Omenn syndrome

Omenn syndrome is an autosomal recessive form of severe combined immunodeficiency (SCID) characterized by erythroderma (skin redness), desquamation (peeling skin), alopecia (hair loss), chronic diarrhea, failure to thrive, lymphadenopathy (enlarged lymph nodes), eosinophilia, hepatosplenomegaly, and elevated serum IgE levels.^[1][2][3] Patients are highly susceptible to infection and develop fungal, bacterial, and viral infections typical of SCID. In this syndrome, the SCID is associated with low IgG, IgA, and IgM and the virtual absence of B cells. There is an elevated number of T cells, but their function is impaired.^[1] Omenn syndrome has been found to be caused by mutations in the RAG1 or RAG2 genes.^[1][3] Additional causative genes have been identified.^[1] Early recognition of this condition is important for genetic counseling and early treatment. If left untreated, Omenn syndrome is fatal. The prognosis may be improved  with early diagnosis and treatment with  compatible bone marrow or cord blood stem cell transplantation.^[1][2]

Omenn syndrome is a genetically heterogeneous condition (meaning that it may be caused by a number of different genes). While most cases are attributed to mutations in the RAG genes (RAG-1 and RAG2 genes have been mapped to chromosome band 11p13), recent reports describe Omenn syndrome in the absence of RAG mutations.^[1][3] Omenn syndrome caused by mutations in ARTEMIS, ADA, ILRA2, ILRA7, CHD7, and DNA ligase 4 have been described in the medical literature. Some cases of Omenn syndrome have also been found in association with 22q11 microdeletion syndrome.^[1]

Infants with Omenn syndrome typically present shortly after birth, usually by 3 months of age. This is similar to other types of severe combined immunodeficiency (SCID). The characteristic skin findings (red and peeling skin), chronic diarrhea, and failure to thrive often precede the onset of infections. Life-threatening infections caused by common viral, bacterial, and fungal pathogens occur next. Lymphadenopathy and hepatosplenomegaly, both symptoms unique to Omenn syndrome, develop next.^[1]

The standard treatment for Omenn syndrome is bone marrow transplantation or cord blood stem cell transplantation.^[1][2] General care for any patient with severe combined immunodeficiency (SCID), including Omenn syndrome, includes isolation to prevent infection and meticulous skin and mucosal hygienic practices while the patient is awaiting stem cell reconstitution. Broad-spectrum antibiotics may be administered parenterally while cultures and body fluid analyses are in progress. Parenteral nutrition may also be provided as therapy for diarrhea and failure to thrive.^[1] A detailed description of therapeutic options is provided in the referenced eMedicine article.