A condition called CD3 delta SCID is caused by a mutation in the CD3D gene, which prevents the production of the CD3 delta protein that is needed for the normal development of T cells from blood stem cells. The choice between HSCT or gene therapy will depend on whether there are well-matched donors available for transplant and will be discussed at length between the parents and the transplant and gene therapy teams. The differences between these different gene therapy options will be discussed with the families in detail. It can be used until a more definitive therapy is available, such as haematopoietic stem cell transplant (HSCT) or gene therapy.Ĭlinical trials of gene therapy for ADA deficiency are ongoing in Europe and the USA, with Great Ormond Street Hospital being one of the centres where this treatment is available.Ī related, commercial gene therapy treatment called Strimvelis has been recently approved by NICE and is available to families as an alternative treatment in Milan. PEG-ADA treatment corrects the ADA and adenosine levels in the blood, and usually leads to gradual improvement and partial correction of immune function. It is given as a weekly injection into a muscle, for instance, the thigh muscle. This is often referred to as enzyme replacement therapy. However, in contrast to other forms of SCID, it is possible to replace the missing enzyme using a medication known as PEG-ADA. The first stages of treatment and precautions are the same as in all forms of SCID. The need for other investigations will depend on whether other systems of the body are involved. A psychologist will also carry out a developmental assessment. If ADA deficiency is confirmed, it is important to assess hearing as early as possible because of the high risk of deafness. Additionally, the levels of adenosine can be measured and will be much higher than normal. The level of ADA enzyme activity in the blood can be measured and is usually less than one per cent of the normal levels seen in healthy children. Doctors refer to this pattern of SCID as ‘T -, B -, NK – SCID’, and this is highly suggestive of a diagnosis of ADA-SCID. Breathing difficulties can also occur in infants with ADA-SCID without any detectable infection.īlood count testing shows a very low lymphocyte count, and basic immunology tests show very low or absent levels of T, B and NK lymphocytes. Infants with typical early onset ADA-SCID have poor growth and frequent, severe and unusual infections, such as pneumonia with an organism called Pneumocystis jirovecii (a yeast-like fungus) that does not usually cause illness in healthy individuals. There may also be problems with other body systems, including the kidneys, liver and lungs. In some cases there may be a low level of working ADA enzyme, leading to a less severe ‘delayed’ onset of combined immune deficiency (CID) – please refer to our separate information on CID. However, the ADA gene is important in all cells of the body, and therefore patients with ADA-SCID often also have symptoms and signs outside the immune system. White blood cells (especially lymphocytes, and more specifically T cells, B cells and natural killer (NK) cells) that are important for a healthy immune system are very sensitive to these toxic effects and fail to develop normally, leading to SCID. This prevents cells from dividing effectively. Lack of the ADA enzyme causes a build-up of a toxic substance called deoxyadenosine. Enzymes are protein substances that help speed up chemical reactions in the body. ĪDA-SCID is caused by mistakes (mutations) in the ADA gene, which result in absent or very low levels of the enzyme ADA. More information about autosomal recessive inheritance can be found in our leaflet ‘ Genetic aspects of primary immunodeficiency ’. There may be a family history of previously affected children, particularly if there are first or second-cousin marriages or partnerships in the family. This means that a child has to inherit the faulty gene from both parents to have the condition. It is inherited as an autosomal recessive condition. ADA-SCID is a specific form of severe combined immunodeficiency ( SCID).
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