Genetic and clinical features of hemoglobin H disease in Chinese patients

N Engl J Med. 2000 Aug 24;343(8):544-50. doi: 10.1056/NEJM200008243430804.


Background: Normally, one pair of each of the two alpha-globin genes, alpha1 and alpha2, 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 alpha1-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 (--/alphaalphaT). 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 alpha1 or alpha2 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • China / ethnology
  • Female
  • Ferritins / blood
  • Gene Deletion*
  • Genotype
  • Hong Kong
  • Humans
  • Infant
  • Infant, Newborn
  • Liver / pathology
  • Liver Function Tests
  • Male
  • Middle Aged
  • Mutation
  • Severity of Illness Index
  • alpha-Thalassemia / blood
  • alpha-Thalassemia / classification
  • alpha-Thalassemia / genetics*
  • alpha-Thalassemia / physiopathology


  • Ferritins