OBJECTIVES: ADA deficiency, being an ultra-rare, autosomal recessive condition, is a paediatric emergency. More than 80% of diagnoses occur during the first few months of life and can be life-threatening and chronically debilitating if left untreated. This review aimed to summarise published data on the clinical, humanistic, and economic burden in patients with ADA-SCID.

METHODS: MEDLINE^® and EMBASE^® databases were searched to systematically identify studies reporting the clinical, humanistic, or economic burden of ADA-SCID in a global population, published in English in the last 10 years.

RESULTS: A total of 28 studies (clinical burden, n=25; humanistic burden, n=2; economic burden, n=1) were included. The annual incidence of ADA-SCID across studies varied from approximately 1 in 250,000 to 1 in 600,000 live births and accounted for an estimated 10–20% of all SCID cases. Reported clinical manifestations included profound lymphoproliferative disorders, recurrent opportunistic infections, failure to thrive, non‐immunological features such as myeloid impairments, mental retardation, sensorineural hearing deficits, and hepatic dysfunction. Patients with ADA-SCID had significantly lower intelligent quotient levels (p<0.001) and a greater incidence of behavioural problems compared with the general population and other SCID genotypes. Currently, limited treatments are available; they include enzyme-replacement, bone marrow transplantation, and gene therapy. The evidence identified in the review suggested poor overall survival rates even after varied treatment options (range: 29% to 71%); however, patients treated with gene therapy have shown a 100% survival rate (2 studies). The review identified only one economic study; this reported the average cost per infant not receiving early hematopoietic cell transplantation as $450,000 (range: $200,000 to $750,000), based on expert opinion. Published data on the direct and indirect costs of managing ADA-SCID were absent.

CONCLUSIONS: Current evidence suggests a considerably high clinical and humanistic burden among ADA-SCID patients. Adequate quantification of the economic burden of ADA-SCID is warranted.