Hb Zoeterwoude [β23(B5)Val → Ala)]: A New β-Globin Variant Found in Association with Erythrocytosis

Abstract

We describe the characterization of a new hemoglobin (Hb) variant found in a 77-year-old Dutch woman, suspected of hypoxia-mediated erythrocytosis. The typical blood parameters (Hb 17.3 g/dL; PCV 0.525 L/L; RBC 5.82 × 1012/L) could not be explained by any of the pathological or physiological conditions causing erythrocytosis. The patient was preventively phlebotomized because of intermittent claudication and erythrocytosis. At the hematological and biochemical levels, no anemia or hemolysis were present and no abnormal Hb fractions were detectable on alkaline electrophoresis or high performance liquid chromatography (HPLC). Molecular analysis revealed intact α-globin genes and a heterozygosity for a GT T → GC T transition at codon 23 of the β-globin gene, causing a Val → Ala amino acid substitution. The P50 measured in full blood indicated that this mutant has an elevated oxygen affinity. This is the fourth single nucleotide substitution at codon 23 of the β gene and the second associated with erythrocytosis. Because the family was not available for investigation no information was obtained as to whether the mutation represents a de novo event or was inherited, and might be a more common cause of erythrocytosis in Dutch patients. Considering the relatively high frequency of β-thalassemia (thal) in the large allochthonous population in The Netherlands, combinations of Hb Zoeterwoude and β-thal traits may lead to hemizygosity, with severe hypoxia and erythrocytosis from a few months after birth.