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.     

A new glucose-6-phosphate dehydrogenase variant (G-6-PD Kalyan) found in a Koli family

Summary A new Indian variant of erythrocytic glucose-6-phosphate dehydrogenase (G-6-PD) has been detected in a Koli male subject during population genetic studies. The enzyme variant is characterized by mild enzyme deficiency, slow electrophoretic mobility, low K_m for G-6-P, increased 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 G-6-PD Kalyan. The family history and routine hematological studies did not reveal any evidence that the G-6-PD Kalyan is associated with any hematological abnormalities or clinical symptoms.     

Molecular characterisation of the glucose-6-phosphate dehydrogenase (G6PD) Ferrara II variant

During the last ten years, molecular biological techniques such as cloning and sequencing and, more recently, polymerase chain reaction (PCR) amplification have led to the identification of the molecular defects responsible for more than fifty glucose-6-phosphate dehydrogenase (G6PD) variants. In this paper, we report the identification of the molecular abnormality underlying the G6PD Ferrara II variant, present in the Po delta area of Northern Italy. Biochemical characterisation shows an enzymatic activity of about 15% of normal (WHO class III), slow electrophoretic mobility, low Km for G6P, high percentage substrate analogue utilisation and a biphasic pH optimum curve. After PCR amplification, non-radioiso-topic single-strand conformation polymorphism analysis carried out for the entire coding region has revealed a mobility shift in exon 8. Nucleotide sequencing has demonstrated a missense 844 G>C mutation, causing an Asp>His amino-acid replacement, known as being responsible for G6PD Seattle, G6PD Modena and G6PD Lodi.     

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 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.     

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.