Severe combined immunodeficiency (SCID) is a group of heterogeneous disorders with similar clinical pictures but variable defects resulting in severe dysfunction of T and B cells.

Disease occurs in 1 per 50 000 to 100 000 births. Over 15 genetic mutations have been linked to this syndrome, and the majority of cases are autosomal recessive in their inheritance. Around one-fifth are due to the X-linked form of SCID, which affects only males. This form is due to a mutation of the common gamma chain of interleukin receptors for IL-2, 4, 7, 9, and 15. There are few to no T cells (CD3) and natural killer (NK) cells. Variable levels of B cells make nonfunctional antibodies. Other prominent types include adenosine deaminase (ADA) deficiency and RAG1/RAG2 deficiency. Two to three percent of SCID cases are caused by deficiency in the DNA-repair enzyme Artemis, resulting from mutations in DCLRE1C. Other forms of SCID have varying immunologic abnormalities, and diagnosis is made on direct gene analysis.

Failure to thrive (poor feeding and low weight gain), chronic diarrhea and infections (especially pneumonias, otitis media, and skin infections), mucocutaneous candidiasis, and skin eruptions mark the course of disease. Transplacental maternal engraftment that gives rise to a graft-versus-host disease (GVHD) clinical picture occurs in about half of patients.

The average age of symptom onset is 2 months. Without therapy, death from infection usually occurs in the first 2 years of life.