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The molecular basis of chronic granulomatous disease

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Summary and conclusions

CGD is a rare inherited immunodeficiency syndrome, caused by the phagocytes' inability to produce (sufficient) reactive oxygen metabolites. This dysfunction is due to a defect in the NADPH oxidase, the enzyme responsible for the production of superoxide. It is composed of several subunits, two of which, gp9lphox and p22phox, form the membrane-bound cytochrome b558, while its three cytosolic components, p47phox p67phox and p40phox, have to translocate to the membrane upon activation. This is a tightly and intricately controlled process that involves, among others, several low-molecular weight GTP-binding proteins. Gp91phox is encoded on the X-chromosome and p22phox, p47phox and p67phox on different autosomal chromosomes, and a defect in one of these components leads to CGD. This explains the variable mode of inheritance seen in this syndrome.

Clinically CGD manifests itself typically already at a very young age with recurrent and serious infections, most often caused by catalase-positive pathogens.

Modern treatment options, including prophylaxis with trimethoprim-sulfamethoxazole and rIFN-γ as well as early and aggressive anti-infection therapy, have improved the prognosis of this disease dramatically.

CGD, as a very well-characterized inherited affection of the hematopoietic stem cells, is predestined to be among the first diseases to profit from the advances in cutting-edge therapeutics, such as gene therapy and in utero stem cell transplantation.

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  1. Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Plesmanlaan 125, 1066, CX Amsterdam, The Netherlands

    Christof Meischl & Dirk Roos

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Meischl, C., Roos, D. The molecular basis of chronic granulomatous disease. Springer Semin Immunopathol 19, 417–434 (1998). https://doi.org/10.1007/BF00792600

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