Hereditary Non-spherocytic Hemolytic Anemia of the Pyruvate-kinase Deficient Type

Abstract

Non-spherocytic hemolytic anemia was investigated in five severely affected Amish children. The hemolytic syndrome appeared in the fourth generation of related families, and was transmitted as a Mendelian autosomal recessive trait. Siblings in whom the disease was previously unrecognized died in early infancy. The affected children exhibited pallor, icterus, and splenomegaly by three to 24 months of age. Osseous thickening resulted in prominent frontal bosses. Immuno-hematologic procedures excluded extra-corpuscular immune mechanisms and the intrinsic red cell defect of paroxysmal nocturnal hemoglobinuria. Autohemolysis at 48 hours upon blood from each anemic subject was increased and could be diminished only by addition of glucose, but was decreased to normal amounts by providing adenosine triphosphate, and was diagnostic of a type II variant. Erythrocyte glucose-6-phosphate dehydrogenase and glutathione content after acetylphenyl-hydrazine was normal but pyruvate kinase was profoundly deficient in erythrocytes of all homozygous affected children. Each of their parents possessed intermediate levels of intraerythrocyte pyruvate kinase, and were heterozygotes for this recessive gene. Mean cell life, determined after splenectomy, was between 12 - 13.1 days, in affected siblings, and in one infant there was increased localization of Cr-51 labelled autogenous red cells measured in splenic tissue, at splenectomy. The non-spherocytic hemolytic anemias are not a homogenous group of diseases, although among their type II variants they are closely but not completely identical, and are by past reports customarily unimproved by splenectomy. In some type II variants, with pyruvate kinase deficiency of their erythrocytes, limited splenic sequestration or selective splenic "stressing" of red cells with a defect in glycolysis may occur, and in such instances splenectomy yields unequivocal palliation.