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Granulomatous disease, chronic, autosomal recessive, 5(CGD5)

MedGen UID:
1710326
Concept ID:
C5394542
Disease or Syndrome
Synonym: GRANULOMATOUS DISEASE, CHRONIC, DUE TO CYBC1 DEFICIENCY
 
Gene (location): CYBC1 (17q25.3)
 
Monarch Initiative: MONDO:0030066
OMIM®: 618935

Disease characteristics

Excerpted from the GeneReview: Chronic Granulomatous Disease
Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes (neutrophils, monocytes, macrophages, and eosinophils) resulting from impaired killing of bacteria and fungi. CGD is characterized by severe recurrent bacterial and fungal infections and dysregulated inflammatory responses resulting in granuloma formation and other inflammatory disorders such as colitis. Infections typically involve the lung (pneumonia), lymph nodes (lymphadenitis), liver (abscess), bone (osteomyelitis), and skin (abscesses or cellulitis). Granulomas typically involve the genitourinary system (bladder) and gastrointestinal tract (often the pylorus initially, and later the esophagus, jejunum, ileum, cecum, rectum, and perirectal area). Some males with X-linked CGD have McLeod neuroacanthocytosis syndrome as the result of a contiguous gene deletion. While CGD may present anytime from infancy to late adulthood, the vast majority of affected individuals are diagnosed before age five years. Use of antimicrobial prophylaxis and therapy has greatly improved overall survival. [from GeneReviews]
Authors:
Jennifer W Leiding  |  Steven M Holland   view full author information

Additional description

From OMIM
Autosomal recessive chronic granulomatous disease-5 (CGD5) is a primary immunodeficiency characterized by onset of recurrent infections and severe colitis in the first decade of life. Patients often present with features of inflammatory bowel disease and may show granulomata on biopsy. Patients are particularly susceptible to catalase-positive organisms, including Burkholderia cepacia, Legionella, and Candida albicans. Some patients may develop autoinflammatory symptoms, including recurrent fever in the absence of infection, hemolytic anemia, and lymphopenia. Additional features may include short stature, viral infections, cutaneous abscesses, pulmonary infections, and lymphadenitis. Hematopoietic bone marrow transplant is curative. The disorder results from impaired oxidative burst via the NAPDH oxidative complex in macrophages and neutrophils (summary by Arnadottir et al., 2018 and Thomas et al., 2019). For a discussion of genetic heterogeneity of CGD, see the X-linked form (CGDX; 306400).  http://www.omim.org/entry/618935

Clinical features

From HPO
Nephrotic syndrome
MedGen UID:
10308
Concept ID:
C0027726
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Ulcerative colitis
MedGen UID:
3532
Concept ID:
C0009324
Disease or Syndrome
A chronic inflammatory bowel disease that includes characteristic ulcers, or open sores, in the colon. The main symptom of active disease is usually constant diarrhea mixed with blood, of gradual onset and intermittent periods of exacerbated symptoms contrasting with periods that are relatively symptom-free. In contrast to Crohn's disease this special form of colitis begins in the distal parts of the rectum, spreads continually upwards and affects only mucose and submucose tissue of the colon.
Crohn disease
MedGen UID:
3664
Concept ID:
C0010346
Disease or Syndrome
A chronic granulomatous inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea which may be bloody, vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation.
Anal fissure
MedGen UID:
42031
Concept ID:
C0016167
Acquired Abnormality
A small tear in the thin, moist tissue (mucosa) that lines the anus. It appears as a crack or slit in the mucous membrane of the anus.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Perianal abscess
MedGen UID:
14677
Concept ID:
C0031019
Disease or Syndrome
The presence of an abscess located around the anus.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Pleural effusion
MedGen UID:
10805
Concept ID:
C0032227
Disease or Syndrome
The presence of an excessive amount of fluid in the pleural cavity.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Abscess
MedGen UID:
1684
Concept ID:
C0000833
Disease or Syndrome
An inflammatory process characterized by the accumulation of pus within a newly formed tissue cavity which is the result of a bacterial, fungal, or parasitic infection or the presence of a foreign body.
Acute pancreatitis
MedGen UID:
7872
Concept ID:
C0001339
Disease or Syndrome
A acute form of pancreatitis.
Eczema
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Granuloma
MedGen UID:
5376
Concept ID:
C0018188
Pathologic Function
A compact, organized collection of mature mononuclear phagocytes, which may be but is not necessarily accompanied by accessory features such as necrosis.
Lymphadenitis
MedGen UID:
7410
Concept ID:
C0024205
Disease or Syndrome
Inflammation of a lymph node.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Onychomycosis
MedGen UID:
11825
Concept ID:
C0040261
Disease or Syndrome
A fungal infection of the toenails or fingernails that tends to cause the nails to thicken, discolor, disfigure, and split.
Rheumatoid factor positive
MedGen UID:
56226
Concept ID:
C0151379
Laboratory or Test Result
The presence in the serum of an autoantibody directed against the Fc portion of IgG.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargment (swelling) of a lymph node.
Recurrent tonsillitis
MedGen UID:
1781351
Concept ID:
C0740402
Disease or Syndrome
Inflammation of the tonsils that has occurred repeatedly. The definition of recurrent may vary somewhat, but the criteria used recently as a measure of severity were five or more episodes of true tonsillitis per year, symptoms recurring for at least a year, and episodes that are disabling and that prevent normal functioning. In some cases recurrent tonsillitis may be related to immunosusceptibility. Evidence exists for a genetic predisposition for recurrent tonsillitis.
Impaired oxidative burst
MedGen UID:
898272
Concept ID:
C4280805
Laboratory or Test Result
In the NBT test, neutrophils change the colorless compound NBT into a compound with a deep blue color. If this test is negative (i.e., no blue color is produced), then this indicates a defect in superoxide-generating NADPH oxidase activity with inability to efficiently kill phagocytized bacteria.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.

Recent clinical studies

Etiology

Vignesh P, Loganathan SK, Sudhakar M, Chaudhary H, Rawat A, Sharma M, Shekar A, Vaiphei K, Kumar N, Singh Sachdeva MU, Jindal AK, Suri D, Gupta A, Ray P, Imai K, Ohara O, Nonoyama S, Lau YL, Singh S
J Allergy Clin Immunol Pract 2021 Feb;9(2):771-782.e3. Epub 2020 Nov 28 doi: 10.1016/j.jaip.2020.11.041. PMID: 33259975
Yanagimachi M, Kato K, Iguchi A, Sasaki K, Kiyotani C, Koh K, Koike T, Sano H, Shigemura T, Muramatsu H, Okada K, Inoue M, Tabuchi K, Nishimura T, Mizukami T, Nunoi H, Imai K, Kobayashi M, Morio T
Front Immunol 2020;11:1617. Epub 2020 Jul 29 doi: 10.3389/fimmu.2020.01617. PMID: 32849547Free PMC Article
Gao LW, Yin QQ, Tong YJ, Gui JG, Liu XY, Feng XL, Yin J, Liu J, Guo Y, Yao Y, Xu BP, He JX, Shen KL, Lau YL, Jiang ZF
Pediatr Allergy Immunol 2019 May;30(3):378-386. Epub 2019 Mar 27 doi: 10.1111/pai.13033. PMID: 30716179Free PMC Article
Bortoletto P, Lyman K, Camacho A, Fricchione M, Khanolkar A, Katz BZ
Pediatr Infect Dis J 2015 Oct;34(10):1110-4. doi: 10.1097/INF.0000000000000840. PMID: 26181896Free PMC Article
Meshaal S, El Hawary R, Abd Elaziz D, Alkady R, Galal N, Boutros J, Elmarsafy A
Allergol Immunopathol (Madr) 2015 May-Jun;43(3):279-85. Epub 2015 Mar 19 doi: 10.1016/j.aller.2014.11.003. PMID: 25796307

Diagnosis

Lin TS, Lee JH, Wang LC, Yang YH, Lau YL, Lee WI, Lin YT, Chiang BL, Yu HH
J Microbiol Immunol Infect 2023 Feb;56(1):130-138. Epub 2022 Jul 6 doi: 10.1016/j.jmii.2022.06.005. PMID: 35842407
Vignesh P, Loganathan SK, Sudhakar M, Chaudhary H, Rawat A, Sharma M, Shekar A, Vaiphei K, Kumar N, Singh Sachdeva MU, Jindal AK, Suri D, Gupta A, Ray P, Imai K, Ohara O, Nonoyama S, Lau YL, Singh S
J Allergy Clin Immunol Pract 2021 Feb;9(2):771-782.e3. Epub 2020 Nov 28 doi: 10.1016/j.jaip.2020.11.041. PMID: 33259975
Yanagimachi M, Kato K, Iguchi A, Sasaki K, Kiyotani C, Koh K, Koike T, Sano H, Shigemura T, Muramatsu H, Okada K, Inoue M, Tabuchi K, Nishimura T, Mizukami T, Nunoi H, Imai K, Kobayashi M, Morio T
Front Immunol 2020;11:1617. Epub 2020 Jul 29 doi: 10.3389/fimmu.2020.01617. PMID: 32849547Free PMC Article
Sanabria D, Giménez V, Martínez de Cuéllar C, Carpinelli M, Benegas S, Insaurralde S
Rev Chil Pediatr 2020 Feb;91(1):19-26. Epub 2020 Jan 22 doi: 10.32641/rchped.v91i1.986. PMID: 32730409
Kutluğ Ş, Şensoy G, Birinci A, Saraymen B, Yavuz Köker M, Yιldιran A
Asian Pac J Allergy Immunol 2018 Mar;36(1):35-41. doi: 10.12932/AP0859. PMID: 28577521

Therapy

Si Y, Dou Y, Zhai X, Zhou C, Lu W, Meng Y, Qian X, Chen J, Wang P, Luo C, Yu J, Tang X
Clin Immunol 2024 Mar;260:109919. Epub 2024 Feb 2 doi: 10.1016/j.clim.2024.109919. PMID: 38309448
Lin TS, Lee JH, Wang LC, Yang YH, Lau YL, Lee WI, Lin YT, Chiang BL, Yu HH
J Microbiol Immunol Infect 2023 Feb;56(1):130-138. Epub 2022 Jul 6 doi: 10.1016/j.jmii.2022.06.005. PMID: 35842407
Yanagimachi M, Kato K, Iguchi A, Sasaki K, Kiyotani C, Koh K, Koike T, Sano H, Shigemura T, Muramatsu H, Okada K, Inoue M, Tabuchi K, Nishimura T, Mizukami T, Nunoi H, Imai K, Kobayashi M, Morio T
Front Immunol 2020;11:1617. Epub 2020 Jul 29 doi: 10.3389/fimmu.2020.01617. PMID: 32849547Free PMC Article
Gao LW, Yin QQ, Tong YJ, Gui JG, Liu XY, Feng XL, Yin J, Liu J, Guo Y, Yao Y, Xu BP, He JX, Shen KL, Lau YL, Jiang ZF
Pediatr Allergy Immunol 2019 May;30(3):378-386. Epub 2019 Mar 27 doi: 10.1111/pai.13033. PMID: 30716179Free PMC Article
Rawat A, Vignesh P, Sharma A, Shandilya JK, Sharma M, Suri D, Gupta A, Gautam V, Ray P, Rudramurthy SM, Chakrabarti A, Imai K, Nonoyama S, Ohara O, Lau YL, Singh S
J Clin Immunol 2017 Apr;37(3):319-328. Epub 2017 Mar 22 doi: 10.1007/s10875-017-0382-x. PMID: 28332028

Prognosis

Mellouli F, Ksouri H, Lajhouri M, Ben Khaled M, Rekaya S, Ben Fraj E, Ouederni M, Barbouche MR, Bejaoui M
Clin Pediatr (Phila) 2022 Oct;61(9):629-644. Epub 2022 Jun 8 doi: 10.1177/00099228221096329. PMID: 35678026
Neehus AL, Tuano K, Le Voyer T, Nandiwada SL, Murthy K, Puel A, Casanova JL, Chinen J, Bustamante J
J Clin Immunol 2022 Aug;42(6):1244-1253. Epub 2022 May 18 doi: 10.1007/s10875-022-01268-8. PMID: 35585372Free PMC Article
Yanagimachi M, Kato K, Iguchi A, Sasaki K, Kiyotani C, Koh K, Koike T, Sano H, Shigemura T, Muramatsu H, Okada K, Inoue M, Tabuchi K, Nishimura T, Mizukami T, Nunoi H, Imai K, Kobayashi M, Morio T
Front Immunol 2020;11:1617. Epub 2020 Jul 29 doi: 10.3389/fimmu.2020.01617. PMID: 32849547Free PMC Article
Köker MY, Camcıoğlu Y, van Leeuwen K, Kılıç SŞ, Barlan I, Yılmaz M, Metin A, de Boer M, Avcılar H, Patıroğlu T, Yıldıran A, Yeğin O, Tezcan I, Sanal Ö, Roos D
J Allergy Clin Immunol 2013 Nov;132(5):1156-1163.e5. Epub 2013 Jul 31 doi: 10.1016/j.jaci.2013.05.039. PMID: 23910690
Ahlin A, De Boer M, Roos D, Leusen J, Smith CI, Sundin U, Rabbani H, Palmblad J, Elinder G
Acta Paediatr 1995 Dec;84(12):1386-94. doi: 10.1111/j.1651-2227.1995.tb13575.x. PMID: 8645957

Clinical prediction guides

Mellouli F, Ksouri H, Lajhouri M, Ben Khaled M, Rekaya S, Ben Fraj E, Ouederni M, Barbouche MR, Bejaoui M
Clin Pediatr (Phila) 2022 Oct;61(9):629-644. Epub 2022 Jun 8 doi: 10.1177/00099228221096329. PMID: 35678026
Neehus AL, Tuano K, Le Voyer T, Nandiwada SL, Murthy K, Puel A, Casanova JL, Chinen J, Bustamante J
J Clin Immunol 2022 Aug;42(6):1244-1253. Epub 2022 May 18 doi: 10.1007/s10875-022-01268-8. PMID: 35585372Free PMC Article
Sanabria D, Giménez V, Martínez de Cuéllar C, Carpinelli M, Benegas S, Insaurralde S
Rev Chil Pediatr 2020 Feb;91(1):19-26. Epub 2020 Jan 22 doi: 10.32641/rchped.v91i1.986. PMID: 32730409
Kutluğ Ş, Şensoy G, Birinci A, Saraymen B, Yavuz Köker M, Yιldιran A
Asian Pac J Allergy Immunol 2018 Mar;36(1):35-41. doi: 10.12932/AP0859. PMID: 28577521
Ahlin A, De Boer M, Roos D, Leusen J, Smith CI, Sundin U, Rabbani H, Palmblad J, Elinder G
Acta Paediatr 1995 Dec;84(12):1386-94. doi: 10.1111/j.1651-2227.1995.tb13575.x. PMID: 8645957

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