Determination of erythrocyte pyruvate kinase deficiency in Basenjis with chronic hemolytic anemia.

Erythrocyte pyruvate kinase (PK) deficiency was first described in Basenjis 20 years ago. Although the approach to diagnosis had not been well established, a screening program to detect heterozygotes was thought to have eliminated PK deficiency from the Basenjis of the United States. Four not closely related Basenjis with severe chronic hemolytic anemia, from various parts of the United States, were studied. Their PCV ranged from 16 to 25% and their reticulocyte count was always above 15%. A progressive osteosclerosis was seen in all of the Basenjis and hepatic failure developed in 2 of them. The erythrocyte intermediary metabolite patterns indicated a glycolytic defect at the PK step. Erythrocyte PK activities were markedly increased in the anemic Basenjis, compared with those of a control group, but the enzyme in these Basenjis had abnormal kinetic properties and was thermolabile. An antibody against R-type PK, the regular erythrocyte PK form, did not neutralize the PK activity of affected Basenjis, and results of electrophoretic studies suggested the expression of M2-type PK, a leukocyte and fetal erythroid PK-type. Clinically healthy heterozygous Basenjis had half-normal R-type PK activity and did not express the M2-type in their erythrocytes. We conclude that severe chronic hemolytic anemia, caused by erythrocyte PK deficiency, and associated osteosclerosis still develop in Basenjis. A definitive diagnosis cannot be reached by simply measuring erythrocyte PK activity; rather, diagnosis requires measurement of glycolytic substrate accumulation and enzyme stability and immunologic or electrophoretic studies of erythrocyte PK.