Analysis of newborn screening and diagnosis of inherited metabolic diseases in Xinjiang
Objective To explore the application value of tandem mass spectrometry combined with next-generation sequencing technology in the diagnosis of inborn errors of metabolism(IEM)in Xinjiang,China,and to explore the disease spectrum and genetic characteristics of IEM in Xinjiang,China.Methods Tandem mass spectrometry was used to screen 64980 neonatal dried blood spot samples from Urumqi Maternal and Child Healthcare Hospital from November 2018 to De-cember 2022.Further differential diagnosis is required for infants who have tested positive for screening and are yet to be diagnosed,and use next generation sequencing for genetic analysis.Results The number of newborns who were initially screened positive was 232 who were still positive after recall,and 67 of them underwent NGS sequencing for further diagnosis.Finally,a total of 42 neonates and 2 family members were diagnosed with inherited metabolic diseases,with an overall posi-tive predictive value(PPV)of 18.10％.The overall incidence of neonatal genetic metabolic diseases in Xinjiang was 1∶1547(42/64980).The incidences of abnormal amino acid metabolism,abnormal organic acid metabolism and fatty acid oxidation disorders were 1∶2320(28/64980),1∶7220(9/64980)and 1∶12996(5/64980),respectively.Phenylketonuria and methyl-malonic acidemia are the most common types of IEM in the region,accounting for 76％(32/42)of all confirmed neonates.Hyperphenylalanineemia PAH gene c.158G＞A and c.688G＞A point mutations are the most common;Four mutation types of MMACHC gene including c.609G＞A,c.567dupT,c.217C＞T and c.445_446delTG were found in the MMACHC gene of me-thylmalonic acidemia in this region,and six mutation types including c.729_730insT were found in MMUT gene.And 16 mu-tation types in seven genes:HPD,PCCB,IVD,GCDH,MCCC1,SLC22A5,and ACADS.Conclusion In this study,tandem mass spectrometry and next-generation sequencing technology were used for the screening and diagnosis of inherited meta-bolic diseases,which provided effective clinical guidance and data basis for expanding the popularization and application of newborn screening,genetic screening and IEM genetic counseling in Xinjiang.
inherited metabolic diseasestandem mass spectrometrynext-generation sequencing
NETL
NSTL
万方数据
