电子转移黄素蛋白脱氢酶基因突变所致的核黄素反应性脂质沉积性肌病的临床、病理和基因特征分析

Clinical, pathological, and genetic features of riboflavin responsive multiple acyl-CoA dehydrogenation deficiency caused by electron transfer flavoprotein dehydrogenase mutation

摘要:

目的 分析电子转移黄素蛋白脱氢酶（ETFDH）突变所致的核黄素反应性脂质沉积性肌病（RR-MADD）的临床特点、肌肉病理以及血、尿质谱筛查结果和基因突变特点，旨在为早期诊断和治疗提供帮助。方法 回顾性分析该院2009年至2019年确诊的15例ETFDH突变所致的脂质沉积性肌病患者的各项资料。结果 15例患者平均发病年龄为（32.1±13.6）岁，均以肢体无力为首发症状，其中四肢起病者占53.3%，双下肢起病者占46.7%。所有患者的肌酶水平均升高；肌电图结果提示80%呈肌源性损害，13.3%为肌源性合并神经源性损害，6.7%结果正常。血、尿质谱的阳性检出率分别为66.7%和22.2%；基因检测提示所有患者存在ETFDH基因不同位点突变，其中单一杂合突变和复合杂合突变各占40%，纯合突变占20%。结论 该病以波动性肌无力伴肌酶升高为主要表现，患者应尽快行肌肉病理检查，同时联合血、尿代谢筛查和基因检测有助于RR-MADD患者早期诊断和及时治疗。

Abstract:

Objective To investigate the clinical features, muscle pathological changes, blood and urine screening by mass spectrometry, and gene mutations of riboflavin responsive multiple acyl-CoA dehydrogenation deficiency (RR-MADD) caused by electron transfer flavoprotein dehydrogenase (ETFDH) mutation, and to provide help for early diagnosis and treatment. Methods A retrospective analysis was performed for related data of 15 patients with RR-MADD caused by ETFDH mutation who were diagnosed in our hospital from 2009 to 2019. Results The 15 patients had a mean age of onset of 32.1±13.6 years and had the initial symptom of limb weakness, among whom 53.3% had weakness in all extremities and 46.7% had weakness in both lower limbs. All patients had increases in muscle enzymes, and electromyography showed myogenic damage in 80% of the patients, myogenic and neurogenic damage in 13.3% of the patients, and normal results in 6.7% of the patients. The positive rates of blood and urine mass spectrometry were 66.7% and 22.2%, respectively. Gene detection showed that all patients had mutations at different loci of the ETFDH gene, among whom 40% had single heterozygous mutations, 40% had compound heterozygous mutations, and 20% had homozygous mutations. Conclusions This disease mainly manifests as fluctuating muscle weakness and elevated muscle enzymes. Muscle pathological examination should be performed for such patients as soon as possible, and a combination of blood and urine metabolic screening and gene detection may help with early diagnosis and timely treatment of such patients.