Newborn screening by tandem mass spectrometry in Nanjing: a retrospective analysis of 175 767 cases / 中华围产医学杂志

ABSTRACT

Objective:To analyze the detection of neonatal inherited metabolic diseases in Nanjing.Methods:We researched the results of 175 767 newborns by tandem mass spectrometry from December 2013 to July 2018. Amino acids, acylcarnitines, and succinylacetone were detected by non-derivatized tandem mass spectrometry to screen the abnormity of newborn amino acid, organic acid, or fatty acid oxidation metabolism disease. Gene panels based on high throughput sequencing technology were carried out to detect gene mutation of positive neonates. Descriptive statistics were used to analyze all the data.Results:The positive rate of primary screening was 2.1% (3 691/175 767), 3 598 of 3 691 positive cases were recalled. At last, 62 cases of the inherited metabolic disease were diagnosed. Among them, there were 35 cases of amino acid metabolism disease, 12 cases of organic acid metabolism disorder, and 15 cases of fatty acid metabolism defect. The total incidence of neonatal inherited metabolic disease was 0.035 3%, among which amino acid metabolic diseases were 0.019 9%, organic acid metabolic diseases were 0.006 8%, and fatty acid metabolic diseases were 0.008 5%. The diseases with the highest incidence were phenylalanine hydroxylase deficiency (0.015 9%), methylmalonic acidemia (0.005 1%), and primary carnitine deficiency (0.005 1%). Among 62 children, 51 (82.2%) were diagnosed by gene diagnosis (including 17 cases of phenylalanine hydroxylase deficiency and 34 cases of other inherited metabolic diseases). Another 11 children with phenylalanine hydroxylase deficiency refused gene diagnosis. Two pathogenic mutations were found in 17 children with phenylalanine hydroxylase deficiency. Two pathogenic mutations were found in 29 of the other 34 children with inherited metabolic disease, which were from their parents, while only one pathogenic mutation was found in the other five children, of which two cases with hypermethioninemia were autosomal dominant inheritance.Conclusions:Neonatal inherited metabolic diseases with high incidence in Nanjing are phenylalanine hydroxylase deficiency, methylmalonic acidemia, and primary carnitine deficiency. Some cases screened by tandem mass spectrometry only showed abnormal screening indicators. No specific clinical symptoms were found during follow-up, and further follow-up was needed.