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Immunodeficiency 63 with lymphoproliferation and autoimmunity(IMD63)

MedGen UID:
1682943
Concept ID:
C5193126
Disease or Syndrome
Synonyms: CD122 DEFICIENCY; IL2RB DEFICIENCY; INTERLEUKIN 2 RECEPTOR, BETA, DEFICIENCY OF
 
Gene (location): IL2RB (22q12.3)
 
Monarch Initiative: MONDO:0032782
OMIM®: 618495

Definition

Immunodeficiency-63 with lymphoproliferation and autoimmunity (IMD63) is an autosomal recessive disorder characterized by immune dysregulation. Affected individuals present in infancy with features of both abnormal activation of certain immune signaling pathways, resulting in lymphoid proliferation, dermatitis, enteropathy, and hypergammaglobulinemia, as well as features of immunodeficiency, such as recurrent infections and increased susceptibility to viral infections, especially CMV. Laboratory studies show increased NK cells that show impaired differentiation, as well as abnormal T cell populations or responses. Some patients may die in childhood; hematopoietic bone marrow transplantation is curative (summary by Zhang et al., 2019). [from OMIM]

Clinical features

From HPO
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
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.
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.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Lymphoid interstitial pneumonia
MedGen UID:
82682
Concept ID:
C0264511
Disease or Syndrome
Lymphocytic interstitial pneumonitis is a benign lymphoproliferative disorder of the lung that is characterized by the presence of a dense, predominantly lymphocytic interstitial infiltrate (lymphocytes, plasma cells, other elements of the lymphoreticular system) that expands the alveolar septa.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
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.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargement (swelling) of a lymph node.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Decreased CD4:CD8 ratio
MedGen UID:
163125
Concept ID:
C0853905
Finding
An abnormal reduction of the relative proportion of CD4+ to CD8+ T cells.
Increased circulating IgG concentration
MedGen UID:
347032
Concept ID:
C1858977
Finding
An abnormally increased level of immunoglobulin G in blood.
Persistent CMV viremia
MedGen UID:
1696514
Concept ID:
C5139221
Finding
Lasting (uncontrolled) presence of cytomegalovirus in the blood circulation.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.

Recent clinical studies

Etiology

Segura-Tudela A, López-Nevado M, Nieto-López C, García-Jiménez S, Díaz-Madroñero MJ, Delgado Á, Cabrera-Marante O, Pleguezuelo D, Morales P, Paz-Artal E, Gil-Niño J, Marco FM, Serrano C, González-Granado LI, Quesada-Espinosa JF, Allende LM
J Clin Immunol 2024 Feb 16;44(3):61. doi: 10.1007/s10875-024-01664-2. PMID: 38363452Free PMC Article
Hanson J, Bonnen PE
Clin Exp Med 2024 Jan 27;24(1):17. doi: 10.1007/s10238-023-01259-y. PMID: 38280023Free PMC Article
Mormile I, Punziano A, Riolo CA, Granata F, Williams M, de Paulis A, Spadaro G, Rossi FW
Front Immunol 2021;12:652487. Epub 2021 Jul 5 doi: 10.3389/fimmu.2021.652487. PMID: 34290696Free PMC Article
Azizi G, Bagheri Y, Tavakol M, Askarimoghaddam F, Porrostami K, Rafiemanesh H, Yazdani R, Kiaee F, Habibi S, Abouhamzeh K, Mohammadi H, Qorbani M, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2018;18(5):537-545. doi: 10.2174/1871530318666180413110216. PMID: 29651973

Diagnosis

Segura-Tudela A, López-Nevado M, Nieto-López C, García-Jiménez S, Díaz-Madroñero MJ, Delgado Á, Cabrera-Marante O, Pleguezuelo D, Morales P, Paz-Artal E, Gil-Niño J, Marco FM, Serrano C, González-Granado LI, Quesada-Espinosa JF, Allende LM
J Clin Immunol 2024 Feb 16;44(3):61. doi: 10.1007/s10875-024-01664-2. PMID: 38363452Free PMC Article
Hanson J, Bonnen PE
Clin Exp Med 2024 Jan 27;24(1):17. doi: 10.1007/s10238-023-01259-y. PMID: 38280023Free PMC Article
Fetyan S, Sakrani NF, Yassin F, Abdallah MF, Elzein N, Azizi G, ElGhazali G
Iran J Allergy Asthma Immunol 2022 Apr 11;21(2):219-227. doi: 10.18502/ijaai.v21i2.9230. PMID: 35490276
Mormile I, Punziano A, Riolo CA, Granata F, Williams M, de Paulis A, Spadaro G, Rossi FW
Front Immunol 2021;12:652487. Epub 2021 Jul 5 doi: 10.3389/fimmu.2021.652487. PMID: 34290696Free PMC Article
Azizi G, Bagheri Y, Tavakol M, Askarimoghaddam F, Porrostami K, Rafiemanesh H, Yazdani R, Kiaee F, Habibi S, Abouhamzeh K, Mohammadi H, Qorbani M, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2018;18(5):537-545. doi: 10.2174/1871530318666180413110216. PMID: 29651973

Prognosis

Hanson J, Bonnen PE
Clin Exp Med 2024 Jan 27;24(1):17. doi: 10.1007/s10238-023-01259-y. PMID: 38280023Free PMC Article
Azizi G, Bagheri Y, Tavakol M, Askarimoghaddam F, Porrostami K, Rafiemanesh H, Yazdani R, Kiaee F, Habibi S, Abouhamzeh K, Mohammadi H, Qorbani M, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2018;18(5):537-545. doi: 10.2174/1871530318666180413110216. PMID: 29651973

Clinical prediction guides

Azizi G, Bagheri Y, Tavakol M, Askarimoghaddam F, Porrostami K, Rafiemanesh H, Yazdani R, Kiaee F, Habibi S, Abouhamzeh K, Mohammadi H, Qorbani M, Abolhassani H, Aghamohammadi A
Endocr Metab Immune Disord Drug Targets 2018;18(5):537-545. doi: 10.2174/1871530318666180413110216. PMID: 29651973

Recent systematic reviews

Hanson J, Bonnen PE
Clin Exp Med 2024 Jan 27;24(1):17. doi: 10.1007/s10238-023-01259-y. PMID: 38280023Free PMC Article

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