Newborn screening, genetic analysis, and long-term follow-up of 89 cases with short-chain acyl-CoA dehydrogenase deficiency (SCADD)

IF 1.8 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports Pub Date : 2026-03-01 Epub Date: 2026-02-10 DOI:10.1016/j.ymgmr.2026.101292

GuLing Qian , Chen Liu , YanHua Xu , Duo Zhou , Chi Chen , BenQing Wu , XinWen Huang

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引用次数: 0

Abstract

Objective

This study aimed to delineate the neonatal screening landscape, incidence, tandem mass spectrometry (MS/MS)-based metabolic signatures, ACADS gene variant spectrum, and long-term clinical outcomes of short-chain acyl-CoA dehydrogenase deficiency (SCADD) in newborns from Zhejiang Province, China.

Methods

A retrospective cohort study was conducted on 4,667,883 newborns in Zhejiang screened between November 2013 and August 2025. Acylcarnitine profiles in dried blood spots were analyzed by MS/MS. Urinary organic acids and ACADS gene variants were detected via gas chromatography–mass spectrometry (GC–MS) and high-throughput sequencing, respectively. Confirmed SCADD patients underwent longitudinal follow-up to evaluate growth, neurodevelopment, and biochemical parameters.

Results

Initial screening identified 500 infants with elevated butyrylcarnitine (C4) or C4/ propionylcarnitine (C3) ratios; 89 were confirmed as SCADD, corresponding to an incidence of 1 in 52,448 (1.9 per 100,000). All patients were asymptomatic during the neonatal period. Among the 26 patients who underwent urinary GC/MS, 25 (96.2%) presented with elevated ethylmalonic acid (EMA) levels. Fifty-one ACADS variants were identified, with missense variants (46/51, 90.2%) being the most prevalent; the top three variants were c.1031 A > G (28.1%), c.164C > T (13.5%), and c.1130C > T (11.2%).

Conclusions

The incidence of SCADD in Zhejiang is 1 in 52,448, with c.1031 A > G and c.164C > T as the most frequent ACADS variants; and most screen-detected SCADD cases remain asymptomatic.

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89例短链酰基辅酶a脱氢酶缺乏症新生儿筛查、遗传分析及长期随访

目的研究浙江省新生儿短链酰基辅酶a脱氢酶缺乏症（SCADD）的筛查情况、发病率、基于串联质谱（MS/MS）的代谢特征、ACADS基因变异谱和长期临床结果。方法对2013年11月至2025年8月在浙江省筛查的4667883名新生儿进行回顾性队列研究。采用质谱联用法分析干血斑的酰基肉碱谱。采用气相色谱-质谱（GC-MS）和高通量测序分别检测尿有机酸和ACADS基因变异。经证实的SCADD患者接受纵向随访，以评估生长、神经发育和生化参数。结果初步筛查发现500例婴儿丁基肉碱（C4）或C4/丙基肉碱（C3）比值升高；89例确诊为SCADD，发病率为1 / 52,448（1.9 / 100,000）。所有患者在新生儿期均无症状。在26例接受尿GC/MS检查的患者中，25例（96.2%）出现乙基丙二酸（EMA）水平升高。共鉴定出51个ACADS变异，其中错义变异最为普遍（46/51,90.2%）；前三名是c.1031在G(28.1%)、c.164C祝辞T(13.5%),和c.1130C比;T(11.2%)。结论浙江省SCADD患病率为1 / 52448，患病率为1031A >； G和c.164C >； T是最常见的ACADS变体；大多数筛查到的SCADD病例仍然无症状。

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

Molecular Genetics and Metabolism Reports Biochemistry, Genetics and Molecular Biology-Endocrinology

CiteScore

4.00

自引率

5.30%

发文量

105

审稿时长

33 days

期刊介绍： Molecular Genetics and Metabolism Reports is an open access journal that publishes molecular and metabolic reports describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, sequence reports, brief communication reports and letters to the editor are considered.