Harel-Yoon综合征一家系临床表型及ATAD3A基因变异分析

ATAD3A gene variations in a family with Harel-Yoon syndrome

一例11 d女性新生儿因咳嗽伴口吐白沫、喂养困难就诊。实验室检查结果提示高乳酸血症,心肌损伤标志物升高,炎症指标升高,血串联质谱酰基肉碱检测辛酰基肉碱、癸酰基肉碱偏高。心脏超声及磁共振提示心功能不全、肥厚型心肌病。进一步完善家系全外显子测序,结果显示先证者及其姐姐均为ATAD3A基因c.1492dup(p.T498Nfs*13)和c.1376T>C(p.F459S)复合杂合变异,分别遗传自其父亲和母亲,诊断为Harel-Yoon综合征。先证者及其姐姐出生后均出现代谢性酸中毒、高乳酸血症、喂养困难、心肌损伤标志物升高、心功能不全等临床表现,均在婴儿早期死亡。

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties.The laboratory results indicated hyperlactatemia,elevated markers of myocardial injury and inflammation,and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry.Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy.Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup(p.T498Nfs*13)and c.1376T>C(p.F459S)in the ATAD3A gene,inherited from their father and mother,respectively.The diagnosis of Harel-Yoon syndrome was confirmed.The proband and her sister were born with clinical manifestations of metabolic acidosis,hyperlactatemia,feeding difficulties,elevated markers of myocardial injury as well as cardiac insufficiency,and both died in early infancy.