Genetic variation in chronic granulomatous disease

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Abstract

Chronic granulomatous disease dramatically illustrates the importance of individual aspects of host defenses against infection. The disease-a clinical syndrome of recurrent bacterial and fungal infections and granulomatous tissue reactions-results from a genetic defect that disables a single aspect of the microbicidal activity of phagocytic cells. That aspect is superoxide production. In normal granulocytes, the phagocytosis of a foreign particle prompts a 'respiratory burst' in which the granulocyte generates toxic derivatives of oxygen (e.g., superoxide, hydrogen peroxide, and hypochlorite). These in turn participate in creating an intracellular environment that kills ingested microorganisms. In ganulocytes of patients with chronic granulomatous disease, the phagocytosis of bacteria is normal. So is degranulation, with the release of lysosomal enzymes. However, the granulocytes fail to mount a respiratory burst. The result is recurrent infection, along with granulomas thought to be due to persistence of viable microorganisms within impaired phagocytic cells. The molecular underpinning of the respiratory burst is an oxidase system comprising a number of specific proteins that function in a coordinated way to reduce oxygen to superoxide (from which the other toxic oxygen products derive). The system's multicomponent nature might lead one to predict that defects in any of several different genes could derail the enzyme. In fact, recent studies have characterized genetic variants of chronic granulomatous disease, each caused by the absence or structural abnormality of a particular oxidase component. In the case to be presented, the patient's autosomal pattern of inheritance contrasts with that of the classic X-linked disease seen in males whose mothers are carriers. Despite this genetic heterogeneity, the failure to produce superoxide and related oxygen derivatives is found in all patients, and clinical features are similar.

Original languageEnglish (US)
Pages (from-to)51-55+59+63+69
JournalHospital Practice
Volume25
Issue number5 A
StatePublished - Jan 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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