Severe combined immunodeficiency (SCID) is the most severe condition causing immunodeficiency. Children with SCID have almost no immunity to infections. It is a syndrome caused by a number of different genetic disorders that result in absent or dysfunctioning T and B cells.
Presentation
SCID will present in the first few months of life with:
- Persistent severe diarrhoea
- Failure to thrive
- Opportunistic infections that are more frequent or severe than in healthy children, for example severe and later fatal chickenpox, Pneumocystis jiroveci pneumonia and cytomegalovirus
- Unwell after live vaccinations such as the BCG, MMR and nasal flu vaccine
- Omenn syndrome (see below)
Causes
More than 50% of cases are caused by a mutations in the common gamma chain on the X chromosome that codes for interleukin receptors on T and B cells. This has X-linked recessive inheritance.
There are many other gene mutations that can lead to SCID including:
- JAC3 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 (RAG 1 or RAG 2) that codes for important proteins in T and B cells. It has autosomal recessive inheritance.
The syndrome is caused by abnormally functioning and deregulated T cells that attack the tissues in the fetus or neonate. This leads the classic features of Omenn syndrome:
- A red, scaly, dry rash (erythroderma)
- Hair loss (alopecia)
- Diarrhoea
- Failure to thrive
- Lymphadenopathy
- Hepatosplenomegaly
Management
SCID is fatal unless successfully treated. Management should be in a specialist immunology centre. Management involves treating underlying infections, immunoglobulin therapy, minimising the risk of new infections with a sterile environment, avoiding live vaccines and performing haematopoietic stem cell transplantation.
Last updated January 2020