Tian Huihong, Zhong Yi, Liu Zhihua, Wei Liping, Yuan Yanbo, Zhang Yuhu, Wang Limin
Department of Neurology, Guangdong Provincial People's Hospital, Guangdong Neuroscience Institute, Guangdong Academy of Medical Sciences, Guangzhou, China.
Shantou University Medical College, Shantou, China.
Front Neurol. 2022 Dec 15;13:991060. doi: 10.3389/fneur.2022.991060. eCollection 2022.
Lipid storage myopathy (LSM) is an autosomal recessive inherited lipid and amino metabolic disorder with great clinical heterogeneity. Variations in the electron transfer flavoprotein dehydrogenase (ETFDH) gene cause multiple acyl-CoA dehydrogenase deficiency (MADD), and have a manifestation of LSM. Muscle biopsy helps clarify the diagnosis of LSM, and next-generation sequencing (NGS) can be useful in identifying genomic mutation sites. The diagnosis of MADD contributes to targeted therapy.
We report on a teenager who appeared to have muscle weakness and exercise intolerance at the onset. Before the referral to our hospital, he was unsuccessfully treated with glucocorticoid for suspected polymyositis. The next-generation sequencing of the proband and his parents revealed heterozygous variations, c.365G>A (p.G122D) inherited from the father, c.176-194_176-193del, and c.832-316C>T inherited from the mother in the ETFDH gene. The tandem mass spectrometry identified the mutations to be pathogenic. However, his parents and his younger sister who were detected with a mutation of c.365G>A presented no clinical symptoms. This indicates that the combination of the three compound heterozygous mutations in ETFDH is significant. After MADD was diagnosed, a dramatic clinical recovery and biochemical improvement presented as riboflavin was given to the patient across a week, which further confirmed the diagnosis of MADD.
Our observations extend the spectrum of ETFDH variants in Chinese the population and reinforce the role of NGS in diagnosis of MADD. Early diagnosis and appropriate treatment of LSM lead to great clinical efficacy and avoid some lethal complications.
脂质贮积性肌病（LSM）是一种常染色体隐性遗传的脂质和氨基酸代谢紊乱疾病，具有高度的临床异质性。电子传递黄素蛋白脱氢酶（ETFDH）基因的变异会导致多种酰基辅酶A脱氢酶缺乏症（MADD），并表现为LSM。肌肉活检有助于明确LSM的诊断，而二代测序（NGS）可用于识别基因组突变位点。MADD的诊断有助于进行针对性治疗。
我们报告一名青少年，起病时表现为肌无力和运动不耐受。在转诊至我院之前，他因疑似多发性肌炎接受糖皮质激素治疗但效果不佳。对先证者及其父母进行二代测序，发现ETFDH基因存在杂合变异，c.365G>A（p.G122D）来自父亲，c.176 - 194_176 - 193del和c.832 - 316C>T来自母亲。串联质谱分析确定这些突变为致病性突变。然而，其父母及检测到c.365G>A突变的妹妹均无临床症状。这表明ETFDH基因中这三个复合杂合突变的组合具有重要意义。诊断为MADD后，患者在一周内接受核黄素治疗，临床症状显著改善，生化指标也有所改善，这进一步证实了MADD的诊断。
我们的观察结果扩展了中国人群中ETFDH变异的范围，并强化了NGS在MADD诊断中的作用。LSM的早期诊断和恰当治疗可带来良好的临床疗效，并避免一些致命并发症。
