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Severe combined immunodeficiency due to LCK deficiency(IMD22)

MedGen UID:
862670
Concept ID:
C4014233
Disease or Syndrome
Synonym: Immunodeficiency 22
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): LCK (1p35.2)
 
Monarch Initiative: MONDO:0014334
OMIM®: 615758
Orphanet: ORPHA280142

Definition

Immunodeficiency-22 (IMD22) is an autosomal recessive disorder characterized by the onset of recurrent bacterial, viral, and fungal respiratory, gastrointestinal, and skin infections in infancy or early childhood. Immunologic workup shows severe T-cell lymphopenia, particularly affecting the CD4+ subset, and impaired proximal TCR intracellular signaling and activation. Although NK cells and B cells are normal, some patients may have hypogammaglobulinemia secondary to the T-cell defect. There are variable manifestations, likely due to the severity of the particular LCK mutation: patients may develop prominent skin lesions resembling epidermodysplasia verruciformis, gastrointestinal inflammation, and virus-induced malignancy. The disease can be fatal in childhood, but hematopoietic stem cell transplant (HSCT) may be curative (Hauck et al., 2012; Li et al., 2016; Keller et al., 2023). [from OMIM]

Clinical features

From HPO
Capillary leak
MedGen UID:
730470
Concept ID:
C1382398
Finding
An acute phenomenon characterized by hypotension and anasarca due to the loss of plasma volume into peripheral tissues, with evidence of decreased plasma volume (hemoconcentration) and protein loss from the intravascular space (hypoalbuminemia) during acute episodes.
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.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Protracted diarrhea
MedGen UID:
141631
Concept ID:
C0473133
Disease or Syndrome
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Abscess
MedGen UID:
1684
Concept ID:
C0000833
Disease or Syndrome
An abscess is a localized collection of purulent material surrounded by inflammation and granulation.
Autoimmunity
MedGen UID:
2136
Concept ID:
C0004368
Pathologic Function
The occurrence of an immune reaction against the organism's own cells or tissues.
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.
Panniculitis
MedGen UID:
45301
Concept ID:
C0030326
Disease or Syndrome
Inflammation of subcutaneous adipose tissue.
Pericarditis
MedGen UID:
18377
Concept ID:
C0031046
Disease or Syndrome
Inflammation of the sac-like covering around the heart (pericardium).
Decreased circulating IgA concentration
MedGen UID:
57934
Concept ID:
C0162538
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Decreased circulating IgE concentration
MedGen UID:
1714318
Concept ID:
C0853668
Finding
An abnormally decreased level of immunoglobulin E (IgE) in blood.
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 IgG concentration
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Decreased proportion of CD4-positive helper T cells
MedGen UID:
1719772
Concept ID:
C5235140
Finding
A decreased proportion of circulating CD4-positive helper T cells relative to total T cell count.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Retinal vasculitis
MedGen UID:
57503
Concept ID:
C0152026
Disease or Syndrome
Inflammation of retinal blood vessels as manifested by perivascular sheathing or cuffing, vascular leakage and/or occlusion.

Term Hierarchy

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

Recent clinical studies

Etiology

Racioppi L, Cancrini C, Romiti ML, Angelini F, Di Cesare S, Bertini E, Livadiotti S, Gambarara MG, Matarese G, Lago Paz F, Stefanini M, Rossi P
Clin Exp Immunol 2001 Dec;126(3):511-8. doi: 10.1046/j.1365-2249.2001.01625.x. PMID: 11737070Free PMC Article

Therapy

Ha TC, Morgan MA, Thrasher AJ, Schambach A
Hum Gene Ther 2024 Sep;35(17-18):669-679. Epub 2024 Aug 27 doi: 10.1089/hum.2024.103. PMID: 39150017