HADHB基因变异导致致死型线粒体三功能蛋白缺乏症1例

Lethal mitochondrial trifunctional protein deficiency caused by HADHB gene variation:a case report

本文报告了1例HADHB基因复合杂合变异导致的致死型线粒体三功能蛋白缺乏症(mitochondrial trifunctional protein deficiency,MTPD)。患儿生后24 h内起病,以“吃奶少伴心肌酶异常”为主诉在生后第4天转至南京医科大学附属儿童医院。入院时体格检查见精神稍萎靡,反应尚可,心肺腹无明显异常;实验室检查肌酸激酶同工酶及肌钙蛋白均偏高,心电图提示窦性心动过速、肢导联低电压;血液代谢筛查提示十四烯酰基肉碱及多种3-羟基肉碱均偏高;全外显子组测序结果示胎儿HADHB基因复合杂合变异[c.739C>T(p.Arg247Cys)和c.607C>T(p.Arg203Ter,272)]。随访至3月龄,患儿受凉后出现吃奶差、精神差,再入院后出现心力衰竭、呼吸衰竭等多脏器功能障碍表现,经治疗无效后死亡。致死型MTPD较为罕见,目前无有效治疗措施,预后差。对于新生儿期出现不明原因心肌病、低血糖、酸中毒等代谢异常表现,应警惕致死型MTPD可能,新生儿期基因检测可早期明确诊断。

This article reported a male neonate with lethal mitochondrial trifunctional protein deficiency(MTPD)caused by compound heterozygous variations in the HADHB gene.The patient presented with poor milk intake complicated by abnormal myocardial enzymes within 24 h after birth and was transferred to the Children's Hospital of Nanjing Medical University on day 4.Physical examination revealed no obvious abnormalities on admission.Laboratory examination showed increased creatine kinase isoenzyme and cardiac troponin levels,and electrocardiogram suggested sinus tachycardia and low QRS voltage in limb leads.Blood screening for metabolic abnormalities showed high levels of tetradecenyl carnitine and various 3-hydroxycarnitines.Heterozygous mutations of c.739C>T(p.Arg247Cys)and c.607C>T(p.Arg203Ter,272)were detected in the HADHB gene in the boy,which were pathogenic variants included in the Human Gene Mutation Database.Followed up to three months of age,the boy was readmitted to hospital due to poor milk intake for one week and poor response for 2 d after catching a cold.After admission,he quickly developed multiple organs dysfunction such as heart failure and respiratory failure,and then died.Lethal MTPD is rare with no effective treatment and poor prognosis.Lethal MTPD should be highly suspected when unexplained cardiomyopathy,hypoglycemia,acidosis and other metabolic abnormalities appear in the neonatal period,and an early diagnosis could be confirmed with genetic testing in the neonatal period.