Chronic granulomatous disease
In medicine (genetics and pediatrics) chronic granulomatous disease (CGD) is a hereditary disease where neutrophil granulocytes are unable to destroy ingested pathogens. It leads to the formation of granulomata in many organs.
Pathophysiology
Neutrophils require a set of enzymes to produce reactive oxygen species to destroy bacteria after 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 genes have 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 homozygous for the genetic defect causing glucose-6-phosphate dehydrogenase deficiency (G6PD), which is characterised by reduced NADPH levels.
Epidemiology
This rare disease occurs 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 .
