SCID

Question 1

What is SCID?

Answer 1

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.

Question 2

Presentation of SCID?

Answer 2

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)

Question 3

Causes of SCID?

Answer 3

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

Question 4

Omenn syndrome?

Answer 4

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

Question 5

Management of SCID?

Answer 5

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.