Chronic granulomatous disease caused by a deficiency in p47(phox) mimicking Crohn's disease.
We describe 2 cases of autosomal recessive chronic granulomatous disease (CGD) in 2 sisters presenting with a picture consistent with inflammatory bowel disease. The index case is a 10-year-old girl with a history of refractory Crohn's colitis treated with aggressive immunosuppressive therapy whose course subsequently was complicated by central nervous system aspergillosis. Additional evaluation showed a diagnosis of CGD, an underlying immunodeficiency in which phagocytes fail to produce microbicidal reactive oxygen intermediates because of inherited defects in the reduced form of nicotinamide-adenine phosphate dinucleotide (NADPH) oxidase. The diagnosis of a typically X-linked inherited disease in our female patient suggested that she had 1 of the 3 less common autosomal recessive forms of the disease. This was confirmed by studies showing the absence of the p47(phox) subunit of NADPH oxidase in her neutrophils and the presence of a homozygous dinucleotide deletion in the neutrophil cytosolic factor 1 gene that encodes p47(phox). Additional analyses of members of the patient's immediate family showed the same homozygous mutation in 2 siblings, 1 of whom also developed chronic colitis consistent with a diagnosis of Crohn's disease. These 2 cases emphasize the importance of high clinical suspicion for an alternative diagnosis of immune deficiency in the setting of presumed inflammatory bowel disease and opportunistic infection.
Huang
Jeannie S
JS
Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California, San Diego 92103-8450, USA. jshuang@ucsd.edu
Noack
Deborah
D
Rae
Julie
J
Ellis
Beverly A
BA
Newbury
Robert
R
Pong
Alice L
AL
Lavine
Joel E
JE
Curnutte
John T
JT
Bastian
John
J
D000293:Adolescent; D002648:Child; D003424:Crohn Disease / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D020022:Genetic Predisposition to Disease; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007410:Intestinal Diseases / Q000209:etiology; D009154:Mutation; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000378:metabolism*
D010750:Phosphoproteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1