Summary
SCID is the name given to a group of rare, inherited disorders that cause major abnormalities of the immune system. They form part of a larger group of conditions known as primary immunodeficiencies. The immune system abnormalities in SCID lead to greatly increased risks of infection and other complications that are life-threatening. Affected infants become unwell within the first few months of life, and before modern medication and treatments were available, most affected babies did not survive beyond their first year. Today, doctors understand much more about SCID. Treatment is now available that can reduce the risk of serious infection, and in many cases, cure the disorder.
There are many different types of SCID, each with different genetic causes. However, infants affected by the various types of SCID have many features in common and these are described here. In all infants affected by SCID, specialised white blood cells, known as lymphocytes, are missing or not functioning properly. The three main types of lymphocytes that can be affected are called T-cells, B-cells and natural killer (‘NK’) cells.
Continuing developments and improvements are transforming the lives of children with SCID. Advances in diagnostic techniques and genetic technology, improved treatments and better medications enable many children with SCID to proceed through stem cell transplant safely. It is likely that gene therapy will continue to develop and become applicable to more types of SCID.
SCID is an inherited condition, meaning it is passed on in families in the same way as physical characteristics, such as eye colour, are passed from parent to child. It is caused by a mistake (or mutation) in a child’s genetic makeup.
Specialists in genetics and genetic counselling are on hand to talk through the inheritance of SCID with you if needed, and Immunodeficiency UK has a separate information leaflet devoted to the genetics of primary immunodeficiency. In infants affected by SCID, a genetic mistake results in the absence or malfunction of a protein that is necessary for normal development and/or function of the immune system.
Many different genes can be affected, each causing a different type of SCID. Recent developments in genetics mean that doctors are now often able to make a specific SCID diagnosis. The names given to the different types of SCID are based on the particular protein or gene that is affected. Some of the more frequently encountered types include common gamma chain deficiency, adenosine deaminase (ADA) deficiency, JAK 3 kinase deficiency, MHC class II deficiency, and recombinase activating gene (RAG) deficiency. Although the management and treatment of infants with SCID is usually very similar for all types, it is important to know the exact cause: (a) because in some conditions there may be specific treatments available, and (b) to allow accurate genetic counselling for future pregnancies.
There are two specialist centres in the UK that treat children with SCID – Great Ormond Street Hospital (GOSH) in London, and the Great North Children’s Hospital (GNCH) in Newcastle. Treatment will begin when the child is referred to one of these centres.
The immediate priorities will be to provide an environment which protects from infection, to perform appropriate tests and assessments, and to start treatment for infection and other protective measures. Subsequently, possible treatments that can correct the defect will be discussed. These include haematopoietic stem cell transplantation (HSCT, or SCT; also known as BMT) and gene therapy. HSCT is the most usual treatment, while gene therapy is only suitable for a small number of specific conditions and is still undergoing clinical trials.
Starting treatment
Your child will be admitted to a room or an area with ‘filtered air’ (to remove germs). He or she will be confined to this room and will not be able to mix with other children or go to the ward playroom. You will be able to stay with your child and will be encouraged to continue to feed, care for and play with him or her as much as you want. Visitors will be kept to a minimum, and no one who has an infection will be allowed to visit. You will be told about the ways that you can avoid passing on infection, such as washing your hands thoroughly.
Further blood tests will be performed to confirm the diagnosis and type of SCID. More specialised tests will subsequently be carried out to determine the precise genetic abnormality. Other investigations will also be necessary to identify any undetected infection, including chest x-rays, scans and tests on samples of blood, urine, faeces and mucus from the throat.
Most children with SCID will have similar symptoms and will receive the same treatments whatever the type of SCID. In most cases, a ‘central line’ (sometimes called a central venous catheter or Hickman® line) will be inserted. This is a silicone tube which is put into a large vein and fixed to the skin surface, usually on the chest. It requires a small operation under general anaesthetic, but it allows blood to be taken and intravenous medicine to be given without the need for any needles and is sometimes also used to give intravenous nutrition.
Medication
Antibiotics, antiviral and antifungal medicines will be needed to protect against serious infection. Most medicines can be given in the form of syrups. If the baby has an active infection, it may be necessary to give the medicines into a vein, through a drip (or through the central venous catheter).
Immunoglobulin (antibody) therapy
Babies affected by SCID are not able to produce their own antibodies to fight infection. The missing antibodies are replaced by giving treatment with immunoglobulin.
Immunoglobulin is a solution of human antibodies which have been purified from normal blood donations. It provides temporary protection against infection and it is given either intravenously (into a vein) or subcutaneously (injection into the skin).
Your child will receive regular immunoglobulin therapy from the time of diagnosis. As it is derived from donor blood, giving immunoglobulin carries a very small risk of transmitting infections. You will have the chance to discuss immunoglobulin therapy in more detail, and the method by which it will be given, with the immunologist or nurse specialist before treatment starts. Further information about immunoglobulin treatment can be found in a range of our leaflets.
Blood transfusions
It may be necessary to give blood, platelet or plasma transfusions. It is important that these treatments are given, but some precautions are needed. Specially prepared ‘irradiated’ blood is given. Irradiating donor blood preserves the red blood cells and platelets but removes any immune cells that could cause a bad reaction. The donor blood is also screened to ensure it does not contain CMV, which could cause problems for a child with SCID. Any blood, platelet or plasma transfusion will be labelled ‘CMV negative’ and ‘Irradiated’.
CMV, breast feeding and nutrition
CMV is a very common virus in the general population, with approximately 50 to 80 per cent of adults in the UK testing positive for the virus. It is spread through bodily fluids, such as saliva, urine and breast milk. In most cases, CMV does not cause any symptoms, but in some people, flu-like symptoms, including a high temperature, sore throat and swollen glands, may occur. Once you have had CMV, the virus stays in your body but is inactive, and in a healthy person does not cause any further problems.
CMV can be serious for infants with SCID. If a mother is breastfeeding a child with SCID, a blood test will be taken from the mother to see if she is CMV-positive because the virus can be transmitted in breast milk. While waiting for the result, mothers are supported to express their milk. The result normally comes back after 24 to 48 hours. If the result is positive, it is advised to stop breastfeeding, owing to the risk of transmitting CMV to the baby, and formula milk feeds will be recommended. If a baby with SCID is not thriving, extra calories, vitamins and minerals may be needed. These can be given in special drinks or medicines. If your baby is feeding poorly, extra feeds can be given through a nasogastric tube (a tube inserted into the stomach through the nose).
However, in some cases, it may be necessary to give feeding called TPN (total parenteral nutrition), in which all the nutrients and calories are given intravenously, directly into the bloodstream through a central venous catheter.
Vaccination
In many cases, some early infant vaccines will already have been given before the diagnosis of SCID is recognised. Most of these are completely safe and do not cause any problems because they are not live vaccines. However, it is important for live vaccines to be avoided in infants with SCID. These include live polio vaccine (no longer part of the routine immunisation schedule in the UK), BCG and measles/mumps/rubella (MMR). If your child or another family member has received a live polio vaccine due to vaccination in another country, then the doctors should be made aware. The Rotavirus vaccine, which has recently been added to the routine UK schedule, is given in the first few months of life, and is also a live vaccine. It may result in the vaccine strain of the virus persisting in the gut of infants with SCID. If your baby has received rotavirus vaccine, this will be tested as part of the initial set of investigations.
Once the diagnosis of SCID is established, no further routine vaccines are recommended until treatment has been completed. Regular immunoglobulin replacement treatment will provide protection against a large number of germs, including those covered by routine vaccines.
Prolonged hospitalisation, separation from extended family, blood tests and uncomfortable procedures will contribute to a great deal of stress and anxiety and even guilt for parents of a child with SCID. Support is available from psychologists, social workers and Immunodeficiency UK.
It may be possible for your child to go home for a period of time before he or she goes ahead with corrective treatment. In this situation, the immunology team will contact local doctors and community nurses beforehand to make arrangements if treatments need to be given at home or in the local hospital.
Most parents are delighted to get home, but it can be a worrying time. Anxiety about catching or passing on an infection can make life very stressful. The hospital team, nurses and support groups will provide you with guidance on protecting your child from infection, keeping the house clean and coping with diet and medication. If you are worried at any time, you are always able to ring the hospital and speak to an immunologist or a nurse.
Please take a look at our webpage on counselling and emotional support for parents of children affected by PID.
Haematopoietic stem cell transplantation (HSCT)
Brief information is provided about HSCT here, but much more detailed information can be provided by the bone marrow transplant (BMT) unit and on our website.
In most cases, HSCT offers the only long-term cure for SCID. HSCT aims to replace the faulty immune system with an immune system from a healthy donor. Stem cells, from which all the cells of the immune system develop, can be obtained from healthy bone marrow (bone marrow transplantation; BMT), or in some cases, from umbilical cord blood or donor blood. Bone marrow, blood or umbilical cord blood can be taken from a suitable, healthy donor and given by transfusion into a vein to a child with SCID.
An HSCT is not an operation like a heart or kidney transplant. Stem cells contained in the donor bone marrow are able to find their way from the bloodstream to your child’s bone marrow, where they start to produce healthy blood cells. An HSCT does involve a number of risks, and complications can arise afterwards – some of which are temporary, others of which can be life-threatening. You will have the opportunity to discuss this in detail with an immunologist and transplant consultant on several occasions.
Soon after the diagnosis of SCID is confirmed, blood samples will be collected from members of the family to determine the tissue type of each member. If a family member is found to have an identical tissue type to the affected baby, they will be selected to be the donor. There is a 1 in 4 (25 per cent) chance that full siblings will have identical tissue types. If there is no suitable family donor an unrelated donor will be sought from the worldwide donor registries.
Donating bone marrow involves having a general anaesthetic but it is a relatively minor procedure. Donating stem cells obtained from blood involves taking some preparatory medication (which is given by injection) and undergoing a procedure known as ‘apheresis’. Both types of donation involve minimal risk to the donor.
Once a donor has been identified, the family will meet members of the transplant team, who will ensure that the family has ample opportunity to see the transplant unit, discuss worries and ask questions. In most cases, chemotherapy drugs are needed to prepare the body to receive a new immune system, reducing the chance of rejection of the new bone marrow by the child’s own immune cells. If a perfectly matched bone marrow donor has been found within the immediate family, then chemotherapy is not always necessary. Not all children will receive exactly the same drug combinations.
Gene therapy
Gene therapy aims to correct the underlying genetic abnormality by replacing the faulty gene in immune cells with a normal copy. It is currently undergoing clinical trials in selected patients who have certain specific conditions. It has been successful in correcting the immune deficiency in a small number of children affected by X-linked SCID and the ADA-deficient form of SCID. It may also be available soon for some other genetic forms of SCID. For the child, gene therapy is a relatively straightforward procedure and if successful offers a cure.
Gene therapy involves taking stem cells from an affected child’s blood or bone marrow. These are then manipulated in the laboratory, inserting a normal copy of the defective genes using complex technology. Once corrected, the cells are returned a few days later by transfusion into the child. As in a stem cell transplant, these new stem cells find their way to the bone marrow, where they start to produce healthy immune cells. This is known as somatic gene therapy – altered genetic material is only present in cells derived from the infused stem cells and cannot be passed on to future generations.
People worry about the idea of gene therapy because of the possibilities of eugenics (generating an improved population through the selection of its best characteristics for breeding). Manipulating genes that can be passed on to offspring is known as germ-line gene therapy and is not permitted by law.
Further information about gene therapy can be found here and will also be provided by the gene therapy team as needed.
Continuing developments and improvements are transforming the lives of children with SCID.
Advances in diagnostic techniques and genetic technology, improved treatments and better medications enable many children with SCID to proceed through stem cell transplant safely. It is likely that gene therapy will continue to develop and become applicable to more types of SCID.
Genetic counselling
In many cases, the genetic mistake causing SCID can now be identified. This means that accurate genetic counselling is available for the immediate and extended family and that 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 can be found here.
Newborn screening for SCID
Unless there is a previous family history of SCID, most infants with SCID are only diagnosed after problems with serious infection occur. Early diagnosis of SCID has been shown to significantly improve survival (to over 90 per cent). This is because infants diagnosed soon after birth can be started on preventative medications and other measures taken to prevent serious infections from very early on. Much work is being undertaken towards introducing newborn screening for SCID worldwide, and several countries now have established screening programmes for SCID. This is not currently available in the UK. However, we continue to work closely with the UK National Screening Committee (UKNSC) and are hopeful that a national screening programme for SCID will be approved in the UK soon.
You can download our information booklet here.
