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WIP DEFICIENCY*WISKOTT-ALDRICH SYNDROME PROTEIN-INTERACTING PROTEIN; gene :WIPF1,Cytogenetic location: 2q31.1  .phenotype :?Wiskott-Aldrich syndrome 2
WIP DEFICIENCY*WISKOTT-ALDRICH SYNDROME PROTEIN-INTERACTING PROTEIN; gene :WIPF1,Cytogenetic location: 2q31.1  .phenotype :?Wiskott-Aldrich syndrome 2
In T lymphocytes, WASP is almost totally complexed with the WASP-interacting protein (WIP). A major function of WIP is to stabilize WASP and prevent its degradation. WASP protein levels, but not mRNA levels, are severely reduced in T cells <ref name="pmid1783416">{{cite journal |vauthors=Pawłowski R |title=Distribution of common phenotypes of sperm diaphorase (DIA3) in the Polish population |journal=Hum. Hered. |volume=41 |issue=4 |pages=279–80 |date=1991 |pmid=1783416 |doi=10.1159/000154013 |url=}}</ref>*
In T lymphocytes, WASP is almost totally complexed with the WASP-interacting protein (WIP). A major function of WIP is to stabilize WASP and prevent its degradation. WASP protein levels, but not mRNA levels, are severely reduced in T cells <ref name="pmid1783416">{{cite journal |vauthors=Pawłowski R |title=Distribution of common phenotypes of sperm diaphorase (DIA3) in the Polish population |journal=Hum. Hered. |volume=41 |issue=4 |pages=279–80 |date=1991 |pmid=1783416 |doi=10.1159/000154013 |url=}}</ref>*
""'''"ATAXIA-TELANGIECTASIA"""'''
===ATAXIA-TELANGIECTASIA===
Ataxia-telangiectasia (AT) is an autosomal recessive characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency,The ATM gene is related to a family of genes involved in cellular responses to DNA damage and/or cell cycle control with defects in both cellular and humoral immunity <ref name="pmid9143686">{{cite journal |vauthors=Lavin MF, Shiloh Y |title=The genetic defect in ataxia-telangiectasia |journal=Annu. Rev. Immunol. |volume=15 |issue= |pages=177–202 |date=1997 |pmid=9143686 |doi=10.1146/annurev.immunol.15.1.177 |url=}}</ref>.*Gene locus :ATM located on  
Ataxia-telangiectasia (AT) is an autosomal recessive characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency,The ATM gene is related to a family of genes involved in cellular responses to DNA damage and/or cell cycle control with defects in both cellular and humoral immunity <ref name="pmid9143686">{{cite journal |vauthors=Lavin MF, Shiloh Y |title=The genetic defect in ataxia-telangiectasia |journal=Annu. Rev. Immunol. |volume=15 |issue= |pages=177–202 |date=1997 |pmid=9143686 |doi=10.1146/annurev.immunol.15.1.177 |url=}}</ref>.*Gene locus :ATM located on  
11q22.3.it it is diagnosed by  
11q22.3.it it is diagnosed by  

Revision as of 15:00, 6 November 2018


Immunodeficiency Main Page

Home

Overview

Classification

Immunodeficiency Affecting Cellular and Humoral Immunity

Combined Immunodeficiency

Predominantly Antibody Deficiency

Diseases of Immune Dysregulation

Congenital Defects of Phagocytes

Defects in Intrinsic and Innate Immunity

Auto-inflammatory Disorders

Complement Deficiencies

Phenocopies of Primary Immunodeficiency

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ali Akram, M.B.B.S.[2], Anmol Pitliya, M.B.B.S. M.D.[3]

Overview

Classification

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Combined Immunodeficiency Diseases with associated or syndromic features
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Congenital thromocytopenia
 
 
DNA Repair Defects
 
 
Immuno-osseous dysplasias
 
 
Thymic Defects with additional congenital anomalies
 
 
Hyper-IgE syndromes(HIES)
 
 
Dyskeratosis congenita (DKC)
 
 
Defects of Vitamin B12 and Folate metabolism
 
 
Anhidrotic Ectodermodysplasia with ID
 
 
Others
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Wiskott Aldrich Syndrome
 
 
 
Ataxia telangiectasia
 
 
 
Cartilage Hair Hypoplasia
 
 
 
DiDeorge Syndrome
 
 
 
Job Syndrome
 
 
 
Dyskeratosis congenita
 
 
 
Transcobalmin 2 deficiency
 
 
 
NEMO deficiency
 
 
 
Purine nucleoside phosphorylase deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XL thrombocytopenia
 
 
 
Nijmegen breakage Syndrome
 
 
 
Schimke Syndrome
 
 
 
TBX1 deficiency
 
 
 
Comel Netherton Syndrome
 
 
 
COATS plus syndrome
 
 
 
Deficiency causing hereditary folate malabsorption
 
 
 
EDA-ID due to IKBA GOF mutation
 
 
 
ID with multiple intestinal atresias
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
WIP deficiency
 
 
 
Bloom syndrome
 
 
 
MYSM1 deficiency
 
 
 
Chromosome 10p13-p14 deletion Syndrome
 
 
 
PGM3 deficiency
 
 
 
SAMD9
 
 
 
Methylene-tetrahydrofolate-dehydrogenase 1 deficiency
 
 
 
 
 
 
 
 
Hepatic veno-occlusive disease with immunodeficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ARPC1B deficiency
 
 
 
PMS2 deficiency
 
 
 
MOPD1 deficiency
 
 
 
CHARGE Syndrome
 
 
 
 
 
 
 
 
SAMD9L
 
 
 
 
 
 
 
 
 
 
 
 
 
Vici Syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunodeficiency with centromeric instability and facial anomalies(ICF1, ICF2, ICF3, ICF4)
 
 
 
EXTL3 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HOIL1 deficiency, HOIP1 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MCM4 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Calcium Channel Defects(ORAI-1 deficiency, STIM1 deficiency)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RNF168 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hennekam-lymphangiectasia-lymphedema syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
POLE1 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
STAT5b deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
POLE2 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Kabuki Syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NSMCE3 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ERCC6L2(Hebo deficiency)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ligase 1 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
GINS1 deficiency
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Wiskott-Aldrich Syndrome

Wiskott–Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder characterized by the triad of eczema, microthrombocytopenia, and severe and often recurrent infections caused by mutation of WASp gene.[1]

  • WASp is involved in actin polymerization and associated coupling of receptor engagement, signaling events, and cytoskeletal rearrangement[2]

Allogeneic stem cell transplantation is the only curative treatment for Wiskott-Aldrich syndrome[3]

*X-linked thrombocytopenia (XLT), sometimes associated with mild eczema and/or infections, was recognized in the 1960s and was suspected to be a variant of WAS.patients with XLT shown to have mutations in the Wiskott-Aldrich syndrome protein gene (WAS).

X-linked thrombocytopenia (XLT) should be suspected in a male with:

  • Congenital thrombocytopenia (5,000-50,000 platelets/mm3)
  • Small platelet size (platelet volume <7.5 fL)
  • Absence of other clinical findings of Wiskott-Aldrich syndrome
  • Family history of one or more maternally related males with a WAS-related phenotype or disorder
  • Decreased or absent WASP by flow cytometry or western blotting
  • Some affected individuals have near-normal amounts of WAS

WIP DEFICIENCY*WISKOTT-ALDRICH SYNDROME PROTEIN-INTERACTING PROTEIN; gene :WIPF1,Cytogenetic location: 2q31.1 .phenotype :?Wiskott-Aldrich syndrome 2 In T lymphocytes, WASP is almost totally complexed with the WASP-interacting protein (WIP). A major function of WIP is to stabilize WASP and prevent its degradation. WASP protein levels, but not mRNA levels, are severely reduced in T cells [4]*

ATAXIA-TELANGIECTASIA

Ataxia-telangiectasia (AT) is an autosomal recessive characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, radiosensitivity, predisposition to lymphoid malignancies and immunodeficiency,The ATM gene is related to a family of genes involved in cellular responses to DNA damage and/or cell cycle control with defects in both cellular and humoral immunity [5].*Gene locus :ATM located on 11q22.3.it it is diagnosed by Diagnosis is usually achieved by examination and identification of both ataxia and oculo-cutaneous telangiectasia. This is then followed by laboratory tests for low levels of IgA, IgG2, IgG4, and IgE. Sufferers may also have a low lymphocyte count and other immunological abnormalities. This can then be followed by cytogenetic and molecular testing to confirm the diagnosis. MRI and CT scans may show signs of cerebellar atrophy.

BLOOM SYNDROME

A number sign (#) is used with this entry because Bloom syndrome (BLM), also referred to here as microcephaly, growth restriction, and increased sister chromatid exchange-1 (MGRISCE1), is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein-like-3 (RECQL3; 604610) on chromosome 15q26.

References

  1. Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. doi:10.2147/TACG.S58444. PMC 4012343. PMID 24817816.
  2. Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. doi:10.2147/TACG.S58444. PMC 4012343. PMID 24817816.
  3. Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M (September 2007). "Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)". Pediatr Hematol Oncol. 24 (6): 393–402. doi:10.1080/08880010701454404. PMID 17710656.
  4. Pawłowski R (1991). "Distribution of common phenotypes of sperm diaphorase (DIA3) in the Polish population". Hum. Hered. 41 (4): 279–80. doi:10.1159/000154013. PMID 1783416.
  5. Lavin MF, Shiloh Y (1997). "The genetic defect in ataxia-telangiectasia". Annu. Rev. Immunol. 15: 177–202. doi:10.1146/annurev.immunol.15.1.177. PMID 9143686.

BLOOM SYNDROME

A number sign (#) is used with this entry because Bloom syndrome (BLM), also referred to here as microcephaly, growth restriction, and increased sister chromatid exchange-1 (MGRISCE1), is caused by homozygous or compound heterozygous mutation in the gene encoding DNA helicase RecQ protein-like-3 (RECQL3; 604610) on chromosome 15q26.