Chronic granulomatous disease

In medicine(geneticsand pediatrics) chronic granulomatous disease (CGD) is a hereditary diseasewhere neutrophil granulocytesare unable to destroy ingested pathogens. It leads to the formation of granulomatain many organs.

Pathophysiology

Neutrophilsrequire a set of enzymesto produce reactive oxygen speciesto destroy bacteriaafter their phagocytosis. Together these enzymes are termed "phagocyte NADPH oxidase" (phox). Defects in one of these enzymes can all cause CGD of varying severity, dependent on the defect. There are over 410 known defects in the enzyme complex.

Genetics

Four geneshave been implicated in CGD (p is the weight of the protein in kDa; the g means glycoprotein):

• CYBB, coding the gp91-phox subunit (X-linked, accounts for 2/3 of the cases);
• CYBA, coding p22-phox
• NCF-1, coding p47-phox
• NCF-2, coding p67-phox
• A fifth gene, coding for p40-phox, has not been implicated

A low level of NADPH, the cofactor required for superoxide synthesis, can lead to CGD. This has been reported in women who are homozygousfor the genetic defect causing glucose-6-phosphate dehydrogenase deficiency(G6PD), which is characterised by reduced NADPH levels.

Epidemiology

This rare diseaseoccurs in about 1 on 200,000 - 250,000 live births.

References

• Heyworth PG, Cross AR, Curnutte JT. Chronic granulomatous disease. Curr Opin Immunol 2003;15:578?584. DOI 10.1016/S0952-7915(03)00109-2.

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It uses material from the http://en.wikipedia.org/wiki/Chronic+granulomatous+disease Wikipedia article Chronic granulomatous disease.