Genetic and clinical features of hemoglobin H disease in Chinese patients

Background: Normally, one pair of each of the two alpha-globin genes, alpha 1 and alpha 2, resides on each copy of chromosome 16. In hemoglobin H disease, three of these four alpha-globin genes are affected by a deletion, a mutation, or both. We studied the alpha-globin gene abnormalities and the clinical and hematologic features of Chinese patients with hemoglobin H disease in Hong Kong. Methods: We assessed the clinical features, hematologic values, serum ferritin levels, and liver function of 114 patients with hemoglobin H disease. We also performed echocardiography and magnetic resonance imaging of the liver and examined the two pairs of alpha-globin genes. Results: Hemoglobin H disease in 87 of the 114 patients (76 percent) was due to the deletion of three of the four alpha-globin genes (--/-alpha), a combination termed the deletional type of hemoglobin H. The remaining 27 patients (24 percent) had the nondeletional type of hemoglobin H disease, in which two alpha-globin genes are deleted and a third is mutated (--/alpha alpha(T)). All 87 patients with the deletional type of hemoglobin H were double heterozygotes in whom there was a deletion of both alpha-globin genes from one chromosome, plus a deletion of the alpha 1 or alpha 2 gene from the other chromosome (--/alpha- or --/-alpha). A variety of mutated alpha-globin genes was found in the patients with nondeletional type of hemoglobin H disease. Patients with the nondeletional type of the H disease had more symptoms at a younger age, more severe hemolytic anemia, and larger spleens and were more likely to require transfusions than patients with deletional hemoglobin H disease. The severity of iron overload was not related to the genotype. Conclusions: Chinese patients in Hong Kong with the nondeletional type of hemoglobin H disease have more severe disease than those with the deletional type of the disease. Iron overload is a major cause of disability in both forms of the disease. (N Engl J Med 2000;343:544-50.) (C)2000, Massachusetts Medical Society.