PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
未经证实：脂质贮积肌病（LSM）是一种常染色体隐性遗传的脂质和氨基酸代谢紊乱，具有很大的临床异质性。电子转移黄素蛋白脱氢酶（ETFDH）基因的变异导致多种酰基辅酶A脱氢酶缺乏症（MADD），并有LSM的表现。肌肉活检有助于明确LSM的诊断，和下一代测序（NGS）可用于识别基因组突变位点。MADD的诊断有助于靶向治疗。
未经评估：我们报道了一名青少年，他在发病时出现肌肉无力和运动不耐受。在转诊到我们医院之前，他因疑似多发性肌炎而接受糖皮质激素治疗失败.先证者和他父母的下一代测序揭示了杂合变异，c.365G>A（p。G122D)继承自父亲，c.176-194_176-193del，和c.832-316C>T遗传自母亲的ETFDH基因。串联质谱鉴定突变为致病性的。然而,他的父母和他的妹妹被检测出突变c.365G>A没有临床症状。这表明ETFDH中三种复合杂合突变的组合是显著的。MADD被诊断出来后,一个戏剧性的临床恢复和生化改善表现为核黄素给病人一个星期，进一步证实了MADD的诊断。
UNASSIGNED：我们的观察扩展了中国人群中ETFDH变异的范围，并加强了NGS在MADD诊断中的作用。LSM的早期诊断和适当治疗可带来巨大的临床疗效，并避免一些致命的并发症。
未经评估：我们报道了一名青少年，他在发病时出现肌肉无力和运动不耐受。在转诊到我们医院之前，他因疑似多发性肌炎而接受糖皮质激素治疗失败.先证者和他父母的下一代测序揭示了杂合变异，c.365G>A（p。G122D)继承自父亲，c.176-194_176-193del，和c.832-316C>T遗传自母亲的ETFDH基因。串联质谱鉴定突变为致病性的。然而,他的父母和他的妹妹被检测出突变c.365G>A没有临床症状。这表明ETFDH中三种复合杂合突变的组合是显著的。MADD被诊断出来后,一个戏剧性的临床恢复和生化改善表现为核黄素给病人一个星期，进一步证实了MADD的诊断。
UNASSIGNED：我们的观察扩展了中国人群中ETFDH变异的范围，并加强了NGS在MADD诊断中的作用。LSM的早期诊断和适当治疗可带来巨大的临床疗效，并避免一些致命的并发症。
