Omenn syndrome

Omenn syndrome
Classification and external resources
Specialty hematology
ICD-10 D81.2 (ILDS D81.210)
OMIM 603554
DiseasesDB 32676
eMedicine ped/1640
MeSH D016511
Orphanet 39041

Omenn syndrome is an autosomal recessive severe combined immunodeficiency[1] associated with hypomorphic missense mutations in immunologically relevant genes of T-cells (and B-cells) as recombination activating genes (RAG1 and RAG2), IL-7 Receptor α gene (IL7Rα), DCLRE1C-Artemis, RMRP-CHH, DNA-Ligase IV, common gamma chain, WHN-FOXN1, ZAP-70 and complete DiGeorge anomaly (DiGeorge Syndrome; CHARGE).

Symptoms

Redness and scaliness of the entire skin on a 5-month-old female infant
A 5-month-old female infant with Omenn syndrome; she has red, scaly skin all over her body.

The symptoms are very similar to graft-versus-host disease (GVHD). This is because the patients have some T cells with limited levels of recombination with the mutant RAG genes. These T cells are abnormal and have a very specific affinity for self antigens found in the thymus and in the periphery. Therefore, these T cells are auto-reactive and cause the GVHD phenotype.

A characteristic symptom is chronic inflammation of the skin, which appears as a red rash[2] (early onset erythroderma). Other symptoms include eosinophilia, failure to thrive, swollen lymph nodes, swollen spleen, diarrhea, enlarged liver, low immunoglobulin levels (except immunoglobulin E, which is elevated), low T cell levels, and no B cells.[3]

Genetics

Omenn syndrome has an autosomal recessive pattern of inheritance.

Omenn syndrome is caused by a partial loss of RAG gene function and leads to symptoms similar to severe combined immunodeficiency syndrome, including opportunistic infections. The RAG genes are essential for gene recombination in the T-cell receptor and B-cell receptor, and loss of this ability means that the immune system has difficulty recognizing specific pathogens.[2] For the Omen Syndrom is the loss of T-cell function the important defect, that leads to engraftment of maternal lymphocytes in the foetus and a co-existence of clonally expanded autologous and transplacental-acquired maternal lymphocytes.[4] Omenn syndrome can occasionally be caused in other recombination genes, including IL-7Rα and RMRP.[3]

Treatment

The only treatment for Omenn syndrome is bone marrow transplantation. Without treatment, it is rapidly fatal in infancy.[2] The disease can be cured by bone marrow transplantation.[3]

See also

References

  1. ↑ Santagata S, Villa A, Sobacchi C, Cortes P, Vezzoni P (2000). "The genetic and biochemical basis of Omenn syndrome". Immunol Rev. 178: 64–74. doi:10.1034/j.1600-065X.2000.17818.x. PMID 11213808.
  2. 1 2 3 Parham, Peter (2009). The Immune System (3rd ed.). Taylor & Francis Group. p. 128. ISBN 9781136977107.
  3. 1 2 3 Geha, Raif; Notarangelo, Luigi (2012). Case Studies in Immunology: A Clinical Companion (6th ed.). Garland Science. ISBN 978-0-8153-4441-4.
  4. ↑ Lev A, Simon AJ, Ben-Ari J, Takagi D, Stauber T, Trakhtenbrot L, Rosenthal E, Rechavi G, Amariglio N, Somech R (2014). "Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency.". Clin Exp Immunol. 176 (3): 380–6. doi:10.1111/cei.12273. PMID 24666246.
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