[Hemoglobinopathy in Japan: detection and analysis].

By means of systematic abnormal Hb surveys of people living in eight districts (Okayama, Shimane, Kagawa, Hyogo, Osaka, Nara, Aichi, and Yamanashi Prefectures) using isoelectric focusing, the number of abnormal Hbs discovered and identified among 301,190 subjects was 128. The frequency was estimated to be about one per 2,350. Recently, however, abnormal Hb carriers have been found among individuals with high or low levels of Hb A1c or with an abnormal HPLC pattern. These carriers were found when glyco-HPLC was used to determine the HbA1c level for detection and diagnosis of diabetes mellitus in physical check-ups of inhabitants in each prefecture. To date, 1,227 cases of abnormal Hbs have been detected by isoelectric focusing and glyco-HPLC. These Hbs were analyzed by protein chemistry and DNA analytical methods. The most typical Hbs found in Japan have been Hb J-Cape Town (an alpha-chain variant) and Hb Riyadh (a beta-chain variant). Homozygotes for Hb J-Cape Town, Hb Ube-2, Hb Hamadan, Hb G-Szuhu and Hb Takamatsu have been discovered among abnormal Hb carriers. The carriers of Hb M-Hyde Park and Hb Koln, which cause hemolytic anemia due to their molecular instability, have been found in some parts of Japan, but by clinical examination rather than by Hb survey. On the other hand, alpha- and beta-thals have often been detected in blood samples with a high or low HbA2 level or in abnormal Hb such as Hb H, during systematic surveys for abnormal Hb. Peripheral blood examinations of these patients revealed typical data, a low MCV, MCH, and sometimes low Hb levels. The diagnosis was made by DNA analyses of the nucleotide sequencing of the beta-globin gene for beta-thals and of the alpha-globin gene arrangement for alpha-thals. beta-Thals found in Japanese mainly involve a point mutation, such as-31CapA-->G(in ATA box) and beta 90 codon GAG-->TAG(creation of a stop codon). The alpha-thals had genotypes of -alpha 3.7/alpha alpha for alpha-thal-2, -SEA/alpha alpha for alpha-thal-1 and -SEA/-alpha 3.7 for Hb H disease.