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Predisposition to invasive fungal disease due to CARD9 deficiency(IMD103)

MedGen UID:
347128
Concept ID:
C1859353
Disease or Syndrome
Synonyms: Candidiasis, familial, 2; Candidiasis, familial, 2, autosomal recessive; CARD9 IMMUNODEFICIENCY; IMD103; IMMUNODEFICIENCY 103, SUSCEPTIBILITY TO FUNGAL INFECTIONS
SNOMED CT: Predisposition to invasive fungal disease due to CARD9 deficiency (1186719000); Invasive candidiasis, deep dermatophytosis syndrome (1186719000); Predisposition to invasive fungal disease due to caspase recruitment domain family member 9 deficiency (1186719000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): CARD9 (9q34.3)
 
Monarch Initiative: MONDO:0008905
OMIM®: 212050
Orphanet: ORPHA457088

Definition

A rare genetic primary immunodeficiency with characteristics of increased susceptibility to fungal infections that typically manifest as recurrent, chronic mucocutaneous candidiasis, systemic candidiasis with meningoencephalitis and deep dermatophytosis. Dermatophytes invade skin, hair, nails, lymph nodes and brain, resulting in erythematosquamous lesions, nodular subcutaneous or ulcerative infiltrations, severe onychomycosis and lymphadenopathy. [from SNOMEDCT_US]

Clinical features

From HPO
Abnormality of blood and blood-forming tissues
MedGen UID:
163092
Concept ID:
C0850715
Finding
An abnormality of the hematopoietic system.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Meningitis
MedGen UID:
6298
Concept ID:
C0025289
Disease or Syndrome
Inflammation of the meninges.
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.
Increased circulating IgE concentration
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Phaeohyphomycosis
MedGen UID:
452374
Concept ID:
C0276721
Disease or Syndrome
Phaeohyphomycosis refers to infections due to a large group of heterogenous organisms called dematiaceous or melanized fungi. These fungi are distinguished by the predominance of melanin in their cell walls, which likely acts as a virulence factor. Virtually, everyone is exposed to dematiaceous fungi through inhalation, as they are ubiquitous in the environment, although the development of infection is extremely uncommon.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Hypereosinophilia
MedGen UID:
148170
Concept ID:
C0745091
Disease or Syndrome
A severely increased count of eosinophils in the blood defined as a blood eosinophil count of at least 1.5 billion cells per liter.
Deep dermatophytosis
MedGen UID:
235599
Concept ID:
C1395264
Disease or Syndrome
A type of invasive dermatophyte infection of the deep dermis characterized by extensive dermal infiltration by fungal elements.
Abnormal natural killer cell count
MedGen UID:
866689
Concept ID:
C4021036
Finding
Any deviation from the normal overall count of natural killer (NK) cells in the circulation or a deviation from the normal distribution of NK cell subtypes.
Abnormal B cell count
MedGen UID:
866853
Concept ID:
C4021208
Finding
A deviation from the normal count of B cells, i.e., the cells that are formed in the bone marrow, migrate to the peripheral lymphatic system, and mature into plasma cells or memory cells.
Chronic oral candidiasis
MedGen UID:
870166
Concept ID:
C4024599
Disease or Syndrome
Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.
Abnormal proportion of CD8-positive T cells
MedGen UID:
1627283
Concept ID:
C4531155
Finding
Any abnormality in the proportion of CD8 T cells relative to the total number of T cells.
Abnormal proportion of CD4-positive T cells
MedGen UID:
1619121
Concept ID:
C4531156
Finding
Any abnormality in the proportion of CD4-positive T cells relative to the total number of T cells.
Chronic tinea infection
MedGen UID:
1685152
Concept ID:
C5139226
Disease or Syndrome
The term tinea means fungal infection, whereas dermatophyte refers to the fungal organisms that cause tinea. This term refers to a tinea infection that is chronic or recalcitrant to treatment and may be reflective of an immune defect.
Decreased circulating iron concentration
MedGen UID:
65918
Concept ID:
C0235988
Finding
The concentration of iron in the blood circulation is below the lower limit of normal.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPredisposition to invasive fungal disease due to CARD9 deficiency

Recent clinical studies

Etiology

Gnat S, Łagowski D, Nowakiewicz A
Mycopathologia 2021 May;186(2):163-176. Epub 2021 Feb 1 doi: 10.1007/s11046-021-00529-1. PMID: 33523393Free PMC Article
Arango-Franco CA, Moncada-Vélez M, Beltrán CP, Berrío I, Mogollón C, Restrepo A, Trujillo M, Osorio SD, Castro L, Gómez LV, Muñoz AM, Molina V, Del Río Cobaleda DY, Ruiz AC, Garcés C, Alzate JF, Cabarcas F, Orrego JC, Casanova JL, Bustamante J, Puel A, Arias AA, Franco JL
J Clin Immunol 2018 Oct;38(7):794-803. Epub 2018 Sep 28 doi: 10.1007/s10875-018-0549-0. PMID: 30264381
Pilmis B, Puel A, Lortholary O, Lanternier F
Clin Microbiol Infect 2016 Aug;22(8):681-7. Epub 2016 May 26 doi: 10.1016/j.cmi.2016.05.016. PMID: 27237547
Gavino C, Hamel N, Zeng JB, Legault C, Guiot MC, Chankowsky J, Lejtenyi D, Lemire M, Alarie I, Dufresne S, Boursiquot JN, McIntosh F, Langelier M, Behr MA, Sheppard DC, Foulkes WD, Vinh DC
J Allergy Clin Immunol 2016 Apr;137(4):1178-1188.e7. Epub 2015 Oct 29 doi: 10.1016/j.jaci.2015.09.016. PMID: 26521038

Diagnosis

Cifaldi C, Ursu GM, D'Alba I, Paccoud O, Danion F, Lanternier F, Chiriaco M
Clin Microbiol Infect 2022 Nov;28(11):1435-1440. Epub 2022 Jul 19 doi: 10.1016/j.cmi.2022.06.031. PMID: 35863627
Gnat S, Łagowski D, Nowakiewicz A
Mycopathologia 2021 May;186(2):163-176. Epub 2021 Feb 1 doi: 10.1007/s11046-021-00529-1. PMID: 33523393Free PMC Article
Corvilain E, Casanova JL, Puel A
J Clin Immunol 2018 Aug;38(6):656-693. Epub 2018 Aug 22 doi: 10.1007/s10875-018-0539-2. PMID: 30136218Free PMC Article
Pilmis B, Puel A, Lortholary O, Lanternier F
Clin Microbiol Infect 2016 Aug;22(8):681-7. Epub 2016 May 26 doi: 10.1016/j.cmi.2016.05.016. PMID: 27237547
Gavino C, Hamel N, Zeng JB, Legault C, Guiot MC, Chankowsky J, Lejtenyi D, Lemire M, Alarie I, Dufresne S, Boursiquot JN, McIntosh F, Langelier M, Behr MA, Sheppard DC, Foulkes WD, Vinh DC
J Allergy Clin Immunol 2016 Apr;137(4):1178-1188.e7. Epub 2015 Oct 29 doi: 10.1016/j.jaci.2015.09.016. PMID: 26521038

Therapy

Du B, Shen N, Hu J, Tao Y, Mo X, Cao Q
Comp Immunol Microbiol Infect Dis 2020 Jun;70:101417. Epub 2020 Jan 8 doi: 10.1016/j.cimid.2020.101417. PMID: 32113042
Gavino C, Cotter A, Lichtenstein D, Lejtenyi D, Fortin C, Legault C, Alirezaie N, Majewski J, Sheppard DC, Behr MA, Foulkes WD, Vinh DC
Clin Infect Dis 2014 Jul 1;59(1):81-4. Epub 2014 Apr 4 doi: 10.1093/cid/ciu215. PMID: 24704721Free PMC Article

Prognosis

Quan C, Li X, Shi RF, Zhao XQ, Xu H, Wang B, Wang XP, Hu WG, Cao H, Zheng J
Br J Dermatol 2019 May;180(5):1221-1225. Epub 2018 Oct 14 doi: 10.1111/bjd.17092. PMID: 30117151
Gavino C, Mellinghoff S, Cornely OA, Landekic M, Le C, Langelier M, Golizeh M, Proske S, Vinh DC
Mycoses 2018 Jan;61(1):61-65. Epub 2017 Oct 17 doi: 10.1111/myc.12701. PMID: 28984994

Clinical prediction guides

Gavino C, Mellinghoff S, Cornely OA, Landekic M, Le C, Langelier M, Golizeh M, Proske S, Vinh DC
Mycoses 2018 Jan;61(1):61-65. Epub 2017 Oct 17 doi: 10.1111/myc.12701. PMID: 28984994

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