Genetics and pathophysiology of glucose-6-phosphate dehydrogenase deficiency
- Bertil Glader, MD, PhD
Bertil Glader, MD, PhD
- Professor of Pediatrics
- Stanford University School of Medicine
- Section Editors
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Blood Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Benjamin A Raby, MD, MPH
Benjamin A Raby, MD, MPH
- Section Editor — Genetics
- Associate Professor of Medicine
- Harvard Medical School
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 .
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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- FUNCTION OF G6PD
- GENETICS OF G6PD
- G6PD and its variants
- Classification of G6PD variants
- - Wild-type enzyme
- - G6PD A- variant
- - G6PD Mediterranean variant
- PATHOPHYSIOLOGY OF G6PD DEFICIENCY
- Hemolytic anemia
- Jaundice in neonates
- G6PD in other hematopoietic cells
- Possible protection against malaria
- INFORMATION FOR PATIENTS