tailieunhanh - Chapter 099. Disorders of Hemoglobin (Part 13)

Hemoglobin E HbE (., α2β226Glu - Lys) is extremely common in Cambodia, Thailand, and Vietnam. The gene has become far more prevalent in the United States as a result of immigration of Asian persons, especially in California, where HbE is the most common variant detected. HbE is mildly unstable but not enough to affect RBC life span significantly. The high frequency of the HbE gene may be a result of the thalassemia phenotype associated with its inheritance. Heterozygotes resemble individuals with mild β-thalassemia trait. Homozygotes have somewhat more marked abnormalities but are asymptomatic. Compound heterozygotes for HbE and a β-thalassemia. | Chapter 099. Disorders of Hemoglobin Part 13 Hemoglobin E HbE . a2P226Glu - Lys is extremely common in Cambodia Thailand and Vietnam. The gene has become far more prevalent in the United States as a result of immigration of Asian persons especially in California where HbE is the most common variant detected. HbE is mildly unstable but not enough to affect RBC life span significantly. The high frequency of the HbE gene may be a result of the thalassemia phenotype associated with its inheritance. Heterozygotes resemble individuals with mild 0-thalassemia trait. Homozygotes have somewhat more marked abnormalities but are asymptomatic. Compound heterozygotes for HbE and a 0-thalassemia gene can have 0-thalassemia intermedia or 0-thalassemia major depending on the severity of the coinherited thalassemic gene. The 0E allele contains a single base change in codon 26 that causes the amino acid substitution. However this mutation activates a cryptic RNA splice site generating a structurally abnormal globin mRNA that cannot be translated from about 50 of the initial pre-mRNA molecules. The remaining 40-50 are normally spliced and generate functional mRNA that is translated into 0E-globin because the mature mRNA carries the base change that alters codon 26. Genetic counseling of the persons at risk for HbE should focus on the interaction of HbE with 0-thalassemia rather than HbE homozygosity a condition associated with asymptomatic microcytosis hypochromia and hemoglobin levels rarely 1 g L 10 g dL . Hereditary Persistence of Fetal Hemoglobin HPFH is characterized by continued synthesis of high levels of HbF in adult life. No deleterious effects are apparent even when all of the hemoglobin produced is HbF. These rare patients demonstrate convincingly that prevention or reversal of the fetal to adult hemoglobin switch would provide effective therapy for sickle cell anemia and 0-thalassemia. Acquired Hemoglobinopathies The two most important acquired hemoglobinopathies are .