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Related disorders of the hexose monophosphate shunt and glutathione metabolism

INTRODUCTION

The red blood cell is protected from oxidant injury via enzymes of the hexose monophosphate (HMP) shunt pathway and those of the glutathione synthetic and metabolic pathways. The most common abnormality in this system is glucose-6-phosphate dehydrogenase deficiency, which can lead to varying degrees of hemolysis. (See "Genetics and pathophysiology of glucose-6-phosphate dehydrogenase deficiency" and "Clinical manifestations of glucose-6-phosphate dehydrogenase deficiency" and "Diagnosis and treatment of glucose-6-phosphate dehydrogenase deficiency".)

Abnormalities have been reported in several of the other enzymes in these pathways, some of which are associated with increased red cell destruction (hemolysis). These disorders will be reviewed here.

6-PHOSPHOGLUCONATE DEHYDROGENASE DEFICIENCY

The enzyme 6-phosphogluconate dehydrogenase (6PGD) catalyzes the conversion of 6-phosphogluconate to ribulose-5-phosphate and carbon dioxide; in the process NADPH is generated from NADP. Initial observations suggested that 6PGD deficiency does not alter red cell survival, presumably because NADPH is also generated by the proximal enzyme, glucose-6-phosphate dehydrogenase (G6PD). (See "Genetics and pathophysiology of glucose-6-phosphate dehydrogenase deficiency".)

As an example, a mutant "Whitechapel" 6PGD has been described, transmitted as an autosomal recessive trait. Heterozygotes and homozygotes had 50 and 2 to 5 percent of normal enzyme activity, respectively [1]. Neither heterozygotes nor homozygotes demonstrated clinical or hematologic abnormalities [2].

However, compensated hemolysis with episodic jaundice and possible oxidant sensitivity has been described in combination with partial 6PGD deficiency in two families [3,4].

        

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Literature review current through: Oct 2014. | This topic last updated: Jan 6, 2014.
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