Newborn Screening for PDE: A High-Throughput Lab Workflow Using 2-OPP, Oxo-PIP, and Pipecolate

A methods-and-performance study supports adding PDE-ALDH7A1 to existing newborn screening systems by measuring 2-OPP and confirmatory markers in a single FIA-MS/MS assay.

If PDE-ALDH7A1 can be diagnosed and treated earlier, many families hope newborn screening (NBS) could reduce time-to-treatment. The challenge is building a test that is accurate, affordable, and compatible with the high-throughput reality of newborn screening labs.

This study evaluates 2-OPP as a primary NBS marker and tests whether adding secondary markers (pipecolate and 6-oxo-pipecolate, also called oxo-PIP) improves real-world performance. The authors describe a butylated flow-injection analysis tandem mass spectrometry (FIA-MS/MS) approach designed to fit within existing NBS infrastructure.

The deeper-science and lab-performance detail is in how cutoffs are tuned: the paper explores percentile-based thresholds for 2-OPP and shows how pairing an elevated 2-OPP with an elevated secondary marker can increase positive predictive value while keeping sensitivity high. The ability to multiplex all three analytes in one assay matters because it makes a PDE screen more practical for widespread adoption.

Why this matters

It offers a concrete, scalable route to “find PDE before the first seizure” in some infants, which is the dream behind adding PDE to NBS panels.

Limitations

This is not yet a universal policy change. Larger prospective studies are still needed to finalize cutoffs and confirm performance across diverse populations.

Sources

• “Advancing Neonatal Screening for Pyridoxine-Dependent Epilepsy-ALDH7A1 Through Combined Analysis of 2-OPP, 6-Oxo-Pipecolate and Pipecolate in a Butylated FIA-MS/MS Workflow.” International Journal of Neonatal Screening (2025). DOI: 10.3390/ijns11030059 (PubMed: 40843901; Free full text: PMC12372136)

Safety note: This summary is educational and not medical advice.