Leucocyte glucose-6-phosphate dehydrogenase (G-6-PD) activity in G-6-PD deficient Chinese

The activity of glucose-6-phosphate dehydrogenase (G-6-PD) in leucocytes was studied for erythrocyte G-6-PD deficiency using 49 hemizygous males, 16 heterozygous females, and 19 normal controls. The mean G-6-PD activity in leucocytes of the affected neonates (9.2 +/- 5.4 units) and the children (11.2 +/- 5.3 units) were significantly lower than those of normal newborns (22.9 +/- 5.1 units, P less than 0.01). Seventy percent of the effected newborns and 58% of the children with G-6-PD deficiency had the leucocyte enzyme activity of less than 13 IU/10(9)WBC. The leucocyte enzyme activity (14.6 +/- 8.6 units) of 16 heterozygous G-6-PD deficient mothers was also lower than that of normal controls (23.1 +/- 7.0 units). The present study thus concludes that, in G-6-PD deficient Chinese, the enzyme defect is demonstrable not only in erythrocytes but also in leucocytes.     

GD (-) Aachen,a new variant of deficient glucose-6-phosphate dehydrogenase

Summary A deficient G-6PD variant was discovered in 4 males of one family from north-western Germany. Five generations of this family could be studied.The deficient G-6PD was a new variant, called Gd (-) Aachen. Its main characteristics are the following: severe enzyme deficiency in erythrocytes (3% of normal), contrasting with an almost normal activity in leukocytes; normal molecular specific activity (i.e., normal ratio enzyme activity/cross-reacting material); slow mobility in starch gel electrophoresis (92–94% of normal); increased Michaelis constant for glucose-6-phosphate (60–70 M) and NADP⁺ (20–25 M); decreased inhibition constant by NADPH with respect to NADP⁺ (7 M); increased inhibition by ATP; normal utilization of the substrate analogues; slightly biphasic pH curve; thermal instability, and normal activation energy of the enzymatic reaction.The relationships between the hematologic disorders (severe and frequent hemolytic crises) and the unfavorable kinetic modifications are discussed.with the technical assistance of Joelle Marie and Dominique CottreauDedicated to Prof. Dr. H. Schonenberg, Aachen, on his 60th birthday. The first results of this work were presented in part at the Kongress der Deutschen Kinderärzte, München.     

A new glucose-6-phosphate dehydrogenase variant with congenital nonspherocytic hemolytic anemia (G6PD Genova)

Summary A new deficient variant of glucose-6-phosphate dehydrogenase (G6PD) causing severe congenital nonspherocytic hemolytic anemia (CNSHA) is described. The variant enzyme, characterized by slow electrophoretic mobility, extreme in vivo and in vitro lability, high K_m for G6P and strongly acidic pH optimum, appears to be unique, and has been designated G6PD Genova. Investigation of an obligate heterozygote using various cytochemical, biochemical and recombinant-DNA techniques showed G6PD mosaicism in the erythrocytes and leukocytes. Therefore, the presence of a disadvantageous mutation at one Gd locus did not determine selection in favor of the normal allele in the heterozygote's hemopoietic cells.     

A new glucose-6-phosphate dehydrogenase variant (G6PD Tsukui) associated with congenital hemolytic anemia

Summary A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was found in a 20-year-old Japanese male who showed mild hemolysis after an upper respiratory tract infection. The patient had been noted to have jaundice and reticulocytosis several times before this episode. The enzyme activity of the variant was 1.5% of normal. The enzymatic characteristics were slow anodal electrophoretic mobility, high Km G6P, normal Km NADP, decreased heat stability, and a normal pH optimum. From these results, the enzyme was considered to be a new class 1 variant and was designated G6PD Tsukui.     

A new glucose-6-phosphate dehydrogenase variant (G6PD Nagano) associated with congenital hemolytic anemia

Summary A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was reported. The patient, a 6-year-old Japanese male, was noticed to have hemolytic anemia soon after birth, and a diagnosis of G6PD deficiency was made at the age of 2. He had episodes of hemolytic crisis several times after upper respiratory infection. G6PD activity of the patient was 5.5% of normal. The enzymatic characteristics were examined when he was 5 years old, and his G6PD showed faster-than-normal electrophoretic mobility, low Km G6P, high Km NADP, low Ki NADPH, normal utilization of substrate analogues, heat instability, and a normal pH optimum curve. From these results, this was considered to be a new variant and was designated G6PD Nagano. Infection-induced hemolysis and chronic hemolytic anemia seem to be due to markedly impaired enzyme activity and thermal instability.     

Gd(-) Rennes a new deficient variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia found in France

Summary A new variant of G6PD with total enzyme deficiency associated with nonspherocytic hemolytic anemia in a 60 year old Frenchman is characterized. Partially purified enzyme revealed slow electrophoretic mobility, decreased G6P affinity, thermal instability, abnormal pH curve with a single peak at pH 5.0, abnormal utilization of 2-deoxy-G6P and deamino NADP. This variant differs from all previously reported variants associated with chronic nonspherocytic hemolytic anemia. Accordingly this variant is designated Gd(-) Rennes.     

G-6PD "ankara". a new G-6PD variant with deficiency found in a Turkish family.

A new G-6PD varient with enzyme deficiency is described in a 7-month-old Turkish boy without any hemolytic manifestation, except neonatal hyperbilirubinemia. The main characteristics of this variant were the following: Severe enzyme deficiency in erythrocytes (8% of normal), fast starch-gel-electrophoretic mobility (110% of normal), increased Ki NADPH with respect to NADP+, slightly biphasic pH curve, enzyme instability, in vivo and in vitro, decreased molecular specific activity (58% of normal).     

G6PD Vientiane: A new glucose-6-phosphate dehydrogenase variant with increased stability

Summary A new G6PD variant, called G6PD Vientiane, has been discovered in a patient from Laos.The characteristics of this variant are: mild enzyme deficiency (about 50% of the normal activity) in the granulocytes and the red cells, with normal G6PD-related antigen concentration; increased stability; normal Km glucose 6-phosphate and NADP⁺; increased inhibition constant by NADPH; decreased inhibition by ATP; slightly increased utilization of the substrate analogue; abnormal pH curve, with maximum activity at pH 9.5; slightly reduced starch gel electrophoretic migration. The implications of the molecular stability of a deficient mutant variant are discussed.     

Gd (+) Laguna,a new rare glucose-6-phosphate dehydrogenase variant from Brazil

Summary A new G6PD variant, designated Gd (+) Laguna, was found in a 9-year-old Brazillian boy of Portuguese ancestry suffering from an iron-refractory anemia. The red cell enzyme activity of the subject was 64%. The mutant enzyme showed slower electrophoretic mobility, increased affinity for glucose-6-phosphate, decreased affinity for NADP⁺, elevated utilization of substrate analogues, decreased inhibition of NADPH, normal heat stability and a biphasic pH curve. The occurrence of the variant in two non-anemic relatives of the propositus indicates that the association between this G6PD type and anemia may be coincidental.Publication no. 3171 BCR from the Research Institute of Scripps Clinic     

Detection of a new anomalous variant of glucose-6-phosphate dehydrogenase in human erythrocytes]

Kinetic and electrophoretic properties of 230--300 fold purified preparations of glucose-6-phosphate dehydrogenase (G6PD) from red cells of donors and patients with acute drug hemolytic anemia due to G6PD deficiency were studied. A new abnormal variant of G6PD isolated from red cell of a patient with acute drug hemolytic anemia, which was not described in literature, has been discovered. The abnormal enzyme differs from the normal by decreased Michaelis constant for glucose-6-phosphate and nicotinamide adenine dinucleotide phosphate (NADP), by increased utilization of analogues of substrates--2-deoxy-glucose-6-phosphate and particularly deamino-NADP, by low thermal stability, by the character of pH-dependence, by the appearance of a single band of G6PD activity in polyacrylamide gel electrophoresis.     

G6PD Sendagi: A new glucose-6-phosphate dehydrogenase variant associated with congenital hemolytic anemia

A new glucose-6-phosphate dehydrogenase (G6PD) variant associated with chronic nonspherocytic hemolytic anemia was discovered. It was found in a 2-year-old male who had a hemolytic crisis after an upper respiratory tract infection. The enzyme activity of the variant was 8.4% of that of the normal enzyme. The enzymatic characteristics were slower than normal anodal electrophoretic mobility, low Km G6P, normal Km NADP, increased utilization of substrate analogues, high Ki NADPH, decreased heat stability, and an alkaline pH optimum. From these results, this was considered to be a new variant and was designated G6PD Sendagi.