短链烯酰辅酶A水合酶1基因突变导致线粒体短链烯酰辅酶A水合酶1缺乏症1例

A case report of mitochondrial enoyl-CoA hydratase short chain 1 deficiency caused by enoyl-CoA hydratase short chain 1 gene mutation

目的:总结1例短链烯酰辅酶A水合酶1(ECHS1)基因导致线粒体短链烯酰辅酶A水合酶1缺乏症(ECHS1D)患儿的临床特征及基因突变特点。方法:回顾性分析2021年1月就诊于徐州市儿童医院神经内科的1例ECHS1D患儿的临床特点及基因检测结果,并通过检索国内外相关文献对该疾病的临床特征进行复习。结果:患儿男性,年龄6个月4 d,急性起病,临床以肢体活动障碍为主要表现。患儿运动发育迟缓,竖头尚可,不能翻身、独坐,不能追视,不能逗笑出声,四肢肌张力增高。入院检查示血乳酸水平升高至6.2 mmol/L,提示代谢性酸中毒。头颅磁共振成像(MRI)示双侧基底节区异常信号,左侧大脑半球脑膜异常强化。全外显子组测序发现该患儿ECHS1基因存在复合杂合突变,分别为c.563C>T(p.A188V)和c.5C>T(p.A2V),患儿父亲携带c.563C>T突变,母亲携带c.5C>T突变,均为错义突变。结论:ECHS1基因以错义突变为主,大部分为复合杂合突变,少部分为纯合突变。ECHS1基因突变导致线粒体ECHS1D常累及婴幼儿,发病相对较早,临床表现为代谢性酸中毒、运动发育迟缓、肌张力障碍等,头颅MRI可存在基底节区异常信号。对具有类似临床表现和MRI基底节异常信号的病例,应考虑基因检测明确诊断。

Objective To summarize the clinical features and gene mutation characteristics of a child with mitochondrial enoyl-CoA hydratase short chain 1 deficiency(ECHS1D)caused by enoyl-CoA hydratase short chain 1(ECHS1)gene mutation.Methods The clinical characteristics and genetic test results of a child with ECHS1D who visited the Department of Neurology of Xuzhou Children′s Hospital in January 2021 were retrospectively analyzed,and the clinical features of the disease were also reviewed by searching relevant domestic and foreign literature.Results The child was a 6 months and 4 days old male,with acute onset,the main clinical manifestation being limb movement disorder after admission.The child had slow motor development,his head was still upright and cannot turn over,the child also cannot sit alone,follow up and make a laugh,and the muscle tension of limbs was increased.The child′s blood lactate was increased to 6.2 mmol/L,which suggested metabolic acidosis,and magnetic resonance imaging(MRI)of the head showed abnormal signals in the basal ganglia on both sides,abnormal enhancement of the meninges of the left cerebral hemisphere.Whole exome sequencing revealed that the child had compound heterozygous mutations in ECHS1 gene,c.563C>T(p.A188V)and c.5C>T(p.A2V),respectively.The child′s father carried c.563C>T mutation,the mother carried c.5C>T mutation,all of which were missense mutations.Conclusions ECHS1 gene mainly has missense mutations,most of which are compound heterozygous mutations,and a few are homozygous mutations.The ECHS1D caused by ECHS1 gene mutation often affects infants and young children.MRI suggests abnormal signals in the basal ganglia;for cases with the above clinical manifestations and abnormal signals in the basal ganglia on MRI,genetic testing should be considered to confirm the diagnosis.