SCID

Severe combined immunodeficiency (SCID) is a group of genetic disorders characterized by defects in T cell development and, in most forms, B and NK cell function, leading to profound immunosuppression. Infants typically present in the first months of life with severe or recurrent infections, chronic diarrhea, poor appetite, and failure to thrive. Without treatment, SCID is usually fatal in the first year or two.

SCID is caused by mutations in many genes involved in lymphocyte development and signaling. The condition is commonly X-linked due to mutations in IL2RG (the common gamma chain), accounting for about half of cases, with autosomal recessive forms arising from ADA deficiency, RAG1/2, JAK3, IL7R, DCLRE1C, and others. The genetic defect disrupts T cell development; B and NK cells may be absent or markedly reduced, with low immunoglobulins and poor responses to vaccines. Newborn screening by T-cell receptor excision circle (TREC) testing detects many cases before infections occur.

Diagnosis involves immunophenotyping showing T cell lymphopenia, along with reduced or absent B and/or NK cells, hypogammaglobulinemia, and impaired lymphocyte proliferation to mitogens. Definitive diagnosis is by genetic testing.

Treatment focuses on restoring immune function. Hematopoietic stem cell transplantation (HSCT) is curative for many subtypes and is most successful when performed early, ideally before severe infections. Supportive measures include antimicrobial prophylaxis, IV immunoglobulin, and infection avoidance. ADA-deficient SCID can be treated with enzyme replacement therapy (PEG-ADA). Gene therapy has shown promise for several subtypes in selected patients.

SCID is uncommon but life-threatening; early diagnosis and treatment markedly improve outcomes. Long-term prognosis depends on the specific genetic defect, age at treatment, infectious burden, and treatment quality.