¶ Lesch-Nyhan Syndrome: Case Presentation
All right. Welcome. My name is Divine. This is episode 648 of the Divine Intervention Podcast. And in today's podcast, we're going to be continuing the rapid review series for step two CK and step three. This is going to be series 135. Alright, so what if they give you a question? About a boy and they tell you that uh you know he's a seven year old boy and they tell you that. His dad uh brings him to the emergency room. Because for the last
Two days this boy has been having significant pain in his great toe, right? Significant right great toe, right sided grit toe pain, right? And then you're toting the question that uh this boy, uh that uh many maternal brothers uh have also had uh similar symptoms, you know, over the course of their life. And then they show you photos and you see these boys' fingers and these boys fingers just look very natural.
You know, you see all these like lesions on the fingers, right? Um you just see all these lesions on the the the the fingers just l look very nice. The fingers, the nails look very short, and all those things, right? And then they ask you which of the following is the most likely on the line mechanism behind this person's uh uh problem. Well, I'd really hope that you're thinking of Defect in hypoxanthane guanine phosphoribosal transferase. Hypoxanthane guanine phosphoribosal transferies. HGPR.
Your mind you're like, wait what? Yeah, so what do you think this person has? Well this person has Lishnayan syndrome, right? This person has Lishnayan syndrome.
¶ Lesch-Nyhan Syndrome: Genetics and Management
So let's kind of talk about this, right? The the the thing is they love to test this on the exams. This is not just some step one factoid that they test. No. This is something that they also love to test on step two, CK, and step three. Right. But basically the way it's gonna present is you're gonna basically see a young boy, right? You know, that has like you know self-mutilation behavior, right? And he can have signs and symptoms of gall.
Right. So the pathophase of this disorder, right, is basically uh defecting HGPRT. HGPRT, right? So hypoxanthine, uh, guanine uh phosphoribosal transferase. Hypoxanthine guanine phosphoribosal transfer. This enzyme is needed in the purine salvage pathway, right? So the thing is sometimes on your exam. Instead of putting Lish Nihan syndrome as the answer or putting hypoxwang thin hypoxanthin guanine phosphoribosal transfer is defect as the answer.
What they can do is they can just put purine salvage disorder or something along those lines, right? Or something along those lines. That's a very common pattern that the US MLEs use to create answers to questions. They'll take what you know and describe the characteristic of it, right? Instead of giving you a direct sounding answer, right? So that's that that that's what's going on here, right? So these people, because they have issues with HGPRT.
They're gonna make tons of Eric acid, right? They're gonna make tons and tons and tons of irric acid. And all that iric acid they're making is gonna cause them problems, right? So that's why this boy has great topic, right? And you may wonder, divine, why did you include the tidbit that many maternal brothers have had a similar problem?
Well the reasoning there is that it's an excellent recessive disorder. Leshnaihan syndrome is an excellent recessive disorder. Right? It's an excellent recessive disorder. Right? So again, you're gonna see it in men, in boys and things. that right uh the uh kind of a fun fact about this disease believe it or not it was discovered by a medical student we're like wait what yeah it was discovered uh by a medical student that went to the same med school as myself you know many decades ago uh
I think he discovered it together with his attendant, right? It tell tells you a lot about uh Hopkins as a medical school, right? If medical students are discovering genetic diseases. But that's a different story for another day, right? But uh basically, right, these people are gonna have hyper hyper uh urocemia, right? So that can cause them to have uh gal.
Right. So again, the classic presentation is going to be a boy, right, that has a lot of self-mutilating behavior. They're going to present you from a pediatric perspective. on your exams. You're gonna see self mutilating behavior, right? You're gonna see signs of hyper urecemia, right? You're gonna see many times uh because they may not give you many clues other than the photo, right? You see that man this person is kinda chewing up their chewing up their
their hands, uh train up their nails and their fingers, right? That's self-mutilating behavior, right? That that that should make you think about Leishine Han. syndrome, right? That should make you think of Lishnehan syndrome. Right. So again, when you lack this enzyme, you're gonna have too much uric acid, right? You're gonna have too much uric uric uric acid, right? Too much uric acid
So how do we treat these people? Well the thing is there's really not much you can use for the behavioral problems that they have. You know, sometimes you can give them like uh you know like medications that can help with anxiety, but honestly for the most part, the only thing you can do for these people is is allopyranol, right? Is allopurinol, right? At least to help them with the galp problem that they have, to help them with the galp problem that
¶ Lynch Syndrome: Diagnosis and Screening
That you have, right? But that's about as much as you can do for these folks. All right. So uh let's go ahead to another another thing, right? So, what if they give you a question? uh patient, right? So they tell you that this is a uh thirty three year old female and you know you're told that for the last uh you
Three months she has noticed that she has been having a very heavy periods, right? And that even outside of her normal times where she has periods, she has like vaginal spotting, right? And then they tell you that this person has Family history, you know, multiple family members. Uh, you know, multiple family members have had like uh you know colorectal cancer, like in their 40s or in their 30s, right? And then they'll ask you which of the following represents the most appropriate next best.
I really hope you're picking the answer that talks about an endometral biopsy, right? You're like, okay, divine, where are you going with this one? Well, so what does this person have? Well the thing is this person in this question uh has a link. This person has Lynch syndrome, right? Remember, another name for Lynch syndrome you may see on your exams is HMPCC, right? Hereditary non-polyposis colorectal cancer, right? So this person is having heavy menses and this person is having vaginal spot.
That makes us really concerned about endometrial cancer, right? Because remember H M P C C tends to be associated with uh certain uh classic uh malignancies, right? So people that have HMPCC they tend to have a lot of uh colorectal cancer, right? A lot of endometrial cancer, a lot of ovarian cancer, right? And you can also have like cancer of the stomach, right?
stomach uh stomach cancers right so just something you want to keep at the back of your mind for for your exams right so uh if you notice right like that's why many family members Again, have had uh colorectal cancer uh very early in life, right? Uh, in fact, these people, you know, sometimes they can actually make a screening guideline question.
from Lynch syndrome. Right. People that have uh Lynch syndrome uh they they need to start getting colonoscopies very early in life around age twenty, right? They should be getting colonoscopies uh usually every every one to two years, right? Usually every one to two. Right. So what's the pathophase behind the Lynch syndrome or H N P C C well the pathophysiology here is that you have an issue with mismatch repair, right? You have an issue with mismatch repair, right?
If you have issues with mismatch repair, then the problem that's gonna happen is that uh, you know, especially micro satellites, right? So what what are micro-satellites? Well, the thing is micro satellites are short repeating segments of DNA, right? Short repeating segments of DNA. Right. So those are regions of the genome that are susceptible to uh mismatch of nucleotide.
Right. So the thing is mismatch repair genes, they actually do a lot of major work in these regions of the genome, in these microsatellites. Right. But if you have mutations in the mismatch repair gene, Then these microsatellites will have persistent mutations, right? That's actually what leads to a phenomenon known as microsatellite instability.
It just means that wow, you have a higher risk of accumulating mutations within these microsatellites compared to a normal person, right? And what are some of these mismatch repair genes that are non-functional in people that have hemochromatosis? Well, think of your MLs and your MS. your MLs and your MSs, right? So things like MLH one or MSH two or MSH Six, right? Uh there's another gene called PMS2, right? Uh I like to remember that as like premenstrual syndrome type two or whatever.
But anyhow, right? So uh PMS two, right? So these are all mismatch repair genes. When any of those things are non then you're you're gonna get in trouble on your on your exams, right? You're gonna get in trouble on your exams, right? So again, don't forget these people they can get a lot of uh CEO cancers, right? So they can get a lot of colorectal cancers, a lot of endometrial cancers.
a lot of ovarian cancers, right? A lot of ovarian cancers. And don't forget the screening guide on about studying at age twenty. They're gonna need colonoscopies every one to two years, right? Every one to two Right. So again on your exams they can present this in many different ways, right? They can present this with uh they they can talk about this disease, right? Lynch syndrome. That's probably like the least likely way they will test the information because everyone Knows that already.
Right, the more likely way they're gonna test it is to ask about a surrogate, like hey, what kind of disease screening should be done in these people? Right, as I've said, you're gonna be doing colonoscopies every one to two years starting at age 20, right? Or they can give you the alternate name, right? H M P C C Hair Different Polyposis colorectal cancer.
Right. Or they can test the mechanism behind the disease, right? Uh mismatch repair problems, right? You know, you have mutations in your mismatch repair gene. Right. Or they can even test it as uh genetic instability, right? They can call it genetic instability or microsatellite instability. Microsatellite instability. Right? And remember, what's the mode of inheritance of this disorder?
Well the mode of inheritance of this disorder is going to be autosomodominant, right? It's going to be inherited in an autosomodominant file. Right. So again, make sure you can put all these things together. Make sure you can put all these things together. Right. And in fact, they can even ask you like a kind of a strange question here. They can actually ask you a kind of a strange question here. You know, uh a person that has uh Lynch syndrome, they can ask
Uh which of the following intervention w will most likely reduce this patient's risk of uh of uh developing uh you know disease in the future? Uh you wanna pick the answer that talks about giving aspirin, right? Remember aspirin is actually decent, not extremely good, but it's actually decent for reducing your incidence with colorectal cancer, right? With colorectal cancer.
¶ Octreotide: Diverse Clinical Applications
It's kind of helpful from that perspective, right? So it's something that's certainly keeping your back pocket for your for your exams. All right. Now, one other thing I think I want to address uh here, so this will be my third point here today, is uh uh What are the things we use octreotide for on the US M L exams? Like literally, what are the things we use octriotite for on the US MLE?
Well, the thing is remember Octriotite is a somadostating analogue, right? It's literally a somadostating analog. And one thing it does is that it decreases production of many different hormones, right? Many different hormones, right? So say for example, if a person has a vipoma, right?
tumor that's making visuactive intestinal peptide where they have um you know reduced gastric acid production, where they have watery diarrhea, they have hypokelemia and things like that. Um octriotide is actually a very, very good treatment for Right, or if they give you a question about a person, you know, that their face looks very different compared to like a few years ago, right? And they're having like
uh you know, signs of heart failure and things like that, you're like, Ooh, this sounds a lot like acromegaly, right? So you have a tumor that is making a ton of growth hormone, right? You can shut that process down by giving True type. I give an orc, true type.
Right, although remember for acromegaly, right, you can do many other things like you can give a dopamine agonist as well, right? You can give uh pegvisomant, pegvisomant is a growth hormone receptor antagonist, right? And typically the best way to treat acromegaly is to do uh Uh is to remove the pituitary adenoma to remove the pituitary adenoma. Right now, another thing that you may see octeriotype being used for in your exams is you can see it actually being used.
a person that has cars noid syndrome, right? Octrootide is actually very, very effective. for decreasing the production of serotonin, right? It can basically like shut down serotonin production at the at the source, right? And then another thing you may also see octriothyde useful in your exams is you can use it's you you can see it use
When a person has like Sovageovarices, right? It's a very good way to lower portal pressures fairly quickly, right? So we're gonna give those people a IV octryotite. IV octryotite. Very, very effective for reducing portal pressures. Very very rapidly on your on your exams, right? Uh that's something you wanna try to achieve if a person has a bleediness of a gel verices, right? So just make sure you know about octreotide, right? It's just one of those things that you know
¶ Beta-Thalassemia: Pathophysiology and Symptoms
It's gonna pop up on your exams in some way, shape, or form, right? If it does, you'd be grateful that you paid attention to this podcast and you knew that piece of information. All right. Now, what if they give you a question about a patient? And they tell you that this patient is a um they they tell you that this patient is a is a s you know seven-year-old boy and this seven-year-old boy you're told that he's from um he's from Spain and that you know
For the last few months, you know, he's been reporting this just vague abdominal pain, right? And they tell you that physical examination discloses heparosplenomegaly, right? And you notice that this boy's indirebilobin is elevated. And you notice that his red cell distribution width is elevated, right? And then they tell you that um six uh grams per deciliter. If you see this, what what should you be thinking about?
I'd really hope you're saying that divine uh seems like this person has some kind of uh thalassemia, right? This person has some kind of thalassemia. In this case, probably beta thalassemia. But be careful, I'm saying probably, probably, probably.
Right? Because I know some people once they see Mediterranean ancestry, you know, a person from Libya or a person from Spain or a person just from any, you know, Mediterranean uh nation like Greece, they think immediately like this has to be better thalassemia. No, no.
In fact, our friends at the MBMEs, right, they can make it an alpha thalassemia question. They can make it an alpha thalassemia question. So just be careful about that, right? Be careful about that, right? So what are the key facts of this case that tell us that, ooh, this is probably uh Uh phalacemia. uh question. Well first things first we see like the anemia, right? We see the anemia
And the the anemia w so we see the anemia and it's microcytic, right? And this is in a person that is from a Mediterranean uh nation, right? And they have heparosplenomegaly, right? You put all these things together, you really should be thinking about thalassemia, right? So what are the high yield things to know about thalassemia, especially better thalassemia? Well, the thing is again, we tend to find it in in Mediterranean and
families, right? And the thing is if you have beta thalassemia, you're basically not making adequate amounts of beta-globin, right? So if you're not making adequate amounts of beta globin, uh alpha globin has like no marriage marriage partner, right? So the thing that's gonna happen is that
those alpha globin chains are gonna start accumulating, accumulating, accumulating, and they can literally cause damage to the red blood cell membrane. They can literally cause damage to the red blood cell membrane, right? And this, all of this tends to happen in the... In the spleen, right? So actually don't forget that when people have um beta thalassemia, especially, right, it tends to cause an extravascular hemolysis. extravascular the hemolysis. The hemolysis happens within the
within the spleen, right? So that's something that's pretty high yield to know for your exams, right? So that may explain why they have an indirect hyperbillierbinemia. Because remember whenever you break down red blood cells, you're gonna develop you you're gonna generate indirect
bilirubin, right? Now let's look at some of the other findings here, right? So remember these people are also going to have microcytic anemia, right? And again, they have microcytic anemia because they are literally not able to make enough hemoglobin, right?
Whenever your body sees that it's struggling to make hemoglobin, it's going to try to shrink the size of the red blood cell, right? Because again, remember, what is the job of a red blood cell? Well, whenever you're you if you're a red blood cell,
When you get to the lungs, you're supposed to take up oxygen and dump off carbon dioxide, right? You're literally supposed to take up oxygen and dump off carbon dioxide, right? The thing is for oxygen to be For oxygen to literally come into the red blood cell. You're going to need uh help, right? You're gonna need help from concentration, right? You're gonna need help from concentration.
Right. So the thing is if your hemoglobin is so low, that may impair the concentration of hemoglobin in that red blood cell, right? So one of the ways to maintain that concentration so that gas exchange is still efficient and effective. is to make the red blood cells smaller, right? Shrink the size of the red blood cell.
¶ Beta-Thalassemia: Diagnosis and Treatment
That's literally the mechanism behind microcytosis in people that have microcytic anemia, right? Now what are some other things we see in beta thalassemia, right? Again. Uh typically these people are gonna have a microacidic anemia. You're gonna see target cells on a blood smear. You're gonna see target cells on a blood smear, right? And the theme is think about it, this is a globin problem.
This is a globin problem. So because we have too much globin, remember, um, heme is from from iron and protoporphyrin. Right? And then heme plus globin forms hemoglobin. Right? So the thing is if you cannot make globin, then you're gonna start having a build-up of heme, build up of him, build up of him. And as him starts building up, then you're going to start having a build up on.
iron and protoporin, right? In fact, one thing that's pretty high yield to know for your exams is that basal thalassemia is an iron overload state. Better thalassemia is an iron overload state. That's why sometimes these people that have thalassemia, right, you may notice that sometimes they actually end up requiring. Ah.
iron key liters, right? Sometimes they end up requiring iron iron key liters, right? Remember your key iron key liters gonna be things like deferroxamina or deferacerox, right? Uh that's how we also manage heritage for hemochromatosis, right? Where you have uh too much too much iron uh around
Right. Um so it's pretty high you to keep this at the back of your mind for your exams, right? And the thing is again, because people that have thalassemia, their red blood cells turn over very quickly, right? They're gonna keep making red cells, making red cells, making red cells, making red cells. Right. So the thing is because these people are constantly making a lot of new sales, they're gonna run out of their foliage very fast. Remember, we only have about uh
10 weeks worth of folate in the human body, right? So if you are constantly training and making cells, constantly training and making cells. The thing is, over time you're gonna run out of foliage, right? So, whenever people have chronic hemolysis from the disorder that they have, it is actually super high to know that those people should get.
Follate supplementation. They should get full late supplementation. They should get full aid supplementation. Right. And remember, you're gonna diagnose hemochromatosis. I mean sorry, not hemochromatosis, beta thalassemia by doing uh hemoglobin electrophoresis, right? So what are you gonna find on hemoglobin electrophoresis? Well, first things first you're gonna see decreased amounts of hemoglobin A. You're gonna see decreased amounts of hemoglobin A.
Uh well what's hemoglobin A? Hemoglobin A is regular adult hemoglobin, right? It's gonna be um alpha two, uh beta two, alpha two, beta two. Well, because you don't have enough beta globin chains around, uh you you're not gonna have uh And then another thing you're gonna find on hemoglobin electrophoresis is you're gonna see an increase in hemoglobin A2. Right? Hemoglobin A2 is alpha two delta two, alpha two delta two, alpha two, delta two, alpha two delta
Right. Notice this hemoglobin does not contain the beta-globin chain, right? So it's acceptable. And also, people that have thalassemia, they can also have an increase in hemoglobin F, right? That's alpha 2, gamma 2, alpha 2, gamma 2, alpha 2, gamma 2, right? So again, it's pretty high yield to know that for the purposes of your of your exam. Right. Because many people think that oh hemoglobin F is only increased in people that have sickle cell disease.
Right? Sickle cell disease is a better globin problem. But guess what, guys? Thalassemia is also a better globin problem. So why is it that sickle cell disease will be expected to have um An increase in hemoglobin F, and then magically that's not an issue with thalassemia. No, you do have this problem starting with uh with. You do have this problem certainly with thala thalassemia.
Right. And again, the thing is, you know, if they have severe thalassemia, you can do like blood transfusions, right? Again, don't forget the iron chylation. Uh, don't forget these people being on a folic, folic acid, right? People being on folic acid because again they can run out of their folate quick.
and develop a secondary or folate uh deficiency, right? A secondary folate folate deficiency, right? And again, don't forget, uh, you know, they they may have like a perosplenomegaly, right? Uh they can have uh uh iron overload and and things and things like like that, right? Uh you you're gonna see the target cells on a blood smear, right? And all
¶ Episode Conclusion and Resources
Fancy things. So again, I'd certainly know these for your for your exams, right? So I I think today my my main purpose with this podcast was to make a podcast.
That was a rapid review podcast, but it focused quite heavily on uh multi systems, uh processes and disorders. Right. Multi-systems processes and disorders. Right. If you notice I talked about like four cases today, but for each of those cases I went at depth, kinda talking through all the different things they can test you with on your exam.
And again, the reason I'm doing that is because, right, these things you you do need to know them in a sufficient amount of detail, right? You do need to know them in a sufficient amount of detail. In the future, God willing, I'm gonna make some more podcasts, right? I'm gonna make some more podcasts that address these kinds.
Right. So I think I'm gonna go ahead and stop here. Uh again, if you love the way I teach, you're gonna love my classes. Uh in the month of May, I have a series of classes for step one. Step two and step. Right? Step one, step two and step step three. Right. So if you're interested in any of those classes, Just shoot me an email and I will gladly give you some more information. I'd gladly give you some more information.
And then I also offer one on one children for all the USMLE and ComLEX exams and medical school exams and the EBIM internal medicine board exam. Actually I have an EBIM uh internal medicine board review course coming up on the month of uh July.
Right. And then uh so if you're interested in any of my classes, shoot me an email, I can give you some more information. I also have a podcast on my website where I kinda talk through all my different classes and what you should expect to get from from them. And then I have these podcasts on Apple, Google and Spotify. So check those out. I have a YouTube channel where I post the videos that I make. Check that out.
And then I have another uh website called divine intervention lifelessons.com. Divine intervention life lessons dot com. Uh many of you listening to this podcast now I'm a Christ follower, right? So uh every week I post like one or two podcasts where from a biblical perspective I address a life lesson. the life divine intervention lifelessons.com. There's almost 400 episodes on there. Many people listen to these podcasts. They find them to be very, very helpful. Very, very, very helpful. Right?
And um there's actually an Apple podcast associated with that called the Divine Intervention Life Lessons Podcast, right? And then finally, um I do help with ERA C applications, mock interviews, personal statements, uh rec letters and things. That. So if that's something you're interested in, again shoot me an email through the website and I can give you some more information. So uh thank you for listening to me today. I will see you, God willing, in episode six hundred and
uh forty nine I think. So have a wonderful day. Uh God bless you and uh bye for now. Thank you.