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Siler, Ulrich; Romao, Susana; Tejera, Emilio; Pastukhov, Oleksandr; Kuzmenko, Elena; Valencia, Rocio G.; Spaccamela, Virginia Meda; Belohradsky, Bernd H.; Speer, Oliver; Schmugge, Markus; Kohne, Elisabeth; Hoenig, Manfred; Freihorst, Joachim; Schulz, Ansgar S.; Reichenbach, Janine (2017): Severe glucose-6-phosphate dehydrogenase deficiency leads to susceptibility to infection and absent NETosis. In: Journal of Allergy and Clinical Immunology, Vol. 139, No. 1: pp. 212-219
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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorderof red blood cells in human subjects, causing hemolytic anemia linked to impaired nicotinamide adenine dinucleotide phosphate (NADPH) production and imbalanced redox homeostasis in erythrocytes. Because G6PD is expressed by a variety of hematologic and nonhematologic cells, a broader clinical phenotype could be postulated in G6PD-deficient patients. We describe 3 brothers with severe G6PD deficiency and susceptibility to bacterial infection. Objective: We sought to study the molecular pathophysiology leading to susceptibility to infection in 3 siblings with severe G6PD deficiency. Methods: Blood samples of 3 patients with severe G6PD deficiency were analyzed for G6PD enzyme activity, cellular oxidized nicotinamide adenine dinucleotide phosphate/NADPH levels, phagocytic reactive oxygen species production, neutrophil extracellular trap (NET) formation, and neutrophil elastase translocation. Results: In these 3 brothers strongly reduced NADPH oxidase function was found in granulocytes, leading to impaired NET formation. Defective NET formation has thus far been only observed in patients with the NADPH oxidase deficiency chronic granulomatous disease, who require antibiotic and antimycotic prophylaxis to prevent life-threatening bacterial and fungal infections. Conclusion: Because severe G6PD deficiency can be a phenocopy of chronic granulomatous disease with regard to the cellular and clinical phenotype, careful evaluation of neutrophil function seems mandatory in these patients to decide on appropriate anti-infective preventive measures. Determining the level of G6PD enzyme activity should be followed by analysis of reactive oxygen species production and NET formation to decide on required antibiotic and antimycotic prophylaxis.