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chronic granulomatous disease

Etiology: - mutations involving a component of the NADPH oxidase system Epidemiology: 1) rare 2) prevalence is about 1 in a million Genetics: - X-linked more common than autosomal - X-linked forms - defects associated with gp91phox gene - autosomal recessive form - defects associated with NCF1 (type-1), NCF2, p21phox genes Pathology: 1) inability to generate antimicrobial oxygen metabolites 2) diminished phagocytic activity of a) neutrophils b) monocytes c) macrophages 3) phagocytes engulf organisms, but fail to develop the appropriate oxygen burst component of antimicrobial activity 4) lack of one of 4 NADPH oxidase subunits in neutrophils, monocytes, eosinophils Clinical manifestations: 1) severe infections of skin, ears, lungs, liver & bone with catalase-positive micro-organisms a) bacteria 1] Pseudomonas cepacia 2] Staphylococcus aureus 3] Chromobacterium violaceum 4] Burkholderia cepacia 5] Serratia marcescens 6] Nocardia b) fungi: Aspergillus 2) excessive inflammation with granulomas - granulomas may obstruct GI or urinary tract 3) frequent lymph node suppuration 4) gingivitis 5) aphthous ulcers 6) seborrheic dermatitis 7) generally diagnosed in childhood [2] Laboratory: - nitroblue tetrazolium (NBT) test: absent production of superoxide & H2O2 by neutrophils - see ARUP consult [5] Management: 1) long-term prophylaxis with trimethoprim-sulfamethoxazole (Bactrim) prolongs infection-free periods without increasing risk of fungal infection 2) interferon-gamma

General

cellular immune dysfunction chronic immunologic disease granulomatous disease phagocytic disorder X-linked disease

Database Correlations

OMIM correlations

References

  1. Mendelian Inheritance in Man (1990) MIM#306400
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 18. American College of Physicians, Philadelphia 1998, 2018
  3. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 334
  4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 380
  5. ARUP Consult: Chronic Granulomatous Disease - CGD The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/chronic-granulomatous-disease