A New Genetic Basis for Hemoglobin-H Disease

We studied 11 families with α-thalassemia from the Qatif oasis population of eastern Saudi Arabia to determine the genetic and molecular basis of hemoglobin-H disease, which is being encountered in this area with increasing frequency. The results show that there are two common α-thalassemia haplotypes, a deletion (–α/) determinant and a nondeletion (ααT/) determinant, which interact to produce a series of overlapping phenotypes. The most severe, hemoglobin-H disease, results from the homozygous state for the nondeletion determinant — a pattern of inheritance not previously recognized for this condition. Its molecular and genetic properties are thus different from those that produce the condition in Oriental or Mediterranean populations. (N Engl J Med. 1980; 303:1383–8.) HEMOGLOBIN-H disease, clinically the most important form of α-thalassemia, is a chronic hemolytic anemia found commonly in the Orient and Mediterranean. It results from an inherited defect in the synthesis of the α chains of hemoglobin.1 The genetic characteristics of α-thalassemia in these populations have been well characterized, although it is becoming clear that the underlying molecular basis of the disease is more complex than has been previously recognized.2 In Saudi Arabia α-thalassemia is extremely common, 3 but its pattern of inheritance and that of hemoglobin-H disease, which is being encountered in the eastern-oasis populations with increasing frequency, 4,5 has remained unresolved. . . © 1980, Massachusetts Medical Society. All rights reserved.