Implementation of a dried blood spot-based Newborn screening program for adenosine deaminase deficiency: An initial...

Adenosine deaminase (ADA) deficiency is a congenital error of purine metabolism and major cause of severe combined immunodeficiency (SCID). This life-threatening hereditary disorder requires early diagnosis and intervention. However, conventional SCID newborn screening (NBS) using T-cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) may fail to identify ADA-deficient cases. Therefore, ADA-specific NBS is needed to ensure comprehensive detection.

We analyzed ADA-specific NBS data in Kumamoto, Japan (October 2024-August 2025). Deoxyadenosine concentration in dried blood spots (DBSs) was measured using tandem mass spectrometry. The cutoff value for deoxyadenosine was set at 0.06 μmol/L. When the deoxyadenosine concentration remained above this cutoff after repeated testing, a second DBS was requested. Newborns with persistently elevated levels were referred for immunological testing.

A total of 9550 newborns were screened. The rate of second DBS requests was 4/9550 (0.04%). Among these, only one newborn showed persistent elevation of deoxyadenosine level and was referred for immunological testing. The newborn was diagnosed with ADA deficiency, confirmed using biochemical and genetic analyses, despite having normal TREC and KREC levels. No false positive cases were identified in the final screening outcome.

This is the first report of an ADA-specific NBS program in Japan. ADA deficiency was successfully diagnosed with no false positives in the final screening outcome, and it is highly unlikely that the present case could have been captured by conventional SCID screening. These findings highlight the need for ADA-specific screening in NBS to enable early diagnosis and improve outcomes.