Genetic and clinical features of hemoglobin H disease in Chinese patients

Abstract

Background. Normally, one pair of each of the two α-globin genes, α1 and α2, resides on each copy of chromosome 16. In hemoglobin H disease, three of these four α-globin genes are affected by a deletion, a mutation, or both. We studied the α-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 α-globin genes. Results. Hemoglobin H disease in 87 of the 114 patients (76 percent) was due to the deletion of three of the four α-globin genes (--/-α), 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 α-globin genes are deleted and a third is mutated (--/αα(T)). All 87 patients with the deletional type of hemoglobin H were double heterozygotes in whom there was a deletion of both α-globin genes from one chromosome, plus a deletion of the α1 or α2 gene from the other chromosome (--/α- or --/-α). A variety of mutated α-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. (C) 2000, Massachusetts Medical Society.