- Joint Pain
- Weight loss
- Discoid lupus-like disease
- Photosensitive rashes
CGD is a disorder that affects phagocyte function and that is caused by mutations in any 1 of 5 subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system.1 There are 2 major types of CGD: X-linked and autosomal recessive.1
Males who inherit the mutation will be affected, while females who inherit the mutation will be carriers and may also be at risk as autoimmune events are more common in female CGD carriers than in healthy individuals.1-3
Autosomal recessive CGD can be passed down when both parents have a gene mutation. Each child has a 25% chance of being affected, 50% chance of being an asymptomatic carrier, and 25% chance of being unaffected and not a carrier.1
Symptomatic mothers of sons with X-linked CGD should be monitored as potential patients as they may present with signs of CGD and experience a wide range of inflammatory and autoimmune symptoms such as3-7:
A 2018 study found that 48% of X-linked carriers reported infections, autoimmune symptoms, or both.3 As a result, X-linked carriers of CGD may be at risk of serious infection, should be evaluated, routinely tested, and monitored as patients, especially as they age.
CGD is most commonly inherited in an X-linked mode, with the subunit gp91phox of NADPH oxidase being affected; all other CGD-related subunit deficiencies are inherited in an autosomal recessive mode.1,4,8 CGD can also arise from a de novo mutation.1,8 The vast majority of patients with autosomal recessive CGD have p47phox deficiency.1,4,8
Because of the differences in subunit deficiencies and inheritance of CGD, there is heterogeneity in disease onset and severity.1,4,8
*Serious infection was defined as a clinical event requiring hospitalization and intravenous antibiotics.
|Subunit (Gene)||Mode of Inheritence||Frequency||Sex Affected|
|gp91 phox (CYBB)||X linked||65-70% 1,4,8||Male/rare in females|
|p47 phox (NCF1)||Autosomal recessive||20-25% 1,4,8||Male/female|
|p67 phox (NCF2)||Autosomal recessive||5-6% 1,4,8||Male/female|
|p22 phox (CYBA)||Autosomal recessive||3-6% 1,4,8||Male/female|
|p40 phox (NCF4)||Autosomal recessive||25 cases 1,9,10|
|Subunit (Gene): gp91 phox (CYBB)||Mode of Inheritence: X linked||Frequency: 65-70% 1,4,8||Sex Affected: Male/rare in females|
|Subunit (Gene): p47 phox (NCF1)||Mode of Inheritence: Autosomal recessive||Frequency: 20-25% 1,4,8||Sex Affected: Male/female|
|Subunit (Gene): p67 phox (NCF2)||Mode of Inheritence: Autosomal recessive||Frequency: 5-6% 1,4,8||Sex Affected: Male/female|
|Subunit (Gene): p22 phox (CYBA)||Mode of Inheritence: Autosomal recessive||Frequency: 3-6% 1,4,8||Sex Affected: Male/female|
|Subunit (Gene): p40 phox (NCF4)||Mode of Inheritence: Autosomal recessive||Frequency: 25 cases 1,9,10|
The data in the above table is from the 1980s and 1990s, which may not fully reflect current distributions based on improved diagnostic tests.
References: 1. Leiding JW, Holland SM. Chronic granulomatous disease. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews® Seattle (WA): University of Washington, Seattle; 1993-2022. 2. Rider NL, Jameson MB, Creech CB. Chronic granulomatous disease: epidemiology, pathophysiology, and genetic basis of disease. J Pediatric Infect Dis Soc. 2018;7(suppl 1):S2-S5. 3. Marciano BE, Zerbe CS, Falcone EL, et al. X-linked carriers of chronic granulomatous disease: Illness, lyonization, and stability. J Allergy Clin Immunol. 2018;141(1):365-371. 4. Holland SM. Chronic granulomatous disease. Clin Rev Allergy Immunol. 2010;38(1):3-10. 5. Battersby AC, Bruggins H, Pearce MS, et al. Inflammatory and autoimmune manifestations in X-linked carriers of chronic granulomatous disease in the United Kingdom. J Allergy Clin Immunol. 2017;140(2):628-630.e6. 6. Magnani A, Brosselin P, Beauté J, et al. Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease. J Allergy Clin Immunol. 2014;134(3):655-662.e8. 7. Song E, Jaishankar GB, Saleh H, Jithpratuck W, Sahni R, Krishnaswamy G. Chronic granulomatous disease: a review of the infectious and inflammatory complications. Clin Mol Allergy. 2011;9(1):10-24. 8. Kuhns DB, Alvord WG, Heller T, et al. Residual NADPH oxidase and survival in chronic granulomatous disease. N Engl J Med. 2010;363(27):2600-2610. 9. Matute JD, Arias AA, Wright NA, et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40phox and selective defects in neutrophil NADPH oxidase activity. Blood. 2009;114(15):3309-3315. 10. van de Geer A, Nieto-Patlán A, Kuhns DB, et al. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest. 2018;128(9):3957-3975.
ACTIMMUNE® (Interferon gamma-1b) is indicated:
ACTIMMUNE® (Interferon gamma-1b) is indicated: