Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.
Division of Pediatric Neurology, Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Genomic Medicine, Rare Disease Center, Seoul National University Hospital, Seoul, Republic of Korea.
Neuromuscul Disord. 2021 Nov;31(11):1194-1198. doi: 10.1016/j.nmd.2021.07.006. Epub 2021 Jul 18.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is a heterogeneous group of inborn error of metabolic disease affecting the oxidation of fatty acids and amino acids, and choline metabolism. Genes involved in electrons transfer to the mitochondrial respiratory chain typically induce MADD. Recently, FLAD1, which encodes flavin adenine dinucleotide synthase, has also been reported as a cause of MADD. Here, we present a case of a 28-month girl with progressive weakness in facial and bulbar muscle. She has been suffering from feeding difficulty and recurrent respiratory distress. Lipid storage myopathy was evident from muscle biopsy. Furthermore, whole exome sequencing identified homozygous variant of c.745C > T (p.Arg249*) in FLAD1, confirming the diagnosis of FLAD1-related MADD. The patient showed improvements in her symptoms and exhibited catch-up growth following the supplementation of riboflavin. Lipid storage myopathy with FLAD1-related MADD is potentially treatable. Therefore, we should have high clinical suspicion, even though the diagnosis is challenging.
多种酰基辅酶 A 脱氢酶缺乏症(MADD)是一组异质性的代谢性疾病遗传缺陷,影响脂肪酸和氨基酸以及胆碱代谢的氧化。涉及电子向线粒体呼吸链转移的基因通常会导致 MADD。最近,编码黄素腺嘌呤二核苷酸合酶的 FLAD1 也被报道为 MADD 的病因之一。在此,我们报告了一例 28 个月大的女孩,她逐渐出现面部和球部肌肉无力。她一直存在喂养困难和反复呼吸窘迫。肌肉活检显示脂质贮积性肌病。此外,外显子组测序发现 FLAD1 中 c.745C>T(p.Arg249*)纯合变异,证实了 FLAD1 相关 MADD 的诊断。患者在补充核黄素后症状改善,并出现追赶性生长。FLAD1 相关 MADD 伴脂质贮积性肌病具有潜在的可治疗性。因此,即使诊断具有挑战性,我们也应高度怀疑这种疾病。