Screening for neonatal inherited metabolic disorders by tandem mass spectrometry in Guangzhou

Objective: To analyze the screening results for inherited metabolic disorders (IMD) in newborns by tandem mass spectrometry (MS/MS) in Guangzhou. Methods: A total of 272 117 newborns in Guangzhou from Jan 2015 to Dec 2020 were screened for IMD by MS/MS in Guangzhou Newborn Screening Center. When the primary screening was positive, the newborns and their mothers were recalled. For those with positive in re-examination, the biochemical and related genetic analysis were required for confirmation. The screening results, clinical characteristics and outcomes of the confirmed cases were retrospectively analyzed and the performance was optimized. Results: Among 272 117 neonates, 1808 (0.66%) cases were positive in primary screening, and 1738 cases (96.13%) were recalled for review. The median clinical diagnosis time was 15 d after birth. A total of 79 cases of IMD were diagnosed, including 23 with aminoacidopathy, 17 with disorder of organic acid metabolism and 39 with fatty acid oxidation disorders, involving 21 diseases. The incidence rate was 1/3444 in newborns, and the positive predictive value of 4.5%. Four false negative cases were found, all of them were citrin deficiency. The common diseases were primary carnitine deficiency (26.6%), methylmalonic aciduria (12.7%) and phenylalanine hydroxylase deficiency (11.4%). The mothers of 32 cases were confirmed, including 30 cases of primary carnitine deficiency, 1 case of isobutyl-coenzyme A dehydrogenase deficiency and 1 case of 3-methylcromaryl coenzyme A carboxylase deficiency. The detection rate was 1/2451 in total population. During the follow-up, most patients remain asymptomatic, except for 5 severe cases who died early (1 case of maple syrup urine disease, 2 cases of isolated methylmalonic acidurmia, and 2 cases of carnitine-acylcarnitine translocase deficiency); and 10 cases of organic acid metabolism disorders developed mild psychomotor developmental retardation. After optimizing the screening indicators, the number of initial screening positives dropped to 903, and the positive predictive value increased to 9.1%, and no confirmed cases were missed. Conclusion: The incidence rate of fatty acid oxidation disorders is high in Guangzhou. A variety of IMD can be effectively screened out by MS/MS, and the screening performance can be improved by optimizing screening indicators.