Transcription
Hey, in the previous video, we started talking about thalassemia. Now let's get into it and let's talk about alpha-thalassemia. Alpha-thal is the topic of today's video. Again, symptoms of anemia: tired and pale, pale and tired. Sometimes I have a murmur; sometimes I have angina, also fatigue, exercise intolerance, etc. As you know from the previous video, LOC Miam is a problem in the globin chain, whether it's alpha or beta; it's kind of similar. So, normal hemoglobin, normal adult hemoglobin, has two alpha subunits and two beta subunits. They are called hemoglobin tetramers. Okay, two alpha and two beta; that's fine. So, thalassemia: a defect in globin chains. That's thalassemia in general, alpha-thal or beta-thal. So, two things will happen: number one, decreased globin synthesis will lead to decreased hemoglobin because hemoglobin consists of heme and globin. Decreased hemoglobin synthesis will lead to a decrease in the number of RBCs, i.e., anemia, because anemia has a low RBC count, low hemoglobin, and hematocrit. That's number one. Number two: when we have a problem in the globin chain synthesis, hemoglobin tetramers will form certain products, okay, will form, and they are insoluble, so they precipitate in the RBCs. Fine. What will happen? This spleen will recognize these abnormal RBCs with the abnormal precipitate and will start destroying the RBCs, leading to RBC hemolysis. The bone marrow will try to respond by producing more RBCs. Unfortunately, I cannot synthesize globin, so I cannot synthesize hemoglobin. I'm not able to do my job in effective erythropoiesis, poor bone marrow. So, thalassemia, be it alpha or beta, two things will happen: number one, I have anemia, one type of anemia, microcytic anemia, and also a problem in the globin gene synthesis will lead to hemolysis and ineffective erythropoiesis.
Let's dig deeper. Alpha-thalassemia is a problem with the alpha chain or the alpha subunit. Okay, chromosome 16 has two copies of the alpha gene at two different loci. So, two times two equals four alpha genes. We have four genes responsible for producing the alpha chain or the alpha subunit. Okay, so if I delete one of these genes, I'll have a problem; if I delete more, I'll have more problems; vitally even more, I'll have more problems. Okay, so the more deleted, the worse the symptoms. Keep that in mind. So, if only one locus is deleted, it's called alpha-thalassemia trait, and it will have one of them will be alpha, alpha; the other will be alpha negative. So, since we have four genes, so it will be like this: two of them are normal, and these others, one has alpha and one is negative. Okay, what are the symptoms? This patient or this kid is completely asymptomatic. Okay, what about if two loci are deleted? We call this alpha-thalassemia minor. It can be either alpha negative, alpha negative, or alpha, alpha negative, negative. What are the symptoms? Asymptomatic, maybe have very mild microcytic anemia. Of course, microcytic anemia has low MCV. Okay, now three loci deleted. Okay, so three of the alpha are deleted, so beta chains will now be unpaired. Okay, before, beta four tetramers. We said when globin chains are deleted, hemoglobin tetramers are formed. In this case, beta four tetramers, they are present in the RBCs but not in the bone marrow. This hemoglobin H or beta four tetramers. What are the symptoms? Moderate to severe hemolytic anemia. So, there are symptoms. Number four, which is the worst of the worst, it's called hemoglobin Bart's, hemoglobin Bart's. Okay, all of the alphas are deleted, so gammas, okay, form tetramers; they're called hemoglobin Bart's, and of course, there is no effective erythropoiesis. Why? This gamma four has very high affinity to oxygen, so I cannot deliver oxygen to tissue since it's bound to the gamma. Okay, that's fine. What are the symptoms? Hydrops fetalis, death in utero. The baby dies in the uterus. So, hemoglobin electrophoresis tells me the percentage of each type of hemoglobin. So, normally we have 97% hemoglobin A, 2% of hemoglobin A2, 1% of hemoglobin F. However, in alpha-thalassemia trait, I'm talking about the trait, okay, 97% hemoglobin A, 2% hemoglobin A2, 1% hemoglobin F. So, in alpha-thalassemia, hemoglobin electrophoresis is completely normal. However, if three genes are deleted, it's called hemoglobin H disease. So, in hemoglobin H disease, what will be the hemoglobin electrophoresis? It will detect hemoglobin H. If four genes are deleted and it's called hemoglobin Bart's, what will be discovered by electrophoresis? The hemoglobin Bart's. So, what's the most common or most accurate test to diagnose alpha-thalassemia trait or alpha-thalassemia in general? It's genetic studies; that's the most accurate. So, alpha-thalassemia is present in African, Mediterranean, and South East Asian populations. Have to match alpha-thalassemia. If only one locus is deleted, asymptomatic, do nothing. Two loci, asymptomatic, mild anemia, decreased MCV, like you have to observe them. Three genes deleted, moderately severe hemolytic anemia; we have to get blood transfusion, have to give them blood. Okay, we try to postpone it until they become adults. Hydrops fetalis, there is nothing you can do to cure it. Unfortunately, unfortunately, no cure. That's it for alpha-thalassemia, and I'll see you next video.