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Severe combined immunodeficiency due to IKK2 deficiency(IMD15B)

MedGen UID:
1648569
Concept ID:
C4747743
Disease or Syndrome
Synonyms: Immunodeficiency 15; IMMUNODEFICIENCY 15B
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): IKBKB (8p11.21)
 
Monarch Initiative: MONDO:0014267
OMIM®: 615592
Orphanet: ORPHA397787

Definition

Immunodeficiency-15B (IMD15B) is an autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T cells. However, functional studies show impaired differentiation and activation of immune cells (summary by Pannicke et al., 2013). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Agammaglobulinemia
MedGen UID:
168
Concept ID:
C0001768
Disease or Syndrome
A lasting absence of total IgG and total IgA and total IgM in the blood circulation, whereby at most trace quantities can be measured.
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.
Monocytosis
MedGen UID:
39091
Concept ID:
C0085702
Disease or Syndrome
An increased number of circulating monocytes.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Reduced natural killer cell count
MedGen UID:
383765
Concept ID:
C1855767
Finding
Less than normal number of natural killer cells, a type of lymphocyte in the innate immune system with an ability to mediate cytotoxicity and produce cytokines after the ligation of a germline-encoded activation receptor.
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.
Decreased circulating antibody concentration
MedGen UID:
892481
Concept ID:
C4048270
Finding
An abnormally decreased level of immunoglobulin in blood.
Decreased lymphocyte proliferation in response to mitogen
MedGen UID:
1615224
Concept ID:
C4531166
Cell or Molecular Dysfunction
A decreased proliferative response of lymphocytes in vitro or in vivo, when stimulated with mitogens, such as phytohemagglutinin (PHA).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSevere combined immunodeficiency due to IKK2 deficiency

Recent clinical studies

Etiology

Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M, Janda A, Hese K, Schlesier M, Holzmann K, Borte S, Laux C, Rump EM, Rosenberg A, Zelinski T, Schrezenmeier H, Wirth T, Ehl S, Schroeder ML, Schwarz K
N Engl J Med 2013 Dec 26;369(26):2504-14. doi: 10.1056/NEJMoa1309199. PMID: 24369075

Prognosis

Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M, Janda A, Hese K, Schlesier M, Holzmann K, Borte S, Laux C, Rump EM, Rosenberg A, Zelinski T, Schrezenmeier H, Wirth T, Ehl S, Schroeder ML, Schwarz K
N Engl J Med 2013 Dec 26;369(26):2504-14. doi: 10.1056/NEJMoa1309199. PMID: 24369075

Clinical prediction guides

Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M, Janda A, Hese K, Schlesier M, Holzmann K, Borte S, Laux C, Rump EM, Rosenberg A, Zelinski T, Schrezenmeier H, Wirth T, Ehl S, Schroeder ML, Schwarz K
N Engl J Med 2013 Dec 26;369(26):2504-14. doi: 10.1056/NEJMoa1309199. PMID: 24369075

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