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Genetics and pathophysiology of glucose-6-phosphate dehydrogenase deficiency

Author
Bertil Glader, MD, PhD
Section Editors
Stanley L Schrier, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked disorder, is the most common enzymatic disorder of red blood cells in humans, affecting more than 400 million people worldwide [1-4]. The clinical expression of G6PD variants encompasses a spectrum of hemolytic syndromes. Affected patients are most often asymptomatic, but many patients have episodic anemia, while a few have chronic hemolysis.

With the most prevalent G6PD variants (G6PD A- and G6PD Mediterranean), hemolysis is induced in children and adults by the sudden destruction of older, more deficient erythrocytes after exposure to drugs having a high redox potential (including the antimalarial drug primaquine and certain sulfa drugs) or to fava beans, selected infections, or metabolic abnormalities (table 1). However, in the neonate with G6PD deficiency, decreased bilirubin elimination may play an important role in the development of jaundice (see 'Jaundice in neonates' below) [5,6].

Normal enzyme function and the genetics and pathophysiology of G6PD deficiency, including its possible role in protecting against severe malaria, will be reviewed here. The clinical manifestations, diagnosis, and treatment of this disorder are discussed separately. (See "Diagnosis and management of glucose-6-phosphate dehydrogenase deficiency".)

A historical review of the discovery of this defect, its clinical manifestations, detection, population genetics, and molecular biology, written by Dr. Ernest Beutler, a pioneer in the understanding of this disorder, is available [7].

FUNCTION OF G6PD

Glucose-6-phosphate dehydrogenase catalyzes the initial step in the hexose monophosphate (HMP or pentose phosphate) shunt, oxidizing glucose-6-phosphate to 6-phosphogluconolactone and reducing nicotinamide adenine dinucleotide phosphate (NADP) to NADPH (figure 1). The HMP shunt is the only red cell source of NADPH, a cofactor important in glutathione metabolism.

             

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Literature review current through: Nov 2016. | This topic last updated: Mon Sep 26 00:00:00 GMT+00:00 2016.
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