Symptoms normally appear in the first six months of life. The disorder can also lead to various non-immunological health problems, including a failure to grow and develop normally, hearing loss and liver and kidney problems. Children born with ADA-SCID are severely impaired in their ability to fight infections. The toxin builds up and destroys infection-fighting lymphocytes. Without this enzyme, the body is unable to break down a toxic substance called deoxyadenosine. Children born with this disorder have virtually no immunity to fight off everyday bacterial, fungal or viral infections.ĪDA-SCID is an ultra-rare immune disorder, caused by a faulty gene inherited from both parents that stops the production of adenosine deaminase. The European Medicines Agency (EMA) has recommended granting a marketing authorisation in the European Union (EU) for a new gene therapy for the treatment of patients with adenosine-deaminase-deficient severe combined immunodeficiency (ADA-SCID), who have no matching donor for a stem cell transplant. Survival rates after allogenic hematopoietic stem cell transplantation or gene therapy are high.Orphan-designated Strimvelis to offer treatment option for patients with ADA-SCID who have no suitable stem cell donor

Without treatment, SCID due to ADA deficiency that presents in infancy usually results in early death. Prognosis depends on the severity of the disease. Treatment is based on allogenic hematopoietic stem cell transplantation (HSCT), enzyme replacement therapy with pegylated adenosine deaminase enzyme or gene therapy by infusion of CD34+ marrow cells that have been transduced with an ADA-containing vector. Prenatal diagnosis can be carried out through mutation analysis or measurement of enzyme activity in trophoblasts cultured from chorionic villus sampling or in cultured amniocytes. Differential diagnosisĭifferential diagnosis includes all forms of SCID. Diagnosis can be confirmed by raised levels of dATP and reduced S-adenosyl homocysteine hydrolase (SAHH) activity in red cells and elevated amounts of deoxyadenosine in urine. Diagnostic methodsĭiagnosis is based on evidence of low or undetectable ADA activity in erythrocytes in combination with evidence of a marked reduction of T, B and NK cell counts when compared to age-matched healthy controls.

The extraimmune manifestations are caused by toxic levels of purine metabolites that result from the deficiency of ADA. SCID due to ADA deficiency is caused by mutations in the ADA gene (20q13.11). Patients may also present with extraimmune manifestations (including neurodevelopmental deficits, behavioral disorders, sensorineural deafness, and skeletal and hepatic abnormalities) as a result of the systemic nature of ADA expression. Ten to 15% of patients have a delayed clinical onset by age 6-24 months, and a smaller percentage have a partial form of ADA deficiency with later onset between ages 4 years and adulthood, both types showing less severe infections and gradual immunologic deterioration. The most common form presents in infancy with severe and recurrent opportunistic infections (including respiratory tract infections and candidiasis), failure to thrive, and usually results in early death. SCID due to ADA deficiency has a variable clinical presentation. Its annual incidence is estimated to be between 1/200,000 and 1/1,000,000 live births. SCID due to ADA deficiency accounts for 10-15% of all cases of SCID.

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