 So, for alpha thalassemias, alpha thalassemia is a deletion on chromosome 16. You can see several different types of alpha thalassemias, and we'll discuss those here in just a minute. There are two different types of deletions that you can have as well on a minor thalassemia, and those are cis deletions and trans deletions. The cis deletion, which means it's on the same chromosome, are often seen in Asian populations. And then the trans deletions, where it's on an opposite chromosome, all on chromosome 16, are often seen with African Americans. So let's look at the four different types of alpha thalassemias. So first to start off, your normal genetic makeup is the four alpha chains. If you are missing one of those alpha chains, that is an alpha thalassemia minima. This basically is going to be silent. It is someone that is a carrier and a carrier only, and they typically don't show any symptoms. When we move to deleting two of the alpha chains, you can have trans. See here where this is on two different chromosomes. Or you can have cis, where it is on the same chromosome. Both of these translate into an alpha thalassemia minor, and your symptoms are usually mild. It gets you a mild, microcytic, hypochromic anemia, and that's about all you deal with. When you delete three of these chains, and you are left with only one alpha chain, that is HBH disease, or hemoglobin H disease. This gives you a moderate to a severe microcytic and hypochromic anemia. And when all of your alpha chains are deleted, that is known as HB-Barts, or hemoglobin-Barts disease, and that is not compatible with life, causing hydrops phitalis. Of note, during hemoglobin-Barts disease, during the fetal stage, before the spontaneous abortion can occur, we do see an increase in the gamma globulin genes. Alright, let's move on and discuss beta thalassemias. Beta thalassemias are a chromosome 11 point mutation, and it's often seen in Mediterranean populations. There are two different types of beta thalassemias, major and minor. In the beta thalassemia minor, you're just seeing the beta chain is underproduced, and it is often usually asymptomatic. You don't see a lot of symptoms with this due to missing one beta chain. For beta thalassemia major, you have the beta chain is completely absent. In a peripheral smear, you're going to see target cells and anisopoichlocytosis. For the target cells, that is often seen in liver disease, post splenectomy, thalassemias and hemoglobin C, as well as our beta thalassemia. For the anisopoichlocytosis, what that term means is a variance in shape and size of the red blood cell. This variance will require blood transfusions to correct any issues with. You'll see on X-ray a crew cut skull. This crew cut skull is due to a marrow expansion for creating more blood cells when the marrow expands because of the poor red blood cells that are produced. We also do see hepatosplenomegaly, and as you can see here in this photo, this is a picture of a spleen that was removed from a child. The spleen is grossly enlarged due to the poor red blood cells due to his beta thalassemia. There is also an increased risk of parbo B19 induced aplastic crisis. Mostly this is going to be due to the spleen not functioning correctly. The spleen does help reduce the risk of parbo B19 problems. Your fetal hemoglobin is increased during the first six months of life, and that is actually protective of the disease with beta thalassemias. After those first six months, you do lose some of that protection and will require a treatment of blood transfusions, and the only curative treatment is your bone marrow transplant. Moving on to lead poisoning. Lead poisoning will cause a decrease in heme synthesis that is because of the inhibition on the ALAD hydrogenase and the ferrochilatase enzymes. You'll also see ribosomal RNA degradation being reduced with lead poisoning, and this causes basophilic stippling, which we'll see a picture of here in just a moment. The symptoms for lead poisoning spell out LEAD, and these symptoms are lead lines on the gingiva, which are Burton lines, and then you have lines of lead on the long bones. So as you can see over here in this x-ray, those are lead lines that are indicative of lead poisoning. The E in lead symptoms is encephalopathy, as well as erythrocyte basophilic stippling. You can see at the head of these arrows over here, the basophilic stippling A in lead poisoning symptoms is abdominal colic and cideroblastic anemia, which we will discuss here in just a few moments. The D is drop, so you have wrist drop and foot drop. We do discuss dimer caprol as well as EDTA as the first line treatments for lead poisoning, and a line to remember is that it sucks to be a kid who eats lead. This leads to succimer, which is used for chelation in children. Oftentimes, lead poisoning is seen in older homes prior to the 1970s in the paint. The paint will chip off, the children will eat the lead, and then that can cause lead poisoning. Some cheap toys as well is often seen with lead poisoning, although the new regulations have decreased that significantly. Moving on to cideroblastic anemia. Cideroblastic anemia has three different causes. The first is genetic, and this is an X-linked defect in the ALA synthase. It can be acquired in a myelodysplastic syndrome, or it can be a reversible cause of the cideroblastic anemia, which is most commonly due to alcohol. This can also be seen with lead poisoning, as I just mentioned. And B6 deficiency, copper deficiency, drugs such as isoniazid or lenezolid can also cause a cideroblastic anemia, so don't always assume that it's alcohol because there are multiple potential causes for a cideroblastic anemia. Looking at the labs for cideroblastic anemia, the iron is going to be increased. Your total iron binding capacity is normal to a decreased level, and your ferritin is increased. Using a Prussian blue stain, we see a ring cideroblast, as you can see here in this picture. There's a ring around that cell. And on a peripheral smear, that is where we see the basophilic stippling that we saw on the previous slide. The treatment for cideroblastic anemia is pyridoxine. Pyridoxine is also known as vitamin B6, and that is actually a cofactor in the ALA synthase, which as we discussed above, the genetic factor of an X-linked issue in the ALA synthase gene.