Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In contrast to findings in the thalasemia syndromes, studies of globin synthesis in subjects with structurally abnormal hemoglobins have generally revealed equal production of alpha and beta polypeptide chains. However, in the present investigation of globin biosynthesis in vitro in blood and marrow from two subjects heterozygous for unstable hemoglobin Leiden, beta6 or 7 Glu --> O, a significant excess of alpha-chain production was revealed. A mother and daughter of northern European ancestry with mild compensated hemolytic anemia were found to have 25% hemoglobin Leiden. Increased hemolysis occurred after the ingestion of a sulfonamide and during infections. Normal levels of hemoglobin A2, 3.0 and 2.7%, and hemoglobin F, 0.8 and 0.6%, were found in the two subjects. Similar percentages of the minor hemoglobins were demonstrated in other family members without hemoglobin Leiden. After incubation of peripheral blood with [(3)H]-leucine, the beta(A)/beta(Leiden) synthesis ratio was 1.3, and the specific activity of beta(Leiden) was 1.3-2 times beta(A). These results indicate preferential destruction of the unstable hemoglobin Leiden. However, in contrast to previous studies of other unstable hemoglobins, there was excess synthesis of alpha-chains. The total beta/alpha synthesis ratio was 0.47-0.63 in peripheral blood and 0.82 in marrow. A pool of free alpha-chains was demonstrated by starch gel electrophoresis and DEAE column chromatography. The synthesis of globin chains was balanced in family members without hemoglobin Leiden. This degree of predominance of alpha-chain synthesis in subjects with hemoglobin Leiden resembles the findings in heterozygous beta-thalassemia. However, the relatively normal hemoglobin content of the cells with this abnormal hemoglobin suggests the possibility of an absolute excess alpha-chain production in the hemoglobin Leiden syndrome.
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PMID:Imbalance in alpha and beta globin synthesis associated with a hemoglobinopathy. 443 Jul 24

In this report we describe a case of Hb H disease due to the interaction of the --(MED 1) deletion with a new alpha(+)-thalassemia determinant. The molecular analysis of the proband's genomic DNA was carried out by polymerase chain reaction amplification and sequencing of both alpha genes of the alpha(+)-thalassemia chromosome and revealed a deletion of codon 62 of the alpha1 gene. This DNA triplet codes for a valine residue at the E11 alpha helix, which is located in the interior of the heme pocket. Substitutions of valine E11 with other amino acid residues in the alpha as well as beta polypeptide chains lead, in the heterozygous carrier, either to Hb M disease or to congenital non-spherocytic hemolytic anemia. We assume that the deletion of valine at alpha62(E11) disrupts the conformation of the alpha chain to such an extent that the mutated subunit is rapidly removed by proteolysis. The final result is an alpha-thalassemia phenotype rather than an unstable hemoglobin syndrome. This conclusion is supported by the apparent absence of an abnormal alpha chain in the peripheral blood of the patient.
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PMID:Hb Aghia Sophia [alpha62(E11)Val-->0 (alpha1)], an "in-frame" deletion causing alpha-thalassemia. 1056 20