CONGENITAL 6-PHOSPHOGLUCONATE DEHYDROGENASE (6PGD) DEFICIENCY ASSOCIATED WITH CHRONIC HEMOLYTIC-ANEMIA IN A SPANISH FAMILY

Clinical and metabolic studies were performed in four members of a Spa nish family with partial (50%) 6 phosphogluconate dehydrogenase (6PGD) deficiency. In all cases the activities of 6 phosphogluconolactone (6 PGL) and glutathione reductase (GR) were normal, and the molecular cha racterization performed in the partially purified 6PGD from the propos itus showed normal kinetic and electrophoretic patterns. Two females ( the propositus and her sister) suffered from a well-compensated chroni c nonspherocytic hemolytic anemia (CNSHA) and exhibited decreased RBC glutathione (GSH) stability with increased oxidative susceptibility, d efined by enhanced malonyldialdehyde (MDA) generation ''in vitro.'' Th e other two members of the family (the propositus's mother and brother ) were clinically asymptomatic. In the propositus and her sister, RBC metabolism exhibited a markedly abnormal concentration of glycolytic i ntermediates, mainly characterized by striking increases in fructose 1 ,6 bisphosphate (50-fold), dihydroxiacetone-phosphate (20-fold) and gl yceraldehyde 3-phosphate (tenfold). Although the precise mechanism of the hemolysis in the two patients is unknown, the enhanced oxidative t hreat observed in their RBCs may interfere in some way with the glycol ytic pathway function, leading to a marked increase in certain metabol ic intermediates located before the glyceraldehyde 3 phosphate dehydro genase (GA3PD) step. Since it seems that GA3PD half-life is modulated by fluctuations of the cytosolic redox status, an ''in situ'' approach was simulated by using permeabilized RBCs. In these conditions, GA3PD activity was significantly lower in the propositus and her sister tha n in the asymptomatic members of the family and the simultaneous norma l control. (C) 1996 Wiley-Liss, Inc.