Adenosine deaminase deficiency (ADA-SCID)
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An infant with recurrent severe infections (pneumonia, chronic diarrhea, candidiasis) has absent T, B, and NK cells. Skeletal abnormalities are present on X-ray.
AR; ADA
- Severe combined immunodeficiency (SCID)
- T-B-NK- phenotype
- Costochondral abnormalities on X-ray
- Toxic accumulation of deoxyadenosine
- On RUSP (TREC-based SCID screening)
- Newborn screening flags low/absent TRECs (T-cell receptor excision circles), the universal SCID assay
- Lymphopenia with absent T, B, and NK cells (T-B-NK- pattern) on flow cytometry
- Low/absent erythrocyte ADA enzyme activity with elevated deoxyadenosine and dATP
- Confirmatory ADA molecular testing
- HSCT, gene therapy (Strimvelis), PEG-ADA enzyme replacement
ADA normally breaks down Adenosine to Inosine: when ADA is deficient, deoxyadenosine accumulates and is converted to increased dATP, which is lymphotoxic (toxic to both B and T cells, explaining the T-B-NK- SCID phenotype).
NBS: decreased TRECs: ADA-SCID is detected on newborn screening by decreased T-cell receptor excision circles (TRECs), the same assay used for all forms of SCID. One of the purine metabolism disorders (along with Lesch-Nyhan syndrome). Strictly, ADA is a purine catabolism (degradation) enzyme, whereas HPRT in Lesch-Nyhan is the classic salvage-pathway defect.