Newborn screening for inherited metabolic diseases and genetic variant spectrum analysis in northwestern Guizhou,China

CHEN Wengao; CAI Yuxin; PENG Dan; CHEN Li; LI Shouqun; WANG Juan; YANG Rukan; YU Chaowen

doi:10.11852/zgetbjzz2026-0028

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Chinese Journal of Child Health Care ›› 2026, Vol. 34 ›› Issue (11) : 1196-1202. DOI: 10.11852/zgetbjzz2026-0028

Birth Defect Screening and Genetic Diagnosis

Newborn screening for inherited metabolic diseases and genetic variant spectrum analysis in northwestern Guizhou,China

CHEN Wengao¹, CAI Yuxin², PENG Dan¹, CHEN Li¹, LI Shouqun¹, WANG Juan¹, YANG Rukan¹, YU Chaowen²

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Abstract

Objective To investigate the implementation effect of newborn screening for inherited metabolic diseases (IMDs) in Northwestern Guizhou, and to characterize the genetic mutation spectrum, so as to understand the regional epidemiological features and provide evidence for early diagnosis and intervention of birth defects. Methods This retrospective study included 46 078 newborns screened in eight counties or districts of Bijie in northwestern Guizhou between September 2023 and September 2024.Dried blood spot amino acids and acylcarnitines were analyzed by tandem mass spectrometry to screen for 33 IMDs.Screen-positive newborns were recalled for repeat testing and genetic diagnosis.The screen-positive rate, genetically confirmed case detection rate, and pathogenic variant distribution were analyzed. Results Among 46 078 neonates screened by MS/MS, 270 cases were positive, yielding a positive rate of 0.59%.Genetic testing was completed in 249 newborns, and 26 were confirmed to have IMDs, yielding an overall detection rate of 0.56‰.The confirmed disorders comprised hyperphenylalaninemia (n=7), short-chain acyl-CoA dehydrogenase deficiency (n=7), 2-methylbutyryl-CoA dehydrogenase deficiency (n=6), hypermethioninemia (n=5), and citrin deficiency (n=1).Twenty-two variants in six genes were identified, including a novel MAT1A frameshift variant[c.680dup (p.Arg228GlnfsTer38)]and two candidate recurrent ACADS variants. Conclusions The detection rate of IMD in northwestern Guizhou is relatively high.Hyperphenylalaninemia, short-chain acyl-CoA dehydrogenase deficiency, and 2-methylbutyryl-CoA dehydrogenase deficiency are the most frequently identified disorders, and evidence of ethnic clustering is observed.These disorders should be prioritized in local newborn screening programs.Genetic diagnosis and counseling should be strengthened in areas with ethnically clustered populations, while surveillance of newly identified and recurrent variants should be continued to optimize birth-defect prevention and control strategies.

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newborn screening / inherited metabolic diseases / birth defects / tandem mass spectrometry / gene diagnosis

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CHEN Wengao, CAI Yuxin, PENG Dan, CHEN Li, LI Shouqun, WANG Juan, YANG Rukan, YU Chaowen. Newborn screening for inherited metabolic diseases and genetic variant spectrum analysis in northwestern Guizhou,China[J]. Chinese Journal of Child Health Care. 2026, 34(11): 1196-1202 https://doi.org/10.11852/zgetbjzz2026-0028

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