Application of high-throughput sequencing in screening neonatal genetic metabolic diseases
Objective To analyze the application value of high-throughput sequencing(NGS)in screening neonatal genetic metabolic diseases.Methods This was a prospective study.One hundred and eighty-five critical cases of acidosis or encephalopathy of unknown causes hospitalized in Neonatal Intensive Care Unit(NICU),Huangshi Maternal and Child Health Hospital from January 2021 to June 2023 were selected,including 95 boys and 90 girls.The heel blood was collected from all the subjects.The biochemical screening(tandem mass spectrometry and time-resolved immunofluorescence)and NGS screening were performed.The NGS screening was designed to capture 202 genes related to genetic metabolism,and the mutation pathogenesis was interpreted according to the relevant guidelines.The positive abnormal sites were verified by the Sanger sequencing.Results Of the 185 neonates,7.57％(14/185)were preterm infants and 8.11％(15/185)were from assisted reproduction;15(8.10％)were positive in the biochemical screening,and 5(2.70％)were positive in the re-detection after recall,including 1 case of decreased glucose-6-phosphate dehydrogenase(G6PD),1 case of decreased 17-hydroxyprogesterone(17α-OHP),1 case of decreased thyroid stimulating hormone(TSH),and 2 cases of increased phenylalanine.Among the 185 newborns,6 cases(3.24％)were positive in NGS,including 4 cases of DOUX 2,MATIA,G6PD,CYP21A2 compound heterozygous mutations and 2 cases of PAH mutation.In addition,except for the positive ones,there were 45 newborns(24.32％)who had recessive mutations and 140 negative newborns(72.43％).The results of the two screens were consistent with each other in 5 cases and not in 1 case;3 of the 6 patients were confirmed,including 1 case of hyperphenylalaninemia,1 case of 21-hydroxylase deficiency congenital adrenocortical hyperplasia,and 1 case of congenital hypogonadism.Taking the clinical diagnosis as the reference,the medical records to be confirmed were included in the true positive;the biochemical screening sensitivity was 83.3％,the specificity was 100.0％,and the positive predictive value was 100.0％;the NGS screening's sensitivity was 100.0％,the specificity 100.0％,and the positive predictive value was 100.0％.Conclusion The NGS screening accuracy is high,so it can comprehensively diagnose neonatal genetic metabolic diseases.
High throughput sequencingNewbornsGenetic screeningMetabolismSensitivity
万方数据
维普
