PDF(Pubmed)
Abstract：
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare autosomal recessive long-chain fatty acid oxidation disorder caused by mutations in the ACADVL gene. The myopathic form presents with exercise intolerance, exercise-related rhabdomyolysis, and muscle pain, usually starting during adolescence or adulthood. We report on a 17-year-old boy who has presented with exercise-induced muscle pain and fatigue since childhood. In recent clinical history, episodes of exercise-related severe hyperCKemia and myoglobinuria were reported. Electromyography was normal, and a muscle biopsy showed only \"moth-eaten\" fibers, and a mild increase in lipid storage in muscle fibers. NGS analysis displayed the already known heterozygote c.1769G>A variant and the unreported heterozygote c.523G>C change in ACADVL both having disease-causing predictions. Plasma acylcarnitine profiles revealed high long-chain acylcarnitine species levels, especially C14:1. Clinical, histopathological, biochemical, and genetic tests supported the diagnosis of VLCAD deficiency. Our report of a novel pathogenic missense variant in ACADVL expands the allelic heterogeneity of the disease. Since dietary treatment is the only therapy available for treating VLCAD deficiency and it is more useful the earlier it is started, prompt diagnosis is essential in order to minimize muscle damage and slow the disease progression.
摘要：
超长链酰基辅酶A脱氢酶（VLCAD）缺乏症是一种罕见的常染色体隐性遗传长链脂肪酸氧化障碍，由ACADVL基因突变引起。肌病形式表现为运动不耐受，运动相关横纹肌溶解症,肌肉疼痛,通常在青春期或成年期开始。我们报道了一个17岁的男孩，他从小就表现出运动引起的肌肉疼痛和疲劳。在最近的临床历史中，报告了运动相关的严重高CKA血症和肌红蛋白尿的发作.肌电图正常,肌肉活检显示只有“蛾食”纤维，肌肉纤维中的脂质储存略有增加。NGS分析显示ACADVL中已知的杂合子c.1769G>A变体和未报道的杂合子c.523G>C变化均具有致病预测。血浆酰基肉碱谱显示出较高的长链酰基肉碱种类水平，尤其是C14:1.临床,组织病理学,生物化学，基因测试支持VLCAD缺乏症的诊断。我们关于ACADVL中一种新的致病性错义变异的报道扩大了该疾病的等位基因异质性。由于饮食治疗是唯一可用于治疗VLCAD缺乏症的疗法，并且开始越早，它就越有用，及时诊断对于减少肌肉损伤和减缓疾病进展至关重要。
