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Immunodeficiency 64(IMD64)

MedGen UID:
1684716
Concept ID:
C5231402
Disease or Syndrome
Synonym: IMMUNODEFICIENCY 64 WITH LYMPHOPROLIFERATION
 
Gene (location): RASGRP1 (15q14)
 
Monarch Initiative: MONDO:0032803
OMIM®: 618534

Definition

Immunodeficiency-64 with lymphoproliferation (IMD64) is an autosomal recessive primary immunodeficiency characterized by onset of recurrent bacterial, viral, and fungal infections in early childhood. Laboratory studies show variably decreased numbers of T cells, with lesser deficiencies of B and NK cells. There is impaired T-cell proliferation and activation; functional defects in B cells and NK cells may also be observed. Patients have increased susceptibility to EBV infection and may develop lymphoproliferation or EBV-associated lymphoma. Some patients may develop features of autoimmunity (summary by Salzer et al., 2016, Mao et al., 2018, and Winter et al., 2018). [from OMIM]

Clinical features

From HPO
B-cell lymphoma
MedGen UID:
86953
Concept ID:
C0079731
Neoplastic Process
A type of lymphoma that originates in B-cells.
Clubbing of fingers
MedGen UID:
3129
Concept ID:
C0009080
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).
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.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
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.
Autoimmune hemolytic anemia
MedGen UID:
1918
Concept ID:
C0002880
Disease or Syndrome
An autoimmune form of hemolytic anemia.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Cervical lymphadenopathy
MedGen UID:
66724
Concept ID:
C0235592
Disease or Syndrome
Enlarged lymph nodes in the neck.
Increased circulating IgA level
MedGen UID:
66800
Concept ID:
C0239984
Finding
An abnormally increased level of immunoglobulin A in blood.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Autoimmune thrombocytopenia
MedGen UID:
116621
Concept ID:
C0242584
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargment (swelling) of a lymph node.
Increased circulating IgM level
MedGen UID:
333454
Concept ID:
C1839972
Finding
An abnormally increased level of immunoglobulin M in blood.
Increased circulating IgG level
MedGen UID:
347032
Concept ID:
C1858977
Finding
An abnormally increased level of immunoglobulin G in blood.
Defective T cell proliferation
MedGen UID:
868165
Concept ID:
C4022557
Cell or Molecular Dysfunction
A reduced ability of a T cell population to expand by cell division following T cell activation.
Anti-thyroid peroxidase antibody positivity
MedGen UID:
1392952
Concept ID:
C4476743
Laboratory or Test Result
The presence of autoantibodies (immunoglobulins) in the serum that react against thyroid peroxidase.
Abnormal CD4:CD8 ratio
MedGen UID:
1619994
Concept ID:
C4531154
Finding
Any abnormality in the relative amount of CD4+ and CD8+ T lymphocytes.
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).
Anti-thyroglobulin antibody positivity
MedGen UID:
1670955
Concept ID:
C4732836
Finding
The presence of autoantibodies (immunoglobulins) in the serum that react to thyroglobulin.
Decreased proportion of CD4-positive T cells
MedGen UID:
1698933
Concept ID:
C5139203
Finding
A reduction in the proportion of CD4-positive T cells relative to the total number of T cells.
Decreased circulating IgG level
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Increased proportion autoreactive unresponsive CD21-/low B cells
MedGen UID:
1772613
Concept ID:
C5421684
Finding
Increased proportion relative to B-lymphocytes of a subset of B lymphocytes characterized by dim/low levels of CD21, i.e., CD21-/low, in flow cytometry, and additionally enriched in autoreactive clones as determined for instance by clonse showing rheumatoid factor (anti-IgG) reactivity and antibodies recognizing cytoplasmic and to a lesser extent nuclear structures.
Mediastinal lymphadenopathy
MedGen UID:
451062
Concept ID:
C0520743
Disease or Syndrome
Swelling of lymph nodes within the mediastinum, the central compartment of the thoracic cavities that contains the heart and the great vessels, the esophagus, and trachea and other structures including lymph nodes.

Professional guidelines

PubMed

Brown LK, Moran E, Goodman A, Baxendale H, Bermingham W, Buckland M, AbdulKhaliq I, Jarvis H, Hunter M, Karanam S, Patel A, Jenkins M, Robbins A, Khan S, Simpson T, Jolles S, Underwood J, Savic S, Richter A, Shields A, Brown M, Lowe DM
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Recent clinical studies

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Prognosis

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