Enhancing newborn screening sensitivity and specificity for missed NICCD using selected amino acids and acylcarnitines

Peiyao Wang; Lingwei Hu; Yuhe Chen; Duo Zhou; Shasha Zhu; Ting Zhang; Ziyan Cen; Qimin He; Benqing Wu; Xinwen Huang

doi:10.1186/s13023-025-03532-7

Orphanet Journal of Rare Diseases (Jan 2025)

Enhancing newborn screening sensitivity and specificity for missed NICCD using selected amino acids and acylcarnitines

Peiyao Wang,
Lingwei Hu,
Yuhe Chen,
Duo Zhou,
Shasha Zhu,
Ting Zhang,
Ziyan Cen,
Qimin He,
Benqing Wu,
Xinwen Huang

Affiliations

Peiyao Wang: Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health
Lingwei Hu: Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health
Yuhe Chen: Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health
Duo Zhou: Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health
Shasha Zhu: Department of Pediatric Health, Taizhou Women and Children’s Hospital
Ting Zhang: Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health
Ziyan Cen: Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health
Qimin He: School of Geography Science and Geomatics Engineering, Suzhou University of Science and Technology
Benqing Wu: Children’s Medical Center, University of the Chinese Academy of Sciences-Shenzhen Hospital
Xinwen Huang: Department of Genetics and Metabolism, Children’s Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health

DOI: https://doi.org/10.1186/s13023-025-03532-7
Journal volume & issue: Vol. 20, no. 1
pp. 1 – 10

Abstract

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Abstract Purpose To enhance the detection rate of Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) through newborn screening (NBS), we analyzed the metabolic profiles of missed patients and proposed a more reliable method for early diagnosis. Methods In this retrospective study, NICCD patients were classified into “Newborn Screening” (64 individuals) and “Missed Screening” (52 individuals) groups. Metabolic profiles were analyzed using the non-derivatized MS/MS Kit, and genetic mutations were identified via next-generation sequencing and confirmed by Sanger sequencing. Receiver Operating Characteristic (ROC) analysis evaluated the predictive value of amino acids and acylcarnitines in dried blood spots (DBS) for identifying missed patients including 40 missed patients and 17,269 healthy individuals, with additional validation using 12 missed patients and 454 healthy controls. Results The age of diagnosis was significantly higher in the “Missed Screening” group compared to the “Newborn Screening” group (74.50 vs. 18.00 days, P A. Conclusions Combining multiple metabolic markers during NBS significantly improves sensitivity and specificity for detecting missed NICCD cases. However, the relationship between genetic mutations and missed cases remains unclear.

Published in Orphanet Journal of Rare Diseases

ISSN: 1750-1172 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine
Website: https://ojrd.biomedcentral.com

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