title: Focus on FOCIS: the continuing diagnostic challenge of autosomal recessive chronic granulomatous disease.
abstract: Chronic granulomatous disease (CGD) is a primary immunodeficiency of defective neutrophil oxidative burst activity due to mutations in the genes CYBA, NCF-1, NCF-2, and CYBB, which respectively encode the p22-phox, p47-phox, p67-phox, and gp91-phox subunits. CGD usually presents in early childhood with recurrent or severe infection with catalase-positive bacteria and fungi. We present an unusual case of CGD in which Burkholderia cepacia lymphadenitis developed in a previously healthy 10-year-old girl. Flow cytometric analysis of dihydrorhodamine (DHR)-labeled neutrophils performed by a CLIA-approved outside reference laboratory was reported as normal. However, we found that this patient's neutrophil oxidative burst activity in DHR assays was substantially reduced but not absent. A selective decrease in intracellular staining for p67-phox suggested the diagnosis of autosomal recessive CGD due to NCF-2 gene mutations, and a novel homozygous and hypomorphic NCF-2 gene mutation was found. The potential mechanisms for this delayed and mild presentation of CGD are discussed.
authors.affiliation: Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Yu
authors.forename: David K
authors.initials: DK
authors.lastname: Hong
authors.forename: Kira Y
authors.initials: KY
authors.lastname: Dionis
authors.forename: Julie
authors.initials: J
authors.lastname: Rae
authors.forename: Paul G
authors.initials: PG
authors.lastname: Heyworth
authors.forename: John T
authors.initials: JT
authors.lastname: Curnutte
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
mesh_terms: D019121:Burkholderia Infections / Q000150:complications; D016956:Burkholderia cepacia; D002648:Child; D002869:Chromosome Aberrations; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics*; D009504:Neutrophils / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D016897:Respiratory Burst; D013194:Staining and Labeling
chemical_list: D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D019255:NADPH Oxidases; C527764:NCF2 protein, human