Summary
This information has been produced jointly between Immunodeficiency UK, Great Ormond Street Hospital (GOSH) and the Great North Children’s Hospital. It covers the causes, sign and symptom, diagnosis and treatment of the X-linked specific form of severe combined immunodeficiency (X-linked SCID). We advise that the material should be read in conjunction with our general overview information on SCID.
X-SCID is caused by a mistake (mutation) in a gene on the X chromosome. The affected gene codes for a protein known as the ‘common gamma chain’ (γc). γc is very important for normal development and functioning of a number of cells that are vital for a healthy immune system. These include T cells, natural killer (NK) cells and B cells. In X-SCID, γc is either absent or not working, and this results in a severely abnormal immune system.
The signs and symptoms in babies with X-SCID are the same as in all forms of SCID. You can find an overview here.
Initial investigations are the same as for all forms of SCID and are described here.
There are a number of features that might suggest a diagnosis of X-SCID. A detailed family history is important. If the baby is a boy and there is a history of affected boys in the family (including unexplained infant deaths), X-SCID may be likely. In addition, the basic immunology tests looking at the presence of T, NK and B cells may show a pattern suggestive of X-SCID. The pattern doctors are looking for is ‘T- B+ NK-’, meaning that T cells and NK cells are absent or very low in number, while B cells are present in normal numbers. If this pattern is confirmed, particularly when the family history is suggestive, X-SCID is likely.
The next step is to perform specialised tests to look for the γc protein and to carry out genetic testing to look for a mutation in the γc gene. Results of these tests are usually available within a few days.
The basic approach to looking after an infant with X-SCID is the same as for all forms of SCID, as described in our information here.
In the UK there are two specialist centres in the country that provide definitive treatment for children with SCID – Great Ormond Street Hospital (GOSH) in London, and the Great North Children’s Hospital (GNCH) in Newcastle. Definitive treatment begins when the child is referred to one of these centres. Initial stabilisation and treatment under advice may begin in a referring specialist children’s hospital or treatment centre.
When the time comes to discuss definitive (curative) treatment, there may be a choice between haematopoietic stem cell transplant (HSCT) and gene therapy. X-SCID is one of the small number of conditions for which clinical trials in gene therapy have been successful. The decision regarding which treatment is best will depend on the availability of well-matched donors for HSCT. This will require extensive discussion with the transplant and gene therapy teams.
It can be helpful to meet other families who have a child with SCID and who have undergone HSCT or gene therapy. Speak to your immunology team, who may be able to arrange a meeting with a suitable family.
Genetic counselling is important not only for the immediate family but also for the extended family on the mother’s side, because other relatives might be carrying the faulty gene. For females identified as carriers, prenatal diagnosis is possible for future pregnancies. Referral to local genetic counselling services can be arranged, and in some situations a joint counselling appointment with a genetics specialist and an immunologist can be helpful. More information about the genetic aspects of primary immunodeficiency is available here.
You can download our information booklet here.
