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 x 10(12)/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
alpha-globin genes and a heterozygosity for a GTT-->GCT transition at
codon 23 of the
beta-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 beta 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
beta-thalassemia (thal) in the large allochthonous population in The Netherlands, combinations of
Hb Zoeterwoude and beta-thal traits may lead to hemizygosity, with severe
hypoxia and
erythrocytosis from a few months after birth.