The Genetical Interpretation of Haemoglobin H Disease

Abstract

The clinical and haematological data of nine patients with haemoglobin H disease, as well as of 16 members of their families, are reported. Pedigree study and haematological data permit the assumption that in an individual four genes could be responsible for α-chain synthesis. Based on this hypothesis, four variants of α-thalassaemia are expected to exist. The first, in which only one gene is affected has no, or only minor, red cell changes and an increase in Hb Bart’s at birth, the second with two genes affected has in addition Hb H inclusion bodies in a few red cells, the third, with three genes affected represents haemoglobin H disease, and the fourth, with all four genes affected, represents homozygous α-thalassaemia, which is incompatible with life and results in a stillborn child with hydrops foetalis.

Haemoglobin H Disease and Pregnancy in a Malaysian Woman

“…Genetic evidence suggests that HbH disease results from the interac tion of two a-genes, although whether allelic, closely linked or segregating independently, it is still not clear [7,14]; it is also suggested that three ab normal genes may be involved and HbH disease results when two are pre sent, severity and symptoms depending on the type of gene combination [8]; or that, from one to four genes of the a-thalassaemic type may be in volved, with progressive effects -minimal with one, more pronounced with two, HbH disease with three, and Bart's hydrops with all four [6], The case reported here showed no slow-moving Hb fraction, and is likely to be of the a-thalassaemia-1, 2 doubly-heterozygous type, although there are no family studies to support this. The findings on the blood of the pa tient's husband and baby also do not completely exclude the presence of a minimally expressed a-thalassaemia trait in either.…”

<i>α</i>-Thalassaemia in Cuba

“…gene produces 5% Hb Barts in newborns, whereas the presence of one «-thal2 produces levels of approximately 1 -2 % . Another interpreta tion, based on the duplication of the «-chain locus, which also explains the different types of «-thalassaemia, has been proposed by Kattamis and Lehmann [2], According to this model, the inactivity of one, 2,3 or of all the 4 a-genes is responsible for the various types of the disease.…”

Inheritance of Haemoglobin H Disease

“…Thus, one person could possess 1 to 4 «-thalassaemia genes, which would explain the vari ability in the expression of «-thalassaemia. Kattamis and Lehmann [7] thought that clinical and haematological findings could be classified by the number of «-genes involved: minimal changes when 1 gene is pres ent, more pronounced changes when 2 genes are abnormal, Hb H dis ease when 3 genes are present, and hydrops foetalis when all 4 genes are abnormal. This theory sounds very attractive, especially since Brimhall et al [1] have presented evidence for the presence of 2 a-chain genes in man.…”