Peer-reviewed article
Comparison of Four Screening Markers [(C16 + C18:1)/C2, C14/C3, C12/C0, and C12/C2] for Carnitine Palmitoyltransferase II Deficiency in the Nationwide Newborn Screening Program in Japan.
Tajima G, Ishige N, Hanai J, Konomura K ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This study compared four blood screening markers used to detect carnitine palmitoyltransferase II deficiency in newborn screening programs in Japan. The researchers tested how well each marker could identify babies with this serious metabolic disorder while avoiding false alarms. The marker C12/C2 performed best at reducing false-positive results, though some cases of the milder form of the disease may still be missed. The findings suggest that changing screening markers could improve the accuracy of newborn screening for this condition.
Key points
- False-positive results occur frequently in current newborn screening for CPT II deficiency
- C12/C2 and C14/C3 markers showed superior performance compared with currently used markers (C16 + C18:1)/C2 and C14/C3
- C12/C2 had an area under the precision-recall curve of 0.711 compared to 0.569 for C14/C3
- When myopathic form cases were included, performance of all markers decreased markedly
- C12/C2 appears effective for reducing false-positive results while accepting that some myopathic cases may still be missed
Limitations
The study uses historical case data and does not evaluate the clinical outcomes or impact of screening with different markers on affected children. It cannot determine the real-world consequences of missed diagnoses or false positives on child health and family management.
Abstract
False-positive results are known to occur frequently in newborn screening (NBS) for carnitine palmitoyltransferase II (CPT II) deficiency, highlighting the need to identify appropriate screening markers. The present study aimed to compare the performance of two markers currently used in NBS for CPT II deficiency, (C16 + C18:1)/C2 and C14/C3, with two promising alternative markers, C12/C0 and C12/C2. We analyzed non-patient data from the 2023 fiscal year NBS program together with patient data for CPT II deficiency and very-long-chain acyl-CoA dehydrogenase deficiency derived from previously reported case series. Marker performance was assessed using precision-recall curves, including an analysis in which patients with the myopathic form of CPT II deficiency who passed NBS using (C16 + C18:1)/C2 and C14/C3 were reclassified as true positives. The area under the precision-recall curve values for C12/C2 and C14/C3 were 0.711 (95% confidence interval, 0.492-0.923) and 0.569 (0.341-0.779), respectively, indicating superior performance compared with the other markers. When cases with the myopathic form of CPT II deficiency were included as true positives, the performance of all markers decreased markedly. Although some patients with the myopathic form are still likely to be missed, C12/C2 appears to be an effective marker for reducing false-positive results.