2.1 Adenosine deaminase (ADA) deficiency leads to build up of toxic metabolites that causes severe combined immunodeficiency (SCID) and a systemic metabolic defect. ADA–SCID is an ultra-rare condition caused by inheritance of a faulty gene from both parents, which impairs production of the enzyme ADA. The main features of SCID are due to a lack of lymphocytes resulting in a compromised immune system.
2.2 Signs and symptoms of ADA–SCID typically occur in the first year of life (although about 10% to 15% of people with ADA–SCID have a later onset). Immunodeficiency has the greatest effect on morbidity and mortality, and leads to a high risk of serious and life-threatening recurrent infections. The systemic metabolic defect also causes non-immunological manifestations, including insufficient weight and height gain, cognitive and behavioural problems, and deafness. ADA–SCID has a profound effect on health-related quality of life and, if left untreated, infants die before school age. Quality of life is affected by developmental delay, chronic diarrhoea, failure to thrive, recurrent infections and neurological impairments. People whose condition is untreated must be isolated to reduce the risk of infection. The patient experts highlighted that isolation has a profound effect on both patient and carer quality of life.
2.3 ADA–SCID accounts for about 10% to 15% of all diagnoses of severe combined immunodeficiency. The overall annual incidence is estimated to be between 1 in 200,000 and 1 in 1,000,000 live births, although the incidence varies widely between populations. In England, it is most common in people with Irish traveller and Somalian family origins. The company estimated that 3 people a year would be diagnosed with ADA–SCID in England.
2.4 ADA–SCID is currently treated with haematopoietic stem cell transplants (HSCTs), which can restore the immune system if successful. There is a risk of the transplanted cells rejecting the new host (graft-versus-host disease), so donors are chosen based on how close a human leukocyte antigen (HLA) match they are. The first choice HSCT is from an HLA‑matched related donor (MRD). If an MRD is not available, an HLA‑matched unrelated donor (MUD) would be considered, or a haploidentical donor (who can be a parent) if a MUD is not available. Immediately after diagnosis, people have enzyme replacement therapy with polyethylene glycol-modified adenosine deaminase every week. This is intended to stabilise the condition and provide a 'bridge' to an HSCT, but is not currently licensed in England. In England, 2 highly specialist centres, at Great Ormond Street Hospital and Great North Children's Hospital diagnose, assess and treat ADA–SCID.