Infectious Disease: Severe Combined Immunodeficiency Syndrome

Question 1

Defintion

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

Aetiology

Answer 2

• > 50% = 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 3

Signs and symptoms

Answer 3

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 e.g:
= severe and later fatal chickenpox,
= Pneumocystis jiroveci pneumonia = Cytomegalovirus
- Unwell after live vaccinations such as the BCG, MMR and nasal flu vaccine
- Omenn syndrome

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

Treatment

Answer 5

Fatal unless successfully treatment
Treated in specialist immunology centre:
- Treating underlying infections,
- Immunoglobulin therapy,
- Minimising the risk of new infections with a sterile environment,
- Avoiding live vaccines and performing haematopoietic stem cell transplantation