Different Forms of Hb H Disease in the Chinese

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Abstract
A marked genetic and clinical variability of the Hb H syndrome occurs because of the molecular heterogeneity of α-thalassemia (thal). The hallmark is the presence of excess β chains forming Hb H (β tetramer). In the Chinese, classical Hb H disease presents as “α-thalassemia intermedia” and is due to a double heterozygosity for two deletional forms of α-thal, α-thal-1 and α-thal-2. The majority of cases with an α-thal-1 defect have a deletion of at least 18.1 kb starting 3′ to the ζ1 gene which includes the ψα and the two a genes; it is similar to that described in Thais. However, two families had a deletion of the entire ζ-α gene cluster, i.e. ζ-α-thal-1. Of 33 α-thal-2 defects studied, 26 were the rightward deletion (α−3.7 kb, all type I defects) and seven the leftward deletion (α−4.2 kb); one of the latter was associated with Hb Q. About 10% of the α-thal defects belong to the nondeletion type, the most common form being Hb Constant Spring (CS). This anomaly, when coinherited with α-thal-1, produces Hb H-CS disease which has a most marked anemia and splenomegaly due to the instability of the α-CS chain. Hb Quong Sze produces an α-thal-2 because of the unstable α-Quong Sze chain. One patient who inherited classical Hb H disease and Hb New York (NY) [α113(G15)Val→Glu] had severe anemia, and required frequent blood transfusions due to the deleterious effect of an increased α-NY chain turnover. Unlike usual cases of Hb H disease, two patients with the nondeletional form of Hb H had severe anemia during fetal life resulting in hydropic changes (Hb H Hydrops Fetalis). These cases of severe α-thal pose special problems for prenatal diagnosis.