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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. more...

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Medicines

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.

Read more at Wikipedia.org


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Severe chronic laryngitis mimicking a granulomatous disease
From Ear, Nose & Throat Journal, 11/1/04 by Mary Es Beaver

A 48-year-old woman presented with chronic cough and hoarseness that had become progressively worse over the preceding 6 months. Her history was significant for cigarette smoking (50 pack-yr) and moderate alcohol use (3 highballs/day). A previous microlaryngoscopy with biopsy had detected chronic inflammation and mild dysplasia of the vocal folds.

A granulomatous or autoimmune process was suspected based on findings of stroboscopy (figure). Findings on laboratory evaluations--including measurements of c- and p-antineutrophil cytoplasmic antibody (c-ANCA and p-ANCA), angiotensin-converting enzyme (ACE), antinuclear antibody (ANA), erythrocyte sedimentation rate (ESR), sputum acid-fast bacilli (AFB), and a complete blood count--were normal. The immunoglobulin E (IgE) level was mildly elevated at 233 U/ml. Findings on chest radiograph and pulmonary function testing were normal.

[FIGURE OMITTED]

A pulmonary consultation was obtained, and smoking cessation measures were begun. The patient was aggressively treated for laryngopharyngeal reflux and allergy with esomeprazole, nizatidine, montelukast sodium, and fluticasone. She was scheduled for repeat microlaryngoscopy and biopsy for tissue diagnosis.

Three months later, she returned for a preoperative visit. Her laryngeal exam showed dramatic improvement, and surgery was cancelled. She continues to struggle with smoking and alcohol cessation.

From the Anderson Center for Voice and Swallowing, Houston (Dr. Beaver), and the Texas Voice Center, Houston (Dr. Stasney and Dr. Rodriguez).

COPYRIGHT 2004 Medquest Communications, LLC
COPYRIGHT 2005 Gale Group

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