早发型极长链酰基辅酶A脱氢酶缺乏症3例临床及遗传学分析

Clinical and genetic analysis of early onset very long chain acyl-CoA dehydrogenase deficiency:a report of three cases

目的 探索早发型极长链酰基辅酶A脱氢酶缺乏症(VLCADD)的临床与遗传特征,提高对该疾病的认识。方法 回顾性分析2017年9月至2020年4月在上海交通大学医学院附属新华医院新生儿监护室诊治的3例早发型VLCADD患儿的基因型、临床表型及其预后情况。结果 3例经分子诊断的早发型VLCADD患儿中男2例,女1例,均无阳性家族史。3例患儿均在新生儿期以代谢危象或消化道症状起病。新生儿筛查2例C14:1增高,1例未行筛查。3例患儿均存在ACADVL基因变异,都为复合杂合子,变异来自父母,其中c. 1615 C> T、c. 231-232 insAATG未见报道。1例患儿生后母乳喂养,2日龄呼吸心跳骤停;另2例患儿因新生儿筛查异常,诊断后立即开始富含中链三酰甘油的特殊奶粉喂养,分别于3月龄、4月龄发生猝死。结论 早发型VLCADD为新生儿期、婴儿期潜在猝死性疾病之一,尽管积极开展早期诊断与治疗,但总体预后仍不佳,因此对先证者家系进行产前诊断、避免患儿出生至关重要。

Objective To explore the clinical features and genetic characteristics for early onset very long chain acyl-coenzyme A dehydrogenase deficiency(VLCADD)and to improve the understanding of this disease.Methods The genotypes,clinical phenotypes and prognosis of 3 neonates with early-onset VLCADD diagnosed and treated in the neonatal intensive care unit of Xinhua Hospital,Shanghai Jiao Tong University School of Medicine from September 2017 to April 2020 were retrospectively analyzed.Results Three children(2 boys and 1 girl)with early onset VLCADD were diagnosed by molecular method,and none of them had a positive family history.All three patients presented with metabolic crisis or digestive tract symptoms during the neonatal period.Two children were found to have increased C14:1 during the neonatal screening,and 1 case was not screened.All three children had ACADVL gene variations,which were complex heterozygotes,and the variations were from parents,among which c.1615 C>T and c.231-232 insAATG were not reported.One patient was breastfed after birth and had respiratory and cardiac arrest at 2 days of age.The other two children were fed special milk powder rich in medium-chain triacylglycerol immediately after the diagnosis due to abnormalities found in the neonatal screening,and sudden death occurred at 3 and 4 months of age,respectively.Conclusions Early onset VLCADD is one of the potential sudden death diseases in neonatal period and infancy.The prognosis is still poor despite early diagnosis and treatment.Therefore,prenatal diagnosis of fetuses from families with previous birth of VLCADD is an effective way to avoid the birth of early onset VLCADD children.