Hb Oegstgeest [alpha104(G11)Cys-->Ser (alpha1)]. A new hemoglobin variant associated with a mild alpha-thalassemia phenotype.

A microcytic hypochromic anemic state was observed in an 8-year old Black female of Surinam origin during pre-operative Hb S [beta6(A3)Glu-->Val] screening. Her high zinc protoporphyrin (ZPP) level suggested a chronic iron depletion but, in contrast, the high red blood cell (RBC) count (5.85 x 10(12)/L) was indicative of a possible coexisting thalassemia. No abnormal hemoglobin (Hb) bands were present on high performance liquid chromatography (HPLC) or alkaline electrophoresis and the Hb A2 level was normal. Break point polymerase chain reaction (PCR) failed to reveal any of the common alpha-thalassemia (thal) mutations but selective DNA sequencing of both alpha-globin genes disclosed a TGC-->AGC transversion at codon 104 of the alpha1 gene. Cystine at codon 104 is involved in alpha/beta globin contact and has been described to be a critical amino acid of the alpha2 chain when substituted by a tyrosine (Hb Sallanches), inducing Hb H (beta4) disease in the homozygous state. Our heterozygous patient had a moderate anemia of 12.2 g/dL and a borderline haptoglobin suggesting some degree of hemolysis.

A new polyadenylation site mutation associated with a mild beta-thalassemia phenotype.

At least 180,000 autochthonous and allochthonous people are carriers of a large spectrum of hemoglobinopathies in The Netherlands. We describe two cases, the first, a 33-year old Surinamese Creole woman, studied because of an intermediate hemolytic anemia; the second, a couple requesting analysis because of a previously diagnosed carrier state in the male partner, while the carrier state in the pregnant female was uncertain.

Hb zoeterwoude [beta23(B5)Val-->Ala)]: a new beta-globin variant found in association with erythrocytosis.

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.