Severe combined immunodeficiency (SCID) is the most severe primary immunodeficiency disorder. Patients with SCID have almost no immunity to infections. It may be caused by a number of different genetic abnormalities that result in absent or dysfunctional T-cells and impaired B-cell function.
Presentation
SCID typically presents in the first few months of life with:
- Persistent severe diarrhoea
- Failure to thrive
- Frequent and severe infections (e.g., severe candidiasis, severe chickenpox or Pneumocystis jirovecii)
- Illness following live vaccines (e.g., BCG and MMR)
- Omenn syndrome (see below)
Causes
Over 50% of cases are caused by a mutation in a gene on the X chromosome that encodes the common gamma chain, a shared subunit of interleukin receptors, resulting in absent T-cells and natural killer cells, and non-functional B-cells. This has X-linked recessive inheritance.
Other gene mutations that can lead to SCID include:
- JAK3 gene mutations
- Mutations leading to adenosine deaminase deficiency
Omenn Syndrome
Omenn syndrome is a rare cause of SCID. It is the result of a mutation in the recombination-activating gene (RAG1 or RAG2), which encodes important proteins in T and B-cells. It has autosomal recessive inheritance.
Omenn syndrome is caused by abnormally functioning T-cells that attack the body’s tissues, leading to features of:
- A red, scaly, dry rash (erythroderma)
- Hair loss (alopecia)
- Diarrhoea
- Failure to thrive
- Lymphadenopathy
- Hepatosplenomegaly
- Eosinophilia and raised IgE
Management
SCID is fatal unless successfully treated. Management should be in a specialist immunology centre. Management involves:
- Infection prevention measures
- Treating infections that occur
- Prophylactic antibiotics, antifungals and antivirals
- Immunoglobulin therapy
- Avoiding live vaccines
- Haematopoietic stem cell transplantation (the definitive treatment)
Last updated April 2026
Now, head over to members.zerotofinals.com and test your knowledge of this content. Testing yourself helps identify what you missed and strengthens your understanding and retention.
