Genomic sequencing enhances metabolic newborn screening in Thailand

IF 2.3 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinical biochemistry Pub Date : 2026-03-01 Epub Date: 2026-02-20 DOI:10.1016/j.clinbiochem.2026.111107

Chulaluck Kuptanon , Pawinee Innark , Kannikar Punnapum , Supaporn Nammoonnoy , Rotjanapan Pankanjanato , Maliwan Numnuan , Orapan Sripichai , Sukanya Wattanapokayakit , Punna Kunhapan , Ekke Kunphol

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引用次数: 0

Abstract

Objectives

Thailand expanded metabolic newborn screening (NBS) program to include inherited metabolic diseases (IMDs) using tandem mass spectrometry since 2022. Molecular testing has increasingly been used as a second-tier tool to clarify ambiguous results or confirm diagnosis for abnormal metabolic NBS screening. This study aimed to assess the performance of whole genome sequencing (WGS) as a second-tier test for abnormal IMD screening results in Thai neonates.

Design and methods

From August 2023 to December 2024, neonates with abnormal IMD screens were recruited for WGS, in addition to the routine biochemical confirmation.

Results

Seventy-four newborns and 27 mothers were included in the study. Biochemical testing confirmed 40 IMDs, 12 borderline, and 21 normal cases, while WGS identified 3 additional IMDs and 8 carriers. Among 73 newborns, WGS identified 41 IMD cases and 32 normal (22 carriers), achieving 95% sensitivity, 100% specificity, 100% positive predictive value, and 97% negative predictive value. WGS refined disease subtypes, resolved borderline amino acid abnormalities, and guided individualized management. Limitations included missed large structural variants and lower sensitivity for detecting single heterozygous variants, emphasizing that molecular testing complements rather than replaces biochemical confirmation.

Conclusions

WGS as a second-tier test enhances diagnostic precision, clarifies ambiguous NBS results, supports early, targeted intervention, and precision care in Thai newborns.

查看原文本刊更多论文

基因组测序增强了泰国新生儿代谢筛查。

目的：自2022年起，泰国扩大了新生儿代谢筛查（NBS）项目，将遗传代谢疾病（IMDs）纳入其中。分子检测越来越多地被用作二级工具，用于澄清不明确的结果或确认异常代谢NBS筛查的诊断。本研究旨在评估全基因组测序（WGS）作为泰国新生儿异常IMD筛查结果的二级检测的性能。设计与方法：2023年8月至2024年12月，在常规生化确认的基础上，招募IMD筛查异常的新生儿进行WGS。结果：74名新生儿和27名母亲被纳入研究。生化检测确认40例imd， 12例边缘性imd， 21例正常病例，WGS检测发现3例imd和8例携带者。在73例新生儿中，WGS检测出41例IMD， 32例正常（22例携带者），敏感性95%，特异性100%，阳性预测值100%，阴性预测值97%。WGS细化疾病亚型，解决临界氨基酸异常，指导个体化治疗。局限性包括遗漏大的结构变异和检测单个杂合变异的灵敏度较低，强调分子检测是补充而不是取代生化确认。结论：WGS作为二级检测提高了诊断的准确性，澄清了不明确的NBS结果，支持泰国新生儿的早期、有针对性的干预和精确护理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical biochemistry 医学-医学实验技术

CiteScore

5.10

自引率

0.00%

发文量

151

审稿时长

25 days

期刊介绍： Clinical Biochemistry publishes articles relating to clinical chemistry, molecular biology and genetics, therapeutic drug monitoring and toxicology, laboratory immunology and laboratory medicine in general, with the focus on analytical and clinical investigation of laboratory tests in humans used for diagnosis, prognosis, treatment and therapy, and monitoring of disease.