 Welcome back to our MedSmarter question of the week where we're taking a smarter approach to preparing future physicians. Before we get started, if you'll take just a quick minute and click that like button and also subscribe and turn the bell on so that you'll be notified when we post new videos. Let's get right to that question. As always, we start with the last sentence of the vignette and then go back and read the rest of the vignette. Which of the following is the cause of this patient's condition? A 40 year old woman presents to a new physician because of the recent onset of fatigue, arthralgias, discomfort in her right upper quadrant, and polyurea. On physical examination, her skin seems somewhat browner than would be expected. Lab tests are remarkable for an elevated glucose level, indications of homolysis, and increased transference saturation. Cardiac testing shows moderate restrictive cardiomyopathy. She mentions that she regularly requires blood transfusions, which the following is the cause of this patient's condition. So right from the bat, I saw a 40 year old female that had some right upper quadrant pain, I'm thinking possibly gallbladder issues, the fat fertile female 40. But when you went on further into that question, it obviously pointed us away from that. So we're talking about brown skin, we're talking about elevated glucose levels, homolysis, getting blood transfusions. So we're looking more into an issue with blood and that type of thing. So let's look, take a look at these answer choices, read the question again, come up with an answer and write it in the comment box below. Alright, so let's just go through these answer choices and see which ones would fit our clinical vignette and which ones would not. And then we can rule out some and maybe come with a better option for us. So A, mutations resulting in copper accumulation. We know that copper accumulation can cause some browning of the skin, this is called Wilson's disease. But we do also note that they typically will have Kaiser Fleischer rings. It will be a golden brown ring that you can see around the iris in the eye. There's no mention of that in this particular vignette. Some other symptoms associated with Wilson's disease, Parkinson's symptoms, asteroxys and dementia, not seeing any type of a mental deficiency in this patient. So I'm not really seeing clinical indications in this vignette that would lead me to believe that Wilson's disease was the issue. So I'm going to say no to A. B, absence of the hemoglobin alpha chain. So that is going to be an alpha thalassemia. If you're having a full absence of the alpha thalassemia, we're talking about a severe form of alpha thalassemia. Not having an alpha chain in your blood would be what is known as hemoglobin barts or HB barts. That's going to have major issues that aren't going to allow you to get to the 40 years age range before this type of thing comes along. So this is oftentimes intrauterine fetal death here with patients at HB barts. So therefore absence of the alpha chain is not an option for me either. Mutation in the hemoglobin beta chain. So that is a beta thalassemia. And if it's a mutation in the beta chain, it could be beta thalassemia minor or major. We are seeing homolysis and ineffective erythropoiesis in this patient. So I'm thinking that C could be a possible answer. Let's continue on and look at some more options here. Mutation resulting in increased absorption of dietary iron. So we do see some cardiac abnormalities here where we have that restrictive cardiomyopathy. That can be something that is seen in an issue with iron. But it appears that in this particular case, the patient's restrictive cardiomyopathy is likely more because of those regular blood transfusions rather than because of something like hereditary hemochromatosis, which is what we're seeing described in option D. So to me, D is not a possible answer choice here either. And then finally in option E, mutations in the gene encoding anchoring. If you can remember about anchoring, anchoring is something that's associated with a mutation for hereditary spherocytosis. So that is what is associated with the cytoskeleton of erythrocytes. With a mutation in anchoring, then the erythrocytes no longer take that bicon cave shape, but they become more of a sphere where we get the spherocytosis from. We do see some homolysis with this, so that does show some indications of homolysis that we do see in the vignette. However, this is not something that would match up here because we would see gallstones, anemia, jaundice, splenomegaly. None of those are we seeing in this vignette. So therefore, I am ruling out E is a possible answer choice, which leaves me only with one choice C, a mutation in the hemoglobin beta chain. And C is the correct answer. So like we said, this is a beta thalassemia. So we're seeing severe homolysis, which is what we can see here, this indication of homolysis. And then when we're seeing that she already gets regular blood transfusions, that's because with a beta thalassemia, they need normal blood often to replace those blood cells. So what we do end up seeing is an iron overload. So that iron overload from multiple blood transfusions is where we have what is known as transfusion dependency or secondary hemochromatosis, which is what's being described here. Brown skin, right over quadrant pain, arthralgias, fatigue, all that is a secondary hemochromatosis, where we have various tissues with the deposition of the iron, pancreas, heart, and skin are the most common ones to be seen. So with the heart, we have a restrictive cardiomyopathy. With the skin, we have the browner color of the skin. And then the pancreas is where we're getting some of those discomforts, polyurea, elevated glucose levels, and that right upper quadrant discomfort there. If you found this material helpful for your studying, please like and consider subscribing to the channel. Also, share this video so that more people can benefit from it like you have.