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.
Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California, San Diego 92103-8450, USA. jshuang@ucsd.edu
Jeannie S
JS
Huang
Deborah
D
Noack
Julie
J
Rae
Beverly A
BA
Ellis
Robert
R
Newbury
Alice L
AL
Pong
Joel E
JE
Lavine
John T
JT
Curnutte
John
J
Bastian
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