders the presentation is the same right although some of them have like some unique things but I will tell you that the thing that will be the clincher on your exam that will help you get the correct answer is knowing what is up and what is down like almost all these disorders have like something that is uniquely elevated and uniquely decreased if you can keep those things at the back of your mind then you should be golden for these are U.S. cycle disorders but for the most part right for the U.S.

cycle disorders the classic presentation is you know they'll give you a kid that you know within the first few days of life is fine but once this gets that's like feeding like getting food of any sort this kid you know has like like a very poor arousal like the hotel you know the brain's try to weak the skin up to to feed but this is not very responsive right and this kid we have you know like hyperventilation so they can have like a respiratory or calosis because again ammonia is kind of toxic to the brain these kids tend to be hypothermic remember the way I kind of think about it is if you remember from med school taking care of a person that has like liver disease people like liver problems like cirrhosis they tend to be like hypothermic right and the ureth cycle operates in the liver right so that may give you some hints as to why these people may be hypothermic although that's not really the reason it's more related to the ammonia toxic effects in the brain and then typically right you do a newborn screen notice that these people have like very high levels of ammonia so they have like a hyper ammonia the agglutamine the agglutamine is also elevated because glutamine is one of the feedstocks for the ureth cycle and again classically these kids tend to have a respiratory or calosis right and really for the most part the way you detect these again like I said you do a newborn screen you check ammonia levels you check glutamine levels you check levels of like citrulline you check levels of arginine you check like levels of like arotic acid in the urine because the thing is different permutations of what is elevated or decreased will tell you that oh you're dealing with one disorder versus the other so and you may say like divine why does this ammonia cause any problems I mean it's just ammonia well it's not just well I mean it's just ammonia but the problem is ammoni

a right crosses the blood brain barrier pretty easily right and when it crosses the blood brain barrier lots of celluline astrocytes right and the thing is when the ammonia settles in astrocytes ammonia is very reactive and I mean it's very osmotic right so it draws a lot of water into those astrocytes so those astrocytes swell and as the astrocytes swell that can actually begin to cause like increase the intracranial pressures believe it or not they actually like cases of kids that have had like a brain herniation and died from this disorder right so those increase intracranial pressures remember right those increase intracranial pressures the brain will try to say oh crap my intracranial pressures are high let me try to like lower my ICP by hyperventilating right I mean if you've taken care of anyone in the hospital with like elevated ICP from like an ischemic stroke or whatever you raise that percentage respiratory 12 on the vet right so the thing is many times when people have these problems right the astrocytes swell that causes increased ICP they begin to hyperventilate it's that hyperventilation that ultimately causes the ultimately causes the respiratory alkalosis right so those are again classic presentations kid you know first release of life kid is not very arausable to feed has hyperventilation and again I've explained the mechanism behind that has hypothermia the blood pH will be very high so be more than like 7.45 because they have they have like the respiratory alkalosis right or they may give you like AB Gs and you see like a profoundly depressed PCO2 if you see that again you want to think about some kind of a ureth cycle of problem and again I've talked about the different labs that you check and some key things you want to keep in mind is I guess in terms of treatment right for treatment you can actually give you can actually give something called a

phenylabularite right so you can't be very good the thing is it essentially binds ammonia right you can bind ammonia you can bind glutamine and then you can feed up right and then the thing is you also tend to want to supplement like arginine and citrullin in the diet because by giving arginine and citrullin you can make like make the ureth cycle work better because the thing is arginine and citrullin the body taps them from other pathways to use in the ureth cycle so typically for these kids you know you tend to supplement like arginine and citrullin and then you also you know if a person has like you know very severely elevated ammonia levels obviously you you know you go ahead and do dialysis under those circumstances and then also for these kids you also want you know to increase your caloric intake because think about it really if you have a ureth cycle problem you have issues metabolizing protein right metabolizing ammonia and all that stuff so the thing is you essentially want to decrease the instances where these kids would need the ureth cycles to work right so for these kids you want to give them like you know very rich carbohydrate diet because if they're essentially not in a fasting state then they will essentially never break down muscle right and maybe like you know participating in marathons may not be the smartest idea for these kids because again right you break down muscle and then you need your ureth cycle under those circumstances and then obviously you also want to restrict protein in these in these kids diets so what are the big ones right so I think the first two I'll just kind of discuss them together like the first one is like CPS1 deficiency so like a cabamol phosphide is in that there's one deficiency and then the second one is like Nags deficiency people call it like anacidoblutamate deficiency really for the most part of the symptoms are a

gain a ureth cycle symptoms which I again have already talked about in CPS1 deficiency these people they have a deficiency of a cabamol phosphate that's in these one right and because they have that again they'll have hyperamonemia so their ammonia levels will be elevated but every other thing will be low they'll have like low levels of erotic acid because the thing is already acid is made from cabamol phosphate so if you have a deficiency of CPS1 you're not going to be able to make cabamol phosphate if you can make cabamol phosphate your erotic acid will be low right so these people tend to have like you know like hyperamonemia but every other thing is low erotic acid low citrullin, low arginine again it's what is high what is low now will tell you what ureth cycle or defector you're dealing with for the most part on exams so that's again a very high-ealth thing you want to keep at the back of your mind so that's really what obtained in CPS1 deficiency Nags deficiency is like literally the same thing like anacidoblutamate synthetheza deficiency the thing is if you look at the ureth cycle right so CPS1 is kind of like the reclinitin enzyme of the ureth cycle maybe not so I think it's OTC but CPS1 actually I take that back I'm almost certain CPS1 is that but again that's not necessary for the PI Dsports different audience here but CPS1 is an important is the first enzyme of the ureth cycle right the thing is CPS1 uses anacidoblutamate as a cofactor right so the thing is anacidoblutamate is made by an enzyme known as anacidoblutamate synthetheza so if you have a deficiency of anacidoblutamate synthetheza so like Nags many people call like Nags deficiency then you can produce anacidoblutamate then CPS1 doesn't work right and then you're in trouble right and again the presentation of these things is exactly the same right like they'll have like elevated ammonia but low cit

rullin low or radicacid low archanine so it may say okay define how do I differentiate between these two things well two things you can use right so one is you do like the any testing right because people with Nags deficiency they have to tend to have like issues with like the long arm of a churnosum 17 people CPS1 deficiency they basically you all observe different gene defects causing those two disorders and then one of the classic thing that shows up on exams with with a Nags deficiency you can actually treat it with a drug known as like a carglemic acid the thing is carglemic acid is like a structural structural analog of anacidoblutamate so by giving anacidoblutamate you're essentially giving what they're missing you're like saying you know what I'm not gonna use a Nags anymore or just give you the cofactor so it tends to help somewhat in this disorder although again carglemic acid is extremely expensive so that's what I will say about the first two the next one right is like OTC deficiency this one will classically shop in a boy on exams remember OTC was one of those remember it was the O in the Halo M the monica I talked about earlier so it will likely shop in a guy on tests although the thing is female carriers because that have this a disease they can also get like some symptoms especially when they're like very sick like when they're like septic or whatever so but for the most part like maybe like 99% of the people you see with OTC deficiency on your peat's boards there'll be guys right and again they'll have hypermonemia but here's a key difference they will also have elevated levels of erotic acid right because OTC only think trans cabamolis converts like cabamol phosphates to like other stuff right so the thing is if OTC is deficient right then you'll be able to convert cabamol phosphates to other stuff so cabamol phosphates will build up and then you'll

leave the mitochondria going to the cytosol and then you'll be meeting to erotic acid so if you see a present that has a urethyl defect and you have elevated levels of ammonia and erotic acid but every other thing is low like low arginine low so like low arginine low citrulline think about an OTC deficiency and again the presentation is exactly like what I've talked about for like the general classic presentation of urethyl de-sortars and then the next one I'll talk about is like a type 1 citrullinemia right so type 1 citrullinemia the reason I'm saying type 1 is if there's a type 1 citrullinemia then you should also stanchorism that there's such a thing as a type 2 citrullinemia right so a type 1 citrullinemia it's deficiency in an enzyme known as a arginino-soxanita synthetize there's an amount of people use for this it's kind of like rescuing but like ass you know like you know like a person's ass like ASS like ass deficiency so when you have a deficiency of ass then you can have like this a urethyl problem called a type 1 citrullinemia again the big big thing you want to remember here is what builds because the thing is it's like think of the urethyl symptoms as a script like the lethargy porousel and everything you'll give you all the like literally the same presentation for all of them but again you'll give you labs and then that's what clinches the diagnosis right so people that have the type 1 citrullinemia they have elevated levels of ammonia and they have elevated levels of sexually right because they will have the elevated levels of sexually because again aginino-soxanita synthetize right as for short kind of funny saying that but anyway but when ass doesn't work as well as it should right then citrullin will build up right but these people have low levels of arginino so remember I said in OTC deficiency you have hyperamonemia you have elevated levels of ar

achoc acid both the arginin and citrullin and low and then I said in CPS1 on max deficiency you have hyperamonemia whatever the thing is low arachoc acid arginin citrullin all along right but now I'm saying in type 1 citrullinemia you have like elevated levels of ammonia so you have you have hyperamonemia but you also have elevated levels of sexually right the arginine levels are low okay so again you see that there are all different permutations of of all these things the next big one and one thing I will say about type 1 citrullinemia that may help you on the example is the symptoms tend to study in childhood right contrast this with type 2 citrullinemia that I'll talk about in a bit with the symptoms tend to start in a study in adulthood in fact I think you know maybe it may make sense to talk about type 2 citrullinemia like right now I mean like the type 2 citrullinemia for the most part starts in adulthood it arises from like a deficiency in a name I known as a citrullinemia right and again for the most part it will present with like liver problems in adults really can show up in kids as like a new needle hepatitis but really for the most part think of type 1 citrullinemia as a as a kid problem right and then think of type 2 citrullinemia as an adult problem and a nice way to remember which is which is I just tell myself that you've got to be a kid first so that's type 1 before you become an adult that's type 2 okay so that's a nice way to sort of keep those things as straight in your mind then the next year cycle the sort of talk about is this the sort of known as ageninosuxinita aciduria okay so ageninosuxinita aciduria the big big thing that you want to keep here keep your mind here is that these people they will have elevated levels of ammonia they will have elevated levels of citrullin they will have no levels of arginins you see divine come on how am I goin

g to differentiate this from like the type 1 citrullinemia because those are exactly the same laps in type 1 citrullinemia like high ammonia high citrullin low arginine here's the kicker people that have ageninosuxinica aciduria they have high levels of ageninosuxinita so if you see elevated levels of ageninosuxinita then your diagnosis on your peds boards should be ageninosuxinita succinica aciduria and really the enzyme that's a deficient here is ageninosuxinita lies that's like the classic enzyme that's deficient the thing is this the solder presents just like any urea cycle defect but here is one classic thing that may help you like tell you that oh yeah this is what I'm dealing with on the test they can show you like a picture of like a person's hair and the hair will have like these like broken shafts and you have like these like little modules I'll encourage you to look up a picture of it I think it's called a trichorrexis nodosa so not polyarrides nodosa not erythema nodosa trichorrexis nodosa it's like a like a particular hair problem just look up a picture of this online that's like classic classic classic presentation with ageninosuxinita aciduria the mechanism behind those hair findings remember you kind of need like appropriate protein function because your hair uses a lot of protein but I'm not gonna say any more than that because again that's not something that's relevant for your for your for your exam and the next one I'll talk about is I promise this will be over soon some put out of your pain the next one is argininemia right so argininemia right this one is easy to deficiency of the enzyme arginase um one key thing actually you want to keep at the back of your mind here is in this disorder this is the only disorder at least you're a cycle the disorder that you will that you'll see on your exams that has an elevation in arginin okay remember every o

ther thing has that like low arginin low arginin low arginin and I will summarize like which is high which is ravine just to again sort of put everything together for you both in argininemia these people have like high arginine for the most part the ammonia tends to be normal yeah it could be elevated in some people but that's extremely rare for the most part the ammonia tends to be tends to be normal right the big thing you want to keep at the back of your mind here is it's an arginase deficiency and these people tend to have like prominent muscle findings right so you'll have like a spastic like quadriplegia so like they'll be paralyzing the operandoid extremities um and the thing is it's progressive so let's say they may have you know like one small muscle group that's affected at birth but as they keep progressing through life more and more muscles get affected until they get like a spastic quadriplegia contrast is a cerebral palsy right that's like more like you know cerebral palsy by definition doesn't progress right it's kind of like static so that's one way to differentiate those two on tests and again they'll usually give you a lapse on exams and then the last I guess one of the last of the disorders I want to talk about now there's this uh ureth cycle defect called triple hitches syndrome it's like hyper onythemia hyper ammonemia homosetrillionemia syndrome just remember it as triple hitch syndrome I wish other people people use the other name it's it's like sometimes it's called like an anything translocase deficiency um basically only thing translocase translocase means it transports things right so it moves like only thing to the mitochondria so that I can participate in the ureth cycle um so the thing is if you have a mutation in this mitochondrial transporter you won't be able to move anything into the mitochondria for the ureth cycle so you have ureth

cycle uh style problems uh these people the big things you want to keep in mind is they'll have elevated levels of ammonia and they'll have like elevated levels of anything and they'll have elevated levels of homosetrillion if you see that your diagnosis is done uh it's a triple hitch a triple hitch syndrome and then the last one I'll talk about is uh this thing called a lpi syndrome uh p it's like a lysinoric protein intolerance basically it's a problem with a transporter that you find out the proximal convoluted tubule and in the small intestine so the thing is um the classic presentation and the pay attention here right you'll describe a kid that you know was been fine you know for the first like six months of life and this testy the kid was exclusively breastfed for that period and then the tale is that oh you know this kid was recently wind from breastfeeding and then you notice that man this kid was wind from breastfeeding this kid study having like a lot of vomiting diarrhea a pardostelomagaly um like osteoporosis like uh pulmonary problems like intestine shown ammonia uh glomerulina fritis right so like hematuria it's almost like a post-infection glomerulina fritis a picture um or do you have like recurrent infections um or they have like osteoporosis if you see all those things you really want to think about lpi right so again lysinoric or protein intolerance it's a problem with like again like I said a transporter so you have issues like reabsorbing like an ornithine lysine and uh arginine the way I just remember like what's going on here is if any of you are from like new orlins right so like nola just remove the n um so just remember ola so like an ola like transporter defect um these people will help you put a reabsorbed ornithine lysine and arginine uh in the urine right so obviously if you're doing diagnostic testing they'll have like very high levels o

f ornithine lysine and arginine in the urine um um so because remember orging uh ornithine and arginine are required right for for the urethicule to work well so if you are not reabsorbing these things the urethicule works so well so you have like signs and symptoms of of a urethicula issues and again for the most part you will treat this with citrullin again by giving citrullin you know you kind of like spurs of the urethicule and uh begins to work a little better but again it's not like perfect treatment or anything like that so I think I'm going to go ahead and stop here um as I do at the end of every podcast um I do offer a titrern for many exams right so if you have any friends or buddies or colleagues or siblings I need titrern for step one to ck to cs step three um the the preclinical uh metrical exams 30 a show for exams or you know medicine residents that need children for the medicine in treating exam the medicine boards or you have a you know a peed's resident that needs to do for the pediatric boards um I do offer titrern for all those things um and then um I have these booster courses offer for the u sml exams it's like a 20-hour booster course for step one it's a 10-hour booster course for step two ck and step three essentially in those uh booster courses um typically something you do like in the last week of your prep or when you feel like your knowledge base is pretty good um I use a very sharp period of time and I integrate like most of the high-yield things that I tested on the exam in a Q&A format we sort of walk through those and then um I also offer like longitudinal tutoring where if you if you're like the first or second-year med student or your third-year med i teacher it for like your block exams or your shelf exams and then at the same time i teacher it for you like upcoming on u sml exam and by doing that uh every essentially everyone I've d

one that with has been like well wildly successful on tests uh because um it's like by time the hiday of the day it appears they tend to be like super super ready for the exams and then if you have like a college buddy that needs to do it for like general chemistry or gynecchemistry physics biochemistry histology physiology offer titrern for all those things as well and then if you're a med student applying to a residency so like an iris application or a college student applying to med school so like an amca's application I don't know if I guess like one of one like advice you know coaching like yes you can call it consulting for those so things like personal statement track letters um it didn't apply to the students more interviews I mean I've I've worked with tons and tons of students that have applied for both of these things and I've also been on an admissions committee at a top two med school for like a year so I have again a ton of experience out with these uh issues so if you need any help with any of those things either reach out to me through the website or you can send me an email at divine intervention podcasts with an s at gmail.com so I wish you a wonderful weekend have a great rest of your day god bless you I'll see you in the next podcast thank you

Musty odor, elevated phenylalanine, and low tyrosine.

Citrullinemia Type I (Argininosuccinate synthetase deficiency).

NAGS deficiency patients may have issues with the long arm of chromosome 17; clinically, they can be treated with carbarnemyl acid.

Ectopia lentis (dislocated lens).

Liver problems/cirrhosis, type 2 RTA, and a urine odor resembling cabbage.

Argininosuccinic aciduria (ASA).

Phenylketonuria (PKU) due to PAH deficiency.

CPS1 deficiency.

Elevated homocysteine, ectopia lentis, and intellectual disability/microcephaly.

Ornithine transcarbamylase (OTC) deficiency.

Elevated ammonia, elevated citrulline, and elevated argininosuccinate.

Argininemia (Arginase deficiency).

The ability to treat it with carbarnemyl acid, a structural analog of N-acetylglutamate.

Phenylketonuria (PKU) due to PAH deficiency.

CPS1 deficiency.

Elevated homocysteine, ectopia lentis, and intellectual disability/microcephaly.

Ornithine transcarbamylase (OTC) deficiency.

Elevated ammonia, elevated citrulline, and elevated argininosuccinate.

Argininemia (Arginase deficiency).

The ability to treat it with carbarnemyl acid, a structural analog of N-acetylglutamate.