Peer-reviewed article
Implementation of a dried blood spot-based Newborn screening program for adenosine deaminase deficiency: An initial experience in Japan.
Kinoshita Y, Kido J, Sawada T, Sugawara K, Mizukami T et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study describes the first newborn screening program in Japan specifically testing for adenosine deaminase (ADA) deficiency, a rare genetic disorder that causes severe immunodeficiency. Researchers screened 9,550 newborns in Kumamoto using dried blood spot samples and identified one case of ADA deficiency that would have been missed by standard screening methods. The program had no false positive results, demonstrating that ADA-specific screening can successfully detect this life-threatening condition early.
Key points
- One case of ADA deficiency was successfully identified among 9,550 newborns screened
- The identified case had normal TREC and KREC levels, meaning it would have been missed by conventional SCID screening
- Only 0.04% of newborns required a second dried blood spot test
- No false positives were identified in the final screening outcome
- ADA deficiency was confirmed through biochemical and genetic analyses
Limitations
This is an initial implementation report from a single region in Japan over a 10-month period with a small number of positive cases, so the findings may not be generalizable to other populations or inform the optimal cutoff values for widespread use. The report does not describe follow-up outcomes for the identified case or long-term effectiveness of early detection.
Abstract
Background 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. Methods 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. Result 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. Conclusions 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.
Findings the Hub has extracted
Each claim below is labelled by its type of design and links back to this report.
- Intervention
- ADA-specific newborn screening using deoxyadenosine concentration measurement in dried blood spots via tandem mass spectrometry with a cutoff value of 0.06 μmol/L
- Population
- Newborns in Kumamoto, Japan (n=9,550)
Key finding
One case of ADA deficiency was successfully identified (1/9,550 newborns)