Focus on FOCIS: The continuing diagnostic challenge of autosomal recessive chronic granulomatous disease

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2008-08, Vol.128 (2), p.117-126
• Main Authors: Yu, Grace, Hong, David K, Dionis, Kira Y, Rae, Julie, Heyworth, Paul G, Curnutte, John T, Lewis, David B
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Biological and medical sciences; Burkholderia cepacia; Burkholderia Infections - complications; Case Report; Child; Chromosome Aberrations; Chronic granulomatous disease; Dihydrorhodamine; Federation of Clinical Immunology Societies; Female; Flow cytometry; FOCIS Centers of Excellence; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Recessive; Genotype; Granulomatous Disease, Chronic - complications; Granulomatous Disease, Chronic - diagnosis; Granulomatous Disease, Chronic - genetics; Hematologic and hematopoietic diseases; Homozygote; Humans; Hypomorphic mutation; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Medical sciences; Mutation; NADPH Oxidases - genetics; NCF-2 gene; Neutrophils - metabolism; Other diseases. Hematologic involvement in other diseases; p67 phagocyte oxidase; Phosphoproteins - genetics; Phosphoproteins - metabolism; Respiratory Burst; Staining and Labeling
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2008.05.008

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.