Hb Oita [α45(CE3)His→Pro]: A New Silent Hemoglobin Variant

Abstract

We describe a new α chain variant accidentally found in a 49-year-old female living in Usa City, Oita Prefecture, Japan. An abnormally low Hb A_1c value of 2.5% (normal range: 4.8–6.3%) was found while she was treated with glucocorticoid for Fisher syndrome. The patient was also diagnosed as having an iron deficiency anemia, but otherwise showed a normal hemogram. An abnormal hemoglobin was not detectable by isoelectrofocusing and high performance liquid chromatographic methods, but appeared as a fast-moving α chain abnormality by urea-carboxymethyl cellulose column chromatography of the globin, from which the content of the abnormal hemoglobin was estimated at approximately 20%. The instability test of the hemolysate was normal. Structural studies demonstrated that the abnormal hemoglobin had an amino acid substitution of His→Pro at α45. It is a new variant and was named Hb Oita or α45(CE3) His→Pro. Additionally, sequence analysis showed a nucleotide change from A→C at the second base in the 45th codon of the α2 gene, CAC(His)ČC (Pro). The β/α ratio was 0.51 (normal range: 0.9–1.2). Her mother and a son did not have the abnormal hemoglobin variant; her father was deceased and no sample was available to verify the inheritance of the variant in this kindred.