Genetic and clinical features of hemoglobin H disease in Chinese patients.
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.
Chen
F E
FE
Department of Medicine, University of Hong Kong and Queen Mary Hospital, Hong Kong, China.
Ooi
C
C
Ha
S Y
SY
Cheung
B M
BM
Todd
D
D
Liang
R
R
Chan
T K
TK
Chan
V
V
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002681:China / Q000208:ethnology; D005260:Female; D005293:Ferritins / Q000097:blood; D017353:Gene Deletion; D005838:Genotype; D006723:Hong Kong; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012720:Severity of Illness Index; D017085:alpha-Thalassemia / Q000097:blood / Q000145:classification / Q000235:genetics* / Q000503:physiopathology
D005293:Ferritins