Hemoglobin M's of the Japanese

Hb M diseases are the most important hemoglobinopathy in Japan. They are Hb M_Iwate disease (in Iwate prefecture and Hokkaido), Hb M_Boston disease (in Osaka), Hb M_Hyde Park disease (in Akita prefecture) and Hb M_Saskatoon disease (in Hida, Ooita prefecture). The hemoglobins of these diseases cover all the variants of Hb M’s brought about by the replacement of the proximal or the distal histidine by tyrosine. The presence of these hemoglobins in blood is demonstrated by the spectroscopic examination of acid metHb type hemolysate, whose absorption curve lacks depression around 600 mμ, which is characteristic of the normal acid methemoglobin. In the methemoglobin derivatives of the Hb M’s pertaining to the amino acid substitution at proximal histidine (Hb M_Iwate and Hb M_Akita) the second peak of their absorption curves (around 500 mμ) is shifted to the side of shorter wave length in comparison with that in the Hb M's relevant to the substitution of the distal histidine (Hb M_Osaka and Hb M_Kurume). Cyanmethemoglobin of the Hb M's of α chain anomaly (Hb M_Iwate and Hb M_Osaka) shows an absorption peak (around 540 mμ) with wide base which is distinctly different in shape from that of cyanmetHb A. By contrast, the absorption curve of the Hb M's of β chain anomaly (Hb M_Akita and Hb M_Kurume) is almost the same as that of cyanmetHb A. The reactivity of methemoglobins with sodium dithionite is slow and incomplete in the Hb M's of α chain anomaly (Hb M_Iwate and Hb M_Osaka) and rapid and nearly complete in the Hb M's of β chain anomaly (Hb M_Akita and Hb M_Kurume). The Hb M's of α chain anomaly are easily demonstrated by direct application of hemolysate (O_2Hb type) to agar gel electrophoresis, but those of β chain anomaly are seldom detectable by this technique unless the hemolysates have been treated preliminarily with ferricyanide. The Hb M's of α chain anomaly (Hb M_Iwate and Hb M_Osaka) cause cyanosis but they are without any significant ill effect on health. On the contrary, those of β chain anomaly (Hb M_Akita and Hb M_Kurume) may bring about clinical manifestaction of mild hemolytic anemia in addition to cyanosis.