Hereditary Hemolytic Anemia Associated with Glucosephosphate Isomerase (GPI) Deficiency— a New Enzyme Defect of Human Erythrocytes

Abstract

A new congenital hemolytic anemia not characterized by spherocytosis has been defined as due to a deficiency in another glycolytic enzyme, glucosephosphate isomerase, the catalyst specific for the second step of the Embden-Meyerhof glycolytic pathway. The leukocytes and the plasma are involved as well as the erythrocytes, but there is no clinical evidence of dysfunction other than the hemolytic anemia. Family studies are consistent with an autosomal-recessive mode of inheritance with the asymptomatic heterozygotes demonstrating an intermediate enzyme deficiency, and the symptomatic homozygote, the propositus, demonstrating a marked enzyme deficiency.

Combined Glucosephosphate Isomerase and Glucose‐6‐Phosphate Dehydrogenase Deficiency of the Erythrocytes: A New Haemolytic Syndrome

“…Autohaemolysis is only slightly increased beyond normal and partly corrected by glucose and neutralized ATP. A similar autohaemolysis pattern has been observed in haemolytic disorders associated with hexokinase (Valentine et al, 1967), G6PD (Dacie, 1968) and GPI (Baughan et al, 1968) deficiency. The reason for the typical autohaemolysis pattern in these enzyme defects is not known at present, but it is of interest that these three defects with type I autohaemolysis produce metabolic defects in the early stages of red cell glucose metabolism.…”

“…Thc low ATP level is in accordance with this assumption. Thus, the same mechanism as proposed by Baughan et al(1968) in GPI deficiency may operate in this case with GPI and G6PD deficiency: the young cells may survive for a certain time utilizing metabolic processes which will soon be largely lost, for example hexokinase and G6PD activity, and GPI deficiency, though still compatible with survival and even an effective function in young cells, may become crucial and fatal as the cell matures.…”

“…propositus is similar to the case described by Baughan et a1 (1968). The mode of inheritance seems to be autosomal recessive as in the two kindreds of Baughan et al(1968) and Paglia et al(1969). Only the propositus, homozygous for GPI deficiency, has a chronic haemolytic process since early childhood with the features of nonspherocytic haemolytic anaemia.…”

Erythrocyte Enzymatic Abnormalities in HEMPAS (Hereditary Erythroblastic Multinuclearity with a Positive Acidified‐Serum Test)

“…The blood samples were kept chilled in ice, in transit from Toronto to Los Angeles; a normal control blood was includcd in each package. The activity of enzymes of the Embden-Meyerhof and hexose nionophosphate shunt (HMP) pathways, as well as those of certain non-glycolytic enzymes, were assayed by methods previously described (Tanaka et al, 1962;Koutras et al, 1964;Schneider et af, 1965;Paglia & Valentine, 1967;Valentine et a!, 1967Valentine et a!, , 1969Valentine et a!, , 1970Baughan et a!, 1968). Erythrocyte glutathione (GSH) was also measured.…”

Haemolytic Anaemia Associated with Glucosephosphate Isomerase (GPI) Deficiency in a Black South African Child

“…These have been shown to have low temperature stabilities and generally different electrophoretic mobilities (Paglia & Valentine, 1974). In most instances, the GPI activity is also decreased in leucocytes, platelets and fibroblasts (Baughan et al, 1968;Paglia et al, 1969;Cartier et al, 1969). The present report describes the clinical, haematological and biochemical findings in a Black South African child with chronic haemolytic anaemia associated with GPI deficiency.…”