Polycythaemia associated with homozygosity for the abnormal haemoglobin Sherwood Forest (β104 (G6) Arg → Thr)

Abstract

We describe a 22-year-old Pakistani male with polycythaemia associated with homozygosity for a high-affinity haemoglobin mutant, Hb Sherwood Forest. This haemoglobin variant has an amino acid substitution in the beta globin chain at position 104, Arg-->Thr. In the two previously reported instances of this haemoglobin mutant the individuals were heterozygotes and were haematologically normal. We show here that the homozygous state for the mutation is associated with a compensatory erythrocytosis resulting from decreased delivery of oxygen to the tissues. A family study showed that both parents and two siblings are heterozygotes for the haemoglobin mutant and are haematologically normal. To our knowledge, this represents the first example of a beta-globin mutation producing polycythaemia in homozygotes but not in heterozygotes.

Substitution of the Heme Binding Module in Hemoglobin α- and β-Subunits

“…3 According to the x-ray crystallographic study of hemoglobin, the side-chain of Arg(G6) is located on the protein surface of the ␤-subunit, and it does not directly contribute to the heme contact. The mutation at the G6 position, as found in the abnormal hemoglobin, Hb Sherwood Forest, has minor effects on the stability of the globin structure (69), although its oxygen affinity is slightly higher than that of normal hemoglobin (70). In fact, Glu(G6) is also found in other globins such as mammalian myoglobin.…”

Heterozygous Hemoglobin Sherwood Forest Causing Polycythemia

“…Nearly two decades later, Williamson et al described a young man with polycythemia who was found to be homozygous for the same high-affinity hemoglobin [6]. This was the first reported case of homozygous Hb Sherwood Forest, and it showed that homozygotes had impaired oxygen delivery with a compensatory erythrocytosis.…”