收稿日期: 2025-09-23
网络出版日期: 2026-02-25
基金资助
国家重点研发计划(2017YFC1001700)
Gene mutation analysis，incidence and clinical manifestations of short-chain acyl-CoA dehydrogenase deficiency in newborns in Sichuan area
Received date: 2025-09-23
Online published: 2026-02-25
目的 探讨四川地区新生儿短链酰基辅酶A脱氢酶缺乏症（SCADD）发病率、临床特征及基因突变特点。 方法 针对2017年11月至2024年7月四川省妇女儿童医院新筛实验室收到的113 367例新生儿血液样本以及6例门诊复查阳性患儿，采用串联质谱法检测干血斑中酰基肉碱水平，初筛阳性的患儿于2周内召回，进一步通过尿有机酸、血生化、短链酰基辅酶A脱氢酶基因（ACADS）检测进行确诊。 结果 113 367例新生儿初筛阳性144例，复查阳性20例，确诊SCADD 7例，患病率为1/16 195；6例门诊复查阳性患儿均确诊SCADD，合计确诊13例。患儿临床表现均无明显异常，其中12例血丁酰基肉碱（C4）、C4 与乙酰基肉碱（C2）比值、C4与丙酰基肉碱（C3）比值增高；1例C4正常，但血戊酰基肉碱（C5）、C5与C2比值、C5与C3比值增高。尿有机酸检测乙基丙二酸8例增加，3例正常，2例未做该检查。13例确诊患儿中，2例患儿为纯合突变，其余均为复合杂合突变。发现ACADS基因突变16种，15种为已知突变，分别为：c.989G > A、c.1031A > G、c.1165A > G、c.1054G > A、c.655G > A、c.981-983delGAC、c.974G > A、c.983C > A、c.682G > A、c.802C > G、c.46G > A、c.1192C > T、c.293A > G、c.625G > A、c.1195C > T，1种未报道突变：c.796-7C > A。高频突变为 c.1031A>G（46%），ACADS基因型与乙基丙二酸以及 C4 浓度水平无明显相关。确诊后对患儿进行饮食指导，必要时补充左卡尼汀和维生素B2，随访期间均未出现临床症状，体格及智力发育正常。 结论 四川地区SCADD患病率1/16 195，检测到16种ACADS基因突变位点，通过新生儿筛查确诊的SCADD患儿无明显临床症状，预后较好。
关键词： 短链酰基辅酶A脱氢酶缺乏症; 串联质谱; 基因突变
张钰 , 周婧瑶 , 陈雪莲 , 胡琦 , 杨云霞 , 欧明才 . 四川地区新生儿短链酰基辅酶A脱氢酶缺乏症发病率、临床特征及基因突变分析[J]. 实用医学杂志, 2026 , 42(4) : 677 -684 . DOI: 10.3969/j.issn.1006-5725.2026.04.019
Objective To investigate the incidence， clinical manifestations， and gene mutations of short chain acyl-coenzyme A dehydrogenase deficiency （SCADD） in newborns in the Sichuan area. Methods A total of 113，367 neonatal blood samples that were received by the Neonatal Screening Laboratory of Sichuan Provincial Women′s and Children′s Hospital from November 2017 to July 2024， along with 6 outpatient children who had positive re-screening results， were included in this study. Tandem mass spectrometry was employed to detect the level of acylcarnitine in dried blood spots. Neonates with positive primary screening results were recalled within 2 weeks， and further confirmation of SCADD was carried out through urine organic acid analysis， blood biochemistry tests， and gene detection. Results Among 113，367 newborns， 144 children tested positive in the primary screening， 20 were positive in the re-examination， and 7 were diagnosed with SCADD. The prevalence rate was 1/16，195. All 6 outpatient children with positive re-screening results were diagnosed with SCADD， resulting in a total of 13 confirmed cases. All patients showed no clinical symptoms. In 12 cases， blood butyryl-carnitine （C4）， the ratio of C4 to acetyl-carnitine （C2）， and the ratio of C4 to propionyl-carnitine （C3） were increased. In one case， C4 was normal， but the blood valeryl carnitine （C5）， the ratio of C5 to C2， and the ratio of C5 to C3 were increased. Urine organic acid detection revealed an increase in ethyl malonic acid in 8 cases， normal levels in 3 cases， and no detection in 2 cases. Among the 13 confirmed children， 2 were homozygous， and the rest were complex heterozygous. A total of 16 types of ACADS gene mutations were identified， including 15 known mutations and 1 unreported mutation. The known mutations were： c.989G > A， c.1031A > G， c.1165A > G， c.1054G > A， c.655G > A， c.981-983delGAC， c.974G > A， c.983C > A， c.682G > A， c.802C > G， c.46G > A， c.1192C > T， c.293A > G， c.625G > A， c.1195C > T. The unreported mutation was c.796-7C > A. The high-frequency mutation was c.1031A > G （46%）， and there was no significant correlation between the ACADS genotype and the levels of ethylmalonic acid or C4. After the newborns were diagnosed with SCADD， they were provided with dietary guidance， and L-carnitine and vitamin B2 were supplemented when necessary. During the follow-up period， no clinical symptoms emerged， and their physical and intellectual developments were normal. Conclusions The prevalence of SCADD in the Sichuan region was 1/16，195. A total of 16 mutation sites in the ACADS gene were detected. Children diagnosed with SCADD through neonatal screening exhibited no obvious clinical symptoms and had a good prognosis.
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