title: Molecular diagnosis of chronic granulomatous disease.
abstract: Patients with chronic granulomatous disease (CGD) suffer from recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and Salmonella species. CGD is a rare (∼1:250 000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. Molecular diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes, measuring protein expression of NADPH oxidase components and mutation analysis of genes encoding these components. Residual oxidase activity is important to know for estimation of the clinical course and the chance of survival of the patient. Mutation analysis is mandatory for genetic counselling and prenatal diagnosis. This review summarizes the different assays available for the diagnosis of CGD, the precautions to be taken for correct measurements, the flow diagram to be followed, the assays for confirmation of the diagnosis and the determinations for carrier detection and prenatal diagnosis.
authors.affiliation: Deptartment of Blood Cell Research, Sanquin Blood Supply Organization, Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Roos
authors.forename: M
authors.initials: M
authors.lastname: de Boer
mesh_terms: D001424:Bacterial Infections / Q000276:immunology; D001483:Base Sequence; D005260:Female; D015870:Gene Expression; D006105:Granulomatous Disease, Chronic / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D009154:Mutation; D009181:Mycoses / Q000276:immunology; D019255:NADPH Oxidases / Q000235:genetics* / Q000378:metabolism; D010586:Phagocytes / Q000201:enzymology*; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases
keywords: CGD; DHR test; NADPH oxidase; NBT test; mutation analysis
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