Application of Region 4 Stork system in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency by tandem mass spectrometry / 中华检验医学杂志

ABSTRACT

Objective:To investigate the application feasibility of Region 4 Stork (R4S) system, an international collaborative newborn screening data platform, combined with cut-off value analysis in the neonatal screening for very long chain acyl-CoA dehydrogenase deficiency (VLCADD) by tandem mass spectrometry (MS/MS).Methods:The retrospective study was performed in 2, 040 072 neonates screened by MS/MS in Neonatal Screening Center of Zhejiang Province, China from October 2013 to July 2018. Nine hundred and ten cases were determined and identified as suspected positive VLCADD neonates by traditional cut-off method of tandem mass spectrometry. The original data of these 910 screened neonates were further analyzed by R4S system. Based on clinical diagnosis and ACADL gene test results, the screening efficiency between two methods was statistically compared.Results:The data of 910 suspected VLCADD-positive cases interpreted by cut-off method were further analyzed by R4S system, and the positive interpretation was reduced to 238 cases (including 9 confirmed positive cases). A total of 16 different mutations were found in ACADL gene sequencing among the confirmed children. The screening false positive rate (FPR) declined from 0.44‰ (901/2 040 072) to 0.11‰ (229/2 040 072), the rate of positive predictive value (PPV) increased from 0.99% (9/910) to 3.78% (9/238), and the specificity increased from 99.96% (2 039 162/2 040 063) to 99.99% (2 039 834/2 040 063). There was a statistically significant difference between cut-off method alone and cut-off method combined R4S system analysis (χ2=393.5, P<0.05). Conclusions:The R4S system combined with cut-off method applied in VLCADD neonatal screening by MS/MS can effectively improve screening performance, reduce false positive rate, and has certain value in clinical application.