To explore the value of combined detection of arginylsuccinic acid (Asa) and citrulline (Cit) levels by flow injection tandem mass spectrometry (MS/MS) in the screening of neonatal arginylsuccinic aciduria (ASLD).

A retrospective analysis was conducted. Among a total of 621 686 newborns screened using the first-generation MS/MS kit by detecting Cit level at the Nanjing Neonatal Screening Center from January 1, 2014 to March 21, 2024, 1 case of ASLD was diagnosed. From March 2024 to August 2025, a total of 87 729 newborns were screened using the second-generation MS/MS kit by detecting Asa and Cit levels, and 1 case of ASLD was diagnosed. Genetic testing was adopted for screen-positive children, and the clinical data were comprehensively evaluated to determine the value of Asa in screening for ASLD.

Among 87 729 newborns, 8 were initially screen-positive for Asa, of whom 1 was confirmed to have ASLD after recall and confirmatory testing. The initial screening positivity rate for Asa was 0.01%, with a sensitivity of 100.00%, specificity of 99.99%, and positive predictive value of 12.50%. In the confirmed case, Asa level was elevated, whereas Cit remained within the reference range.

Asa demonstrates favorable screening efficacy for ASLD. It can indicate risk even when Cit is within the reference range and may help reduce the risk of missed detection when using Cit alone.