Alpha-2-globin gene polyadenylation (AATAAA-->AATAAG) mutation in hemoglobin H disease among Kuwaitis

In the Arabian Gulf region, hemoglobin (Hb) H disease usually results from homozygosity or compound heterozygosity involving the alpha2-globin gene polyadenylation (poly A) signal (AATAAA-->AATAAG) mutation (alpha(T)alpha). Here we document the clinical and hemato logical characteristics of children with Hb H disease being followed in Kuwait.

Twenty-four patients (0.5-12 years old, mean 4.7 +/- 3.5 years) with persistent microcytic, hypochromic anemia (and normal iron status as well as normal Hb A2 levels) were referred to the pediatric hematology clinic for further investigations. They were all screened for the alpha+-thalassemia (alpha+-thal; -3.7 kb) deletion using a standard PCR method. They were also screened for the alpha2-globin gene alpha(T)alpha allele and the 5nt deletion (-alpha5nt) in the first intervening sequence, which are common alpha-thal alleles in this population. They were followed up for periods ranging from 2 to 8 years.

Of the 24 patients, 4 (16.7%) also had sickle cell trait (Hb-AS), while 7 (29.2%) were glucose-6-phosphate dehydrogenase deficient. Only 1 patient had significant hepatosplenomegaly and 1 developed gallstones. While none was on chronic transfusion therapy, 8 (33.3%) had been transfused at least once and, in 3 instances, this was secondary to parvovirus B19 +ve aplastic crisis. The alpha-globin genotype was successfully determined in almost all patients. The results showed that 17 (70.8%) patients were homozygous for the poly A mutation (alpha(T)alpha/alpha(T)alpha), 6 (25.0%) were compound heterozygotes for this and the alpha+-thal (-3.7 kb) deletion (-alpha/alpha(T)alpha) and 1 (4.2%) was undetermined. There were no significant differences in the phenotypes of the 2 genotypes and their hematological features were identical.

Hb H disease involving the poly A mutation is a mild thal intermedia phenotype among Kuwaitis. There are no serious complications and there is no need for regular blood transfusion.