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doing? Thanks for the introduction. So in jail to show my screen. You see that? Yes, that So I I'm sorry you're on the 30 of Medical Student and today I was going to talking to you guys a little bit about metabolic medicine. So today I'm gonna be covering the familiar dyslipidemia as the lives in so much storage of soldiers and the glycogen storage disorders. So, in traditional pre pre easy Aussies e style and we start off with some SPF and then gonna get into the content. So a six year old boys brought to the emergency department after a traumatic for from his bicycle physical examination shows a large laceration of his left leg as irrigated in closing futures. Well, he's receiving care routine. Much draw shows milky plasma it forms a creamy appearing supinated upon standing for the testing shows that his plasma like bruising like pays activity measured after intravenous heparin administration is substantially lower than normal. If his condition remains untreated, this patient most likely develop which of the following teachers. Just a second. We're getting the bowling sorted. Okay? Yeah, yeah, I got it. So is it a a coupon? Cryptitis be intellectual disability. See my college and fortune de tendons and Irma's or example Hospice going to stop the ball around 60%. You're perfect. So yeah, the majority of you went a which is the correct answer. Changed that. So, yeah, A is the correct answer. And so, um, this patient is presenting with type one formula dyslipidemia otherwise known this familial hyper. Oh, um, call Micro Neemia. So and so the reason why it's acute pancreatitis is because type one familial on dyslipidemia is quite unique. And the fact that they don't increase the risk of myocardial infarction, unlike the other discipline lipidemia. And they actually don't commonly they can. They don't comment. He ever present with tendon. So in terms of those underclassmen and they don't handle effect until the course intellectual disability. So the correct answer would have been a And so just looking through the question my what would have made you on go for your your major diagnosis being type on the middle of this lipidemia. So what would have tips you towards that direction would have been the creamy appearing supinated. So therefore me milky plasma and the reason why I got this firmly milky plasma is because you get high levels of the triglyceride is in the blood Well, which is type one familial dyslipidemia. And what this does is it causes this firmly appearance. So that's one of you. The next clue you would have bean on the fact that went on this boy when he was administered heparin on He had a lower than normal life of protein like please. So in type one familiar dyslipidemia is basically you get a dysfunction in the life of protein like peas on enzyme. And so this enzyme, what it typically does in the body is it cleaves triglyceride and allows cells uptake. So when you wanna dysfunctions, you get high level two triglyceride in the blood and you get this for me and I'm super latent. And you also get Lew um, low levels of like putting like activity. And so what happened does is it Basically this enzyme, like a protein like pays, is attached on two cells using like heparin sulfite. So when you administer heparin, you basically disassociate this enzyme, and so you can measure it and in the blood until that's why then, that medicine heparin and so those are the tea. The two clues that would have led you to type one and giving you them legend to the common feature off type One communities, a bloody me, which is, and like you pancreatitis So on. Let's let's actually get talking about familiar difficulty years. So before we actually do that, actually, what? I was going to go through some of the signs hypolipidemia just to make sure. And you guys know what I'm talking about when I go onto the next light. So if you guys could pop it in the chart, what is the one on the furthest left? How would you describe that? Any score, Guess? Yep. Santyl as, um, perfect. And one in the middle. What is that? I guess One in the middle. Yep. Sounds perfect. And one in the fall, right. Cornea. August. Yep. This way, guys got 100 self correct. So Santyl asthma, tendinous, xanthomas and corn Yorkis. And so these findings only typically found em in patients with severely elevated lipids. And so they quite commonly present in familiar dyslipidemia is But don't present in, um more in conditions where you have a slightly elevated lipids in the blood So let's be about next line. So this is the table. So basically, initially I'm going to try to give you a framework. We're thinking about four million dyslipidemia is. So I'm not going to actually am asked you to memorize these people go through the state. But maybe I'm going to give you a far better way of learning and thinking about familiar dyslipidemia. Is that what you typically get? So this is a kind of typical table that you would see in in most of your textbooks, but we're not going to use that we're going to use. I'm going to give you one sentence, which I used to memorize all of my familiar dyslipidemia and they found a big puzzle, but it's actually really quite helpful, I find. So the phrase is one LP to L. D. Be on V three is 80 and forgets more. So if you guys want to go go along with me because once you really memorize this, like to be honest, it's an excellent framework, and it makes it a lot easier to memorize on. Do understand you're familiar with dyslipidemia. So it's one l p two l d. The odds V three is he and forgets more so what is actually need. So the one LP describes on type one familial dyslipidemia, so the familial hypo and call in Micronesia. So, as I mentioned earlier in the previous question and type one, you got disputation in the lipoprotein like paste. And so the LP in the in the center kind of stands for like a protein like beating. So you get this lipoprotein Life is on deficiency and the pee kind of starts of pancreatitis. So pancreatitis is the the high yield clinical finding you'll find in type one familiar dyslipidemia. And just as a general room, whenever you get severely elevated triglyceride, you will always get pancreatitis. It's just on. I'll talk about the mechanism in my up and coming slides. But if you just remember that, for now pancreatitis is caused by one of the causes is elevated triglyceride. That's how quite a nice way of thinking about Type one. And so, in Type one, you got this highly elevated triglyceride because lipoprotein I paid is used to break down triglyceride toe and use that and then up to is broken down by trying while I put in libraries know to be up taking into cells. Okay, so what is two out to L. D? So two l d basically refers to the second type of familial dyslipidemia otherwise known is familial hypercholesterolemia. What you guys might have heard of this is really common, and it's quite a common cause off early onset acute coronary syndrome. And so the L D basically represents algae, all receptor deficiency. So in familial hypercholesterolemia, you get mutations in this LDL receptor until you can't take out deal from the blood so the liver can take a can't optic LDL and LDL is kind of is the main driving factor in after school roses on so you. That's why it's quite a because of increased risk of acute coronary syndrome. And you also get this tendons anthem is us the key high your clinical finding you tend to find in patients with familial hypercholesterolemia and the tent okay on the Achilles tendon. So if that's a that's what the two of the two l D means. And if you guys mentioned noticed earlier, I'll just go back just so you guys can see they're two types off, um, two subtypes of type two familiar dyslipidemia is this Type A in this type B and so a good way of thinking about this is good is be odd. V So B is the type is type two b. You have time to being in touch. A. So in type two B, you basically have everything that you have. In fact, they they basically also get very lewd and street like routines you get also your sugar elevated know density lipoprotein. So it's everything. And then you get in and familial hypercholesterolemia where you also get elevated on very allude entity lipoproteins and the three e So in type three formula dyslipidemia, you get a deficiency in April. So April is basically what's used to update call a micron remnants, remnants and very little video audio, but very low density lipoprotein remnants from the blood. And so, if you have this deficiency, you gotta build up of these remnants in the blood. And so you get this hyperlipidemia. And so a common key clinical finding is good. Palmer's anthem, And so you get these fatty deposits around the hands and the way I think of it is I think of three. So I think the hand, and I think about these Palmer's on Coumadin. And so that's for Type three ability Dyslipidemia as and then four gets more and so in type for some people like to think of it as VLDL has four letters indeed the LDL. So therefore, four and some people I think I get more, gets over production off the LDL and so on in type four again, this overproduction be it'd be LDL VLDL predominately contained triglyceride issue get elevated, triglyceride is in the blood. And when your elevate trigger slides and blood your pancreatitis And so that's basically just a nice framework for you guys to think off and to memorize that, um, the familial dyslipidemia. So if you just remember this line on one LP to L. D. B adds be three is e and forgets more. You can use that whenever you see a question of familiar distributing. So as I mentioned earlier and you get pancreatitis when you have elevated triglyceride and so the mechanism isn't 100% understood. But, um, one of the theories is the increased call in microns cause the increase in triglyceride. So I'm actually sorry what I meant to say was when you got in. When you have high amount of triglyceride after meals, you always get increased calling my crowns and these increased levels of triglyceride. What they do is they cause obstruction of the capillaries because the skinnier and this is Humira basically causes a breakdown off cells and that they released this pancreatic light pieces and the pancreatic like bees breakdown priest, three fatty acids and the free fatty acids causing immune response, which causes pancreatitis. And so that's one of the theories for why, when you have high levels of triglyceride and get acute pancreatitis, so it's a bit more detail from that framework on the formula is nobody knows I'm just going through each of them. So in type One you get these week. Recurrent pancreatitis on the treatment is usually very low fat diet, very low fat diet. And they have been reported people having normal life expectancies with type one and so one of the key clinical features is severely ever elevated, triglyceride and severely elevated on calling my crowns. And it's also auto order, some more recessive, similar liter, most of the other from a little dyslipidemia. So Type two is very unique in the fact that it's autosomal dominant. And so, um, one of the key things to know about familiar or hyper familial type two on dyslipidemia, or familial hypercholesterolemia is patient to a homozygous, so they have to a wheels that cause a defect in the LDL receptors. They tend to have far worse prognosis than patients who are heterozygous, so they have only warn on a little of that, effective all the old receptive. So patients who are homozygous they tend a very, very few LDL receptors, or heterozygous. Patients have a bit more receptors, and so they tend to do on better than on homozygous counterparts. And so the's patients who are home is, I guess these are the ones who tend to have my records. Unfortunately, the very early twenties and the and patients who have generally have familial hypercholesterolemia can present with these findings of off a xanthelasma something water and corn Yorkers. So then you have type three familiar, this beta little lipoprotein EMEA stupid about school of a mouthful, but aside mentioned earlier, it's a defect. In this April, we, um, subtype, And so when you have this defect, you can't update these called micro calling micron remnants and be LDL. And so you got elevated total cholesterol and trying to write. And this one also does increase causes, increase the rate of acute coronary syndrome and cause the premature coronary disease. And the fourth type is hyper Try righty me in, and it's also song dominant, and you get this over production of the LDL, and so you're over production or you can get impacted. Top of them tumbled is, um, all the LDL, depending on the type of it's further, some type of tight fall, and I try, um, let's ride demon. And so, um, this condition is quite often associate with type two diabetes, and it's often diagnosed on routine blood screening, and these patients also have an increased risk of coronary artery disease. So basically, if you remember that type two is the only type one sorry is the only one that you don't get an increased risk of coronary artery disease. You can basically remember that all the rest of them you're the increased risk of coronary disease. Yes, of the next Spn, the patient, the parents of a two year old girl bring their daughter to the office for a routine checkup. They have noticed that the child's abdomen appears swollen, but she has had been otherwise healthy. Physical examination shows, hepatomegaly and mildly decreased muscle tone by a chemical called testing shows. No fasting blood glucose elevated triglyceride elevated, creating kind is and normal acting levels. Additional evaluation reveals my mild hypertrophic cardiomyopathy. This child's findings would be best explained by defect in which is the following cleavage off the Alpha one for Glaxo bonds. Off blockage and Lies is, um's, um, and you wanted to before so the majority stopped wearing the polls. So the majority of you guys went for see, um, how with correct answer is d treat this one. So the correct answer was actually D, and I kind of think in a way, you guys kind of went wrong. So I think a lot of you guys thought this was born because disease on, however, it's actually Corey's and disease. Well, bongo cause does present very similarly to Corey's disease, but the key difference is the fact that Invokana, which is a type one blockage in storage disorder, you don't you don't get any effect on muscle tone. The muscles are completely unaffected in type one of in type three, you do get some effect on muscle on the musculature and Corey's disease. Everything is Basically, you can think, of course, is is basically a a toned down version of ongoing So and bongo you would get extremely low on fasting, blood glucose when choruses these you get, um, only low and in in Vongo cause you get I'm quite extensive hypertrophic cardiomyopathy. But in chorus disease, you know, get mild. I'm happy to record it myopathy, and to um that would have put it towards direction. Of course, is is, and you think, What is the mutation in chorus disease that causes the disease on? But it's a mutation in the alpha one black stick bond off blockage in yeah, and the removal in the roof of the of the linkage lyrical. Second, his enzyme that removes this group of seconds. That's a nice question. So let's go through the glycogen storage disorder, so I'm a good way of remembering. The name is very poor carbohydrate metabolism that there's more than these on for. For these of the common types on this is at least 15 is very many but on good remembering is very poor carbohydrate metabolism, so you have type one bond. Okay, type two pump a disease type three Corrie disease and type four type 35 called seas. And so the periodic acid sustained identifies glycogen and is useful in diagnosing these conditions. So let's have a look at which enzymes actually affected them. So a Z I mentioned earlier. So for for Korea's disease, you get this mutation in this deep bronchial time, which targets that was awful. 16 like acidic bombs. Well, it's formed. Go, go! You only get on your mutation in the glucose six phosphate. And so the reason why I am in chorus disease you got this effect on musculature is because glucose six phosphate is an enzyme that is only found in liver. And so because the mutation isn't founded and muscles you don't get on defect off, you don't get the decrease muscle tone, and they usually get in chorus disease, which effects this, which affects the D branching enzyme in in the glycogen breakdown pathway which is found in muscles. And so um, and awful 16 glucoside days is Pompeii's disease and more call disease is classic phosphorylase. So let's go into a bit more detail about these collected instructions. Uses So bonkers disease type one is a It's a mutation because on 5 ft and so part of the reason, if we just go back. So it's easy to explain on the cascade. Part of the reason why it causes is very, very low levels of glucose is because glucose 643 is a key enzyme in gluconeogenesis. So without Lupus, with six phosphate, you can't convert. You convert. For instance, fats seems triglyceride into glucose, so the components off the triglyceride component, which converted into glucose, is the glycerol. Remember that you can't convert fatty acids into glucose, but the cholesterol component could be converted into glucose so you can't do that. And so that was part of the reason why you get this very, very low and fasting. Glucose is if of the Beijing hasn't had a meal for a while, and you could also can break down like a gym to make it into glucose and for the blood, basically. So when glucose is in, it's click or six phosphates, Um, state. It can't lead cells because the phosphate is charged. And so you can't go past fossil little remembering. So you need to dephosphorylation in order for it to be in the bloodstream. And so when you have mutations that enzyme, you're very little blood glucose levels. That's kind of the key part of physiology of on Lyrica is disease. So, as as it's written here, is characterized by severe fasting hyperglycemia. Good, because you can break down the glycogen. You get increased, like in stores and liver and kidneys, and you also get an increase in blood. Lacked it. And so, in the chorus cycle, you got conversion off laxative into glucose. But if you can't and convert it, because if you don't have an effective if you don't have a function of nickels five phosphate enzyme possiblity Sorry, that's extruded. Criticize faucet, ease enzyme You can't convert on the lactate in the glucose is you're gonna build up off lactate in the bloodstream. She gets elevated, but a lot of like late similarly, because you can't break down that glycerol component off triglyceride, since without the Group of Five possibilities, you ever elevated triglyceride and you also get increase in, um, your uric acid and that part of my golly is caused by the built off blockaging in the deliver. Similarly with the renal, maybe until further notes, it's usually treated. So you you presented infants. So, um so really, you're getting a lot of people's lives. And so the treatment is typically frequent or a blue coast and cornstarch. And they have to avoid fructose collectors on these sugars because the sugar is also quite because six force because 54 speed. Sorry on because five possibilities to metabolize So pump a disease type two. So, um, and this one, you got a mutation in that, um, in this enzyme so awful one glucoside days, which is forming lies, assumes. And so what happens is you get a build up off your ability of blockage and analyze is, um's. And so you tend to get, um, again you get build up off glycogen in the heart because you can't properly metabolize it. So you get called your regular. You tend to get happy to have a cardiomyopathy. You tend to get hypotonia because that enzyme, the sense I'm off nice is, um, well, acid. One offer one focus I days is found in is found in muscle cells. So you tend to get this hypotonia your exercise intolerance. And when you refined the stomach findings, this is quite leave. It also tends to on me to death. So a good way of remembering this, um, this building off one part of the political master tonic manifestations upon pays disease is Pompeii. Trash is the part. So that's just a nice little ky and clinical feature to find after a member for Pompey Disease. Sorry. So it's glucose five foster teas. Yes. Good, good. Five. Positive. I'm sorry. I think that Zicam pleat type of my apologies it's glucose six phosphatase. Yeah, just completely ignore that. It's like a six foster days because it the phosphate is found on the sixth carbonyl the glucose, the nickel. Six months of these for bond get occurs. I understand. So Cory is disease, So cars disease is you had a mutation in the deep bronchial times, so yet you're awful once a week ascites and affected. It doesn't work and you can't. Your muscles can't utilize our blankets and effectively. And so you returned to get milder symptoms than one ghirga. But you also get this colleague mail procedure to the bill of blockage in themselves. But you do get normal blood black the levels because you can still convert lactate into glucose because I said separate pathway from the pathway. Get this Steven tree inside. So keynote is Google. Genesis isn't talked, and you can think, of course, is basically a tone down version of one. Okay, and my colleges disease. So because disease is effective, the so it's a mutation in the key and step in a blanket and break down like in phosphorylase. And so without it you can't break down the glycogen in skeletal muscle. And so these patients, they tend to get this second wind phenomenon. So when they're exercising, since initially the majority of your energy comes from Lucas, and then it moves on to glycogen for your muscles, and then it moves on the facts when you're trying to exercise. So since these patients they can begin the exercise, since they use their on their just the blood glucose initially and then once the they move on in and, as usual, is a shin, and they try to use Lukas, they tend to get these cramps because they can't break down, tickles and so they also tend to get this increase in creating kinds levels as well. Because you get damaged too, and the muscles because of the Indian ability to utilize glucose, then after a while, so it takes time for lipid metabolism to increase. You get the second one phenomenon where they're able to utilize their lipids. Nordic energy. Uh, so that's a key clinical finding. And McCall's disease. Yeah, so they get the tendon and he's paying for muscle crimes initially and myoglobinuria to get red urine, and they also have this. They find exercise quite strenuous, and they can also get arrhythmias from our electrolytes. Electrolytes and balance is is well, so next best be a A physician is seeing a 17 year old girl for the first time for her sports physical. She says she has not been involved in organized sports before, but is thinking of going off a cross country this year just to get in better shape before going away to college next year. Just notice leg cramps and weakness. After starting to run, the symptoms improve that she continues to run. You also states that sometimes after a run, your intense pinkish red for a while the physician suspects a type one or a type of black shin story disease. Um, three position suspects a type of glaucoma storage disease could explain the gills symptoms. Which of the following findings would best confirm the physician suspicion So perfect. So the majority of you guys have chosen See, um, which, unfortunately, isn't the correct answers. And the correct answer is a, um, as in type four. So this is my calls disease, because you tend, you see this, um so the pinkish red your insulin. So as I mentioned earlier, and clinical findings two years myoglobinuria good the second wind phenomenon, um, in Michael's disease. So so that would have tipped to do towards the diagnosis being more colleges, disease. And then in Michael's disease, you tend to get this increase in serum correction in addressed because of the inability Teo utilize glycogen. Until that would be, the findings of the diagnosis would be my calls disease. On the clinical findings to be elevated serum crashing kind is I love to see them crashing kind of level at rest. So next day. So a fun one year old boy, I hope that make sense. Guys if you guys have any questions, feel free to problem. No. A four month year old boy is brought to the emergency department 15 minutes after having a seizure. His parents of four days being very fussy at night, unable to wean off night time feedings. Physical examination shows a tie child with don't like feces with fat cheeks, thin lace, short stature, perturbation abdomen with enlarged liver. There no neurological. The effects. Initial testing was a plasma sample low glucose elevated lactate elevated uric acid and elevates triglyceride. Biochemical testing is most like 10 streets that a deficiency in which of the following enzymes. Uh, actually, my apologies, guys, I think been a rough that question that the enzymes on there so actually ignore that question for now. Sorry, the enzymes aren't there. So for this question is, should have been a typical sort of typical presentation to a four year old boy. This would have been Corey's disease on again because, you know, on glucose elevated triglyceride. So that was my my apologies of mistakes. And if you ever see this, just think of the typical presentation off of a patient with Corey's disease. So and then the the deficiency in the enzymes would have bean. Yes, it would be in. Listen, it would have been in the awful one with the ascites the Debrox checking on the debunking enzymes. So the this this one is correct. True. So a six year old month year old boy presents the generics clinic with a one month history of swallowing movement difficulties. A genetic test is done for red. Is is which demonstrates a four piece Paris insertional creams and 15 causing defects in the enzyme. Excellent. And I mean, how many days a what I would have gene mutation. Is this again? My apologies for the previous question have against the majority of guys. Got to write them. Crack town is a frame shifts. Yeah. So this is a classic presentation of allies. Is normal storage, disease and lives, um, in storage disorders. Um, which will go into after you guys will take a three minute break and then we'll go into this is normal stories, just holders. So if we come back at approximately 7. 45 then I'll go through the lives almost always your shoulders. Think you sound great presentation so far. Thank you. I've put link in the chapped for the preteen easy main list. If anybody wants to join that, you just received updates about our latest lectures that coming up Onda, obviously check Facebook for a while. The events coming up as well. Yeah, because where you stop So I'm modified of corrected the question Those those error in on. I've also modified a slightly. So, um, if you guys want to try this question, um, all waiting for it will come back. I made a area. So this is this is not typical presentation of Corey's disease. Sorry. That's not It's not. It's I, I would say, actually, no way for us. Sounds delicious. Yeah. Perfect. So that the majority of you went for a which would have been correct. But this is not Corey's on. Does not approve a presentation of Korea's disease due to the elevated A Lactaid. So this is the what? This is a disease. It's very similar. Score is disease. This is, um this is one. This is one good one Gogurt disease. So and do to the elevated like that. You don't get elevated like that. You can normal lactate in chorus ease, so let me just quickly go through the difference again just to clarify. So in Corey's disease and you have normal blood lactate levels, you effectively get similar on your milder symptoms and then bang ago. But a key difference. You had two French eating factor between Corey's disease on one a day. Okay, is Mongolia and you have elevated blood lactic levels? Yeah, so elevated prolactin. It just typical finding elevated your glycogen and liver and kidneys. So you get a part to and read. Um, actually, is some of the findings you find in both diseases, but they just milder and Corey's disease hope that's clarified things. If you guys have any questions at all, just problem in the chart. So let's go into, like, zoom well storage soldiers before we do that. Can you? Can someone tell me which lies is almost always? Disorder is found in this question. It's public job, I guess so. Okay, I was going to get it's taste socks. It's quite a it's taste access characterized, but the mutation on mutational comes and 15 please. So let's go into my eyes. Normal storage of soldiers so But before we do, that was quickly run through Onglyza seems that functions to realize, um so just remembering Bound organize found with themselves the content enzymes to break down numerous biological substances proteins you play gas is carbohydrates and lipids on day also digest One of the main functions is the kind of clean up the cell, so they don't they don't they digest obsolete components of cells. So, um, what character? What is typical of allies normal storage disorders is they usually have a inability to break down specific molecules and they cause the accumulation. And so most of them order some more excessive, and most of them have no treatment or cure. So so, typically and all the lies and story short, I'm going to talk about basically derived from shingles lipids. So if you guys can see my mouth's, I was going to effectively So single scene Is it very similar to fatty acids, however, has to alcohol groups and also has on, um, you know, group is well, so as whereas a fatty acid would have a corpuscle agree with the and single you seen or single lipids in general on day have, um, alcohol and the media and we want you and So what happens? And to make them from single seen two single lipids on they get addition off this time a fatty acid chain and eso ceremony. It is a type of sugar lipid, so they that's that's what differentiates your single scene. Single lipids and most of the bladder of the eyes in storage disorders effective have difficulty breaking down on DPA doctors that are derived from these two components. So so some of them derivatives answer my derivatives. And so typically, um, what happens is the derivatives have used to remind base, and then the attach ahead group on to it. So some of these if you ride absolutely glycoprotein the glycogen, carbohydrates and sulfa component compounds on you get the formation of black of shingle lipids. So for tides and others, and these structures tend to be very important for nerve tissue. And so that's why you'll see that a lot of my normal stories disorders they tend to cause neurological problems on be due to the they don't just cause neurological problems as quite significant wants to. There's these conditions tend to present quite early and the development of Children. So I was going to talk about fibroids disease. So the bike the the the shingle of it that is not effectively broken down in families. Disease is, um, is effective. Is serum a died trihexyphenidyl It's got. It's quite a mouthful, and this is broken down by half a block to today's A and so in in families disease, which is, I think, is the most common type of lies own storage disorder. You get a deficiency in Africa Lactis side eight and you had accumulation, a sort of my trihexyphenidyl. And so and this disease is excellent process of which is unusual because, as most of the other labs normal, sorry like it's almost or disease. Order some more assessment, so you tend to get slow progression of symptoms new to begin in childhood and then develop on, too. Really, they continue on until early adult hood. And this is quite also is unusual because most of the other lives is almost always. Diseases are quite fatal until not bottom on gotchas disease, which is also you can get. Patients there live into early alcohol's into early adult hood on, but most of the other ones tend. It's very unusual is most patients on die in early development. And so one of the classical findings as us with most lives, is normal storage disorders and good neuropathy. He's your classically. You get pain in the limbs and hands and the feet you get on these Andrew current term, as which I see image of the one there of some that on. But there was time to be quite benign, and you also get, um, you don't get dilated capillaries and you'll be These patients tend to sweat less. You get decreased sweating problems. Disease, some of the more sinister on manifestations of herpes disease, can cause neuropathies. They can cause renal failure and heart failure. They can also tend to cause transit. Seems tax and strokes and however, one of the treatments. And this is one of the diseases that does have a treatment, and you can basically effectively replace the enzymes deficient to help them break the galactic, Sam said. I've the black do. Today's didn't give them, not not black Mercedes. Think you can break down the the serum? Try exercise so using and we're confident Black Mercedes, which is enzyme. So just the key classic presentation is just really drill. It in. So I remember family's disease child with pain in the hands and feet, lack of sweat and skin findings. So the key mutation is a deficiency in our field. Electricity is a an accumulation of try and try a might try exercise, and this is empty. Another. Um, Mitchell, the in June I do and you and carry tumors You can find about this disease. So I'm moving onto couches disease, which is I always like to think of Goucher's and popular these together because these are the what conditions that most patients conserve. I've gone to adult early adult hood, so part of the difficulty of life, simple story diseases, it's kind of just memorizing the bizarre and substrates that aren't broken down. So, um, in in and got his disease on you can't basically breakdown. Click Oh, cerebral oh cerebroside on which are broken down by calico cerebroside days on group glucocerebroside eases. And so because you have a deficiency in the enzyme, which basically prevents its breakdown and a similar story, but the other lives almost or disease, you get accumulation off this byproduct and then you tend to get neurological disorders. So so the lipids These lipids can accumulate in spleen or liver bones, causing a part of splenomegaly and sperm megaly. Since this tends to present quite early in childhood, and since Children tend to be quite small, suspending megaly tends to be the most common. Initial finding on dissent also affect bones being caused thrombocytopenia the most cause rarely and neutropenia. And these patients do to the stronger cytopenia they present with on bruising very neatly easy, bruised. And they can also have a vascular necrosis with the Jones. And so the reason why they have this is in gouges disease on Do you effectively get the's got Your cells, which are basically macrophage is which have filled up with a lot of, um, lipid in the light is, um's, which hasn't been broken down properly. And so what these do is they effectively on the the the buildup in the medullary space, and they can basically cause a skinny and get this even, um, even in the crisis off the off the joint specialist on be the cause of neurological disorders so they can lead to this disease, complete to dementia, ataxia and gaze palsy as well on this one's them, like most of them is. Order some more resources. And so, as I was mentioning earlier on, I'm only gonna get a vascular necrosis. You can also get bone crisis. Caesar's in Got is disease. He get infarction off the bone on due to these got ourselves, which basically is Bakri. Just lift filled with eyes is, um's in the intramedullary space, and it causes intense pain, often associate it out. I'm often with fever, and it's very similar. Present very similarly to sickle cell disease. On a type one is it was common form of present assignment in early present. Some childhood, uh, other hood. These patients. They can have a normal lifespan for the other two and types on do death and entity is quite common, and Osama generally tends, have early childhood onset. So just the classic case, just the key findings of got his disease so thistime to be common in people and and asking people have asking as the Jewish descent. So people from activity Europe, Italy, on Germany, that region, the world, and Splenomegaly on examination is endorsing presented anemia and bruising Because of that from beside a pina and joint and pain fractions practice also very common. The key finding deficiency in glucose cerebral days. Definitively grocery work. Today's sorry, it's been a mouthful, an accumulation of glucose. So cerebroside, which is the, um substrate, which is so Sugar milon on. So, she reminded, is effectively the substrate that isn't broken down in and you and pick disease on. So you got this deficiency in sync a Mile and A Z um, accumulation. Single minded needs, which causes the disease so again it's autosomal recessive is common in asking is the Jewish population you tend to get splenomegaly, a neurological defects on there. Also, multiple subtypes of this disease, this one and it this one is far more lethal than the other two's of it it doesn't tend to. You don't tend to get a lot of patients making it too early, Adult hood. So you get these firm cells, which are effectively large macrophages filled with lipids, which are different to the garter cells. You get encounters disease on microscopy that until they look very, very different, you want to get on the accumulation off of these for themselves in the spleen and in bone marrow. And this this disease tends to cause quite severe in the severe form. Sindical is death and and in 3 to 4 years of the most patients die before they reached 84. So and one of the key findings is I'm sorry you got this progressive neuro impairment in new and pick disease. And so just in general, we'll talk about one of the key clinical findings you get in you and pick disease. But you also get in taste accidents. And so if you saw a patient like this and they were in that they were adult on, but your first clinical diagnosis would be a stroke. So a cent occlusion of the central retinal and artery so effectively you get this on paler region, so under by a darker red spot and so you wouldn't think of human pick out a socks bother. And with patients in childhood and early infancy, you're more but your top differential with those type of patients have been human pick and T and T socks. So and, um so the key findings in new and pick disease so previously a healthy child and then the 10 to get they tend the tend to lose their motor skills. So skills that they would have the had developed. On the 10th, they started losing the news and get this weakness in the news. The motor skills and you tend to see a large live in speed on physical examination. And again you get this cherry red spot. That's a classical cases. Key findings, deficiency and changing my late knees accumulation in general. My lung. So glad this river and collector cerebroside and the major component in mind so well. Actor cerebral side is broken down by Galactus Rebeuh. So days, which is when you get this, a deficiency in it, you get troubles. Cut crumbles, crumples disease. Sorry, um, so do so that accumulation off lactose free boost and said, I causes on GABA maladies you finding disease. So a similar story to the other allies of storage disease is so you tend to, um, usually presents and within six months of life on you tend to only get on your symptoms, and you tend to get this progressive weakness and the patients on get the developmental delay it can present with vision loss on beaver, often without affection, they usually causes death within the first two years of life So one of the key is logical. Findings of this disease is you get this global cell, the leukodystrophy. So you get the global cells in the urinal tissue. Yeah, to get 10 against more, get these multiple nuclei when you look at it under a microscope, So taste socks, disease. So, um, so taste socks Disease is a due to accumulation off at these GI ganglia sides. And so I always found that the's this notation was always looked very confusing was actually quite simple. So GI basically just refers to the fact that it is a It's a ganglioside mm. Refers to the number off the nana component. So Nana is effectively this your If I they see on, um, the M basically refers to the number. So if you had to, it would be diabetes. One b don't tend to get that. So it's GHI is for a scandal aside and refers to one of these non a legal legal saccharide. And 12 and three basically, um, refers to the positioning of these sugars. You have glucose collectors and another sugar. But on the order basically determines on the number ring that that the ganglioside gets And so it's accumulation of these gun MRI asides that causes taste oxygen. Then again, two socks disease conclusively present with just cherry red spot and also presents in the askin Ozzy Jewish population. And this is the deficiency and in excellent, um, are many days a keep. Keep that point. So most common form presents between three and six months of age. And get this progressive neurological tract urination. Get this exaggerated startle a reaction, which is a high yield clinical finding. It tends to progress its users and visual loss, and you also get paralysis. Intend to get death in the early childhood? Key finding is a key finding on histology has got these lies is, um's of the onion skin. So if you look at, if you actually have this like zones with multiple layers going around it and that is quite a classic finding and T sucks, doesn't it again order some more excessive? And one of the key since taste socks and crabs do, you can present very similarly one of the key things you can use. Different She The two is, um, trouble crabs. Disease presents in less in this first expensive life, where as Mt socks, diseased and most commonly presented with in with patients who are on two years with two years of age with Again T socks, you tend to get this do tentative gait problems, falls, hypotonia, speech problems and dementia and also, um, developed on most shoulder. And so, um, the finalize own storage disorder that I'm really talk about today is called metachromatic Leukodystrophy, so it's autosomal recessive. You get accumulation off Collector's riverside plus suffer acid is get is a major component of island. So basically, whenever the major component mile and you tend to get a lot of your old school disease. So these patients, they can actually also develop dementia. They tend to present hypotonia. They have speech problems, GI problems and name the commonly don't survive early childhood. And so, just to summarize, I'm skin Teo give you this because I know that was quite a lot of information, just going to give you a nice framework to think about all of these as normal storage disorders. So whenever you find a patient, you onda is effectively is older than really childhood. You you want to be thinking mawr off the fibroids and Galaxies disease. So if they have hand and feet pain and they have decreased sweating and rush, think fiber ease that speed anemia and fractures and dashes on. However, if they're big younger and they present with weakness, so that's a key difference between five rays and cultures. These ones, the patients tend to live a bit longer, and they don't have this neurological weakness. So if they presented with weakness and approximately two years old, you want to be thinking about metachromatic leukodystrophy. If they're older, slightly older child and you see this, you see liver and spend a Magalie and a cherry red spot. You want to be thinking about human pick if you if they're the baby and you don't see this on your cherry spot, but you still see this neurological disorders of weakness. You wanna be thinking crab crab's is disease? Apologies. If I'm not pronouncing the name of that disease correctly and if they're again, is on their their baby, and they are from the asking as a Jewish population with no splenomegaly and again the the cherry red spot, you want to be thinking about tea socks. So basically, if you remember this, this'll key and and divert here, you're basically you'll be able to diagnose your life simple story disorders. And just remember that all of the components that accumulated are derived from shingles, shingles, sign fatty acids and surrounded lines. That's just sometimes like to ask that one example. Thank you very much for listening on dollies philosophy bathroom. Before I finished, you guys have any questions at all spotting in the chart.