A phosphoglycerate kinase variant, PGK Uppsala, associated with hemolytic anemia.

An X-linked PGK deficiency is known to be associated with chronic nonspherocytic hemolytic anemia and mental disorders in man. The glycolytic intermediates and red cell enzymes of a Swedish male subject with these genetic abnormalities were examined. The PGK activity of red blood cells from the subject was about 10% of normal, although the activities of other red cell enzymes were normal or above normal. Significant accumulation of 2,3-DPG and 2-phosphoglycerate in the subject's red cells was observed. The PGK from the subject was associated with lower affinity to both ATP and 3-phosphoglycerate and with an increased rate of degradation in red cells and also in vitro. The immunological neutralization test suggested that the specific enzyme activity of the variant enzyme was significantly lower than normal. The variant enzyme moved faster than the normal toward the anode in starch-gel electrophoresis. These results indicate that the variant is a result of structural mutation, and it is designated PGK Uppsala.