A-Globin chains

Two copies of the a-globin gene are designated a1 and o2. Each can provide a-globin chains that combine with p-globin chains. 

The thalassemias are hereditary hemolytic diseases in which an imbalance occurs in the synthesis of globin chains. As a group, they are the most common single gene disorders in humans. Normally, synthesis of the a- and p-globin chains are coordinated, so that each a-globin chain has a p-globin chain partner. This leads to the forma... 

Thalassemias are hereditary hemolytic diseases in which an imbalance occurs in the synthesis of either a or 3 globin chains. Each thalassemia can be classified as either a disorder in which no globin chains are produced (a0- or p°-thalassemia), or in which some chains are synthesized but at a reduced rate (a+- or p+-thalassemia). [Note In p-thalassemias, synthe sis of p globin chains is decreased or absent, whereas in a-thalassemias, synthesis of a globin chains is decreased or absent.]... 

Hb Bart s. Hb Bart s results from deletion of aU four a-globin genes with the subsequent inability to produce any a-globin chains that leads to failure of synthesis of Hbs A, F, or A2. In the fetus there is an excess of y-globin chains that join together to form unstable tetramers known as Hb... 

One or more abnormal a-globin chains can combine with Hb S. In African-Americans and West Africans the combination of Hb G Philadelphia (a68(E17) " > ) with Hb S is prevalent. HPLC analysis (Figure 31-12, i) on blood samples from these individuals shows at least two major peaks and two smaller peaks. The two major peaks are due to the combination of the normal a-chain with the normal P-chain and the abnormal a-chain with the normal P-chain. The two smaller peaks are due to the combination of the normal a-chain with the abnormal P-chain and the abnormal a-chain with the abnormal P-chain. Electrophoresis at alkaline pH shows major bands in the A and S positions with a minor band in the C position. At acid pH, bands are seen in the A and S positions. CBC analysis gives a slightly decreased Hb level with normal MCV and MCH. a- or p-thalassemia can be co-inherited with Hb G Philadelphia and Hb S. In these cases, CBC analysis results in markedly decreased MCV and MCH with reduced Hb concentration. 

Hemoglobins Havingan Extended a-Globin Chain Due to Mutation of the Chain Termination Codon... 

Characteristics of the more common /3-thalassemia syndromes are summarized in Table 28-4. Not included are two different abnormal heterozygotes. Anemia results from precipitation of excess a-globin chains, premature red cell destruction in bone marrow and the circulation, and deficiency of functional hemoglobin tetramer. /S-Thalassemia major, or Cooley s anemia, occurs when /3-globin synthesis is markedly depressed or absent. The ineffective erythropoiesis causes massive erythroid proliferation, skeletal deformities, and extramedullary erythropoiesis. The usual treatment is frequent blood transfusion. 

An Asian child has severe anemia with prominence of the forehead (frontal bossing) and cheeks. The red cell hemoglobin concentration is dramatically decreased, and it contains only p-globin chains with virtual deficiency of a-globin chains. Which of the following mechanisms is a potential explanation ... 

The continued absorption of iron causes its deposition in various tissues starting with liver and spleen and followed by myocardium. Deposition of iron in the myocardium usually results in death by intractable cardiac failure. Patients suffer from hypoparathyroidism and hypogonadism. Patients with the severe form of thalassemia are more susceptible to bacterial infection, possibly due to the increase in serum iron, which may favor bacterial growth. Iron overload is less common in the adult forms of a-thalassemia. This is most likely the result of a fundamental difference between a and /3-thalassemia. As mentioned, the excess of a-globin chains cannot form viable tetramers and causes red-cell destruction. The excess /3-chains present in a-thalassemia are able to form soluble homodimers and do not precipitate in the bone marrow. This is paralleled in the fetal state when excess y-chains form soluble homodimers. Hence, a-thalassemia is characterized by a severe degree of inefficient erythropoiesis and a milder degree of anemia. 

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