Mitochondrial complex I (CI) deficiencies (OMIM 252010) are the commonest inherited mitochondrial disorders in children. Acyl-CoA dehydrogenase 9 (ACAD9) is a flavoenzyme involved chiefly in CI assembly and possibly in fatty acid oxidation. Biallelic pathogenic variants result in CI dysfunction, with a phenotype ranging from early onset and sometimes fatal mitochondrial encephalopathy with lactic acidosis to late-onset exercise intolerance. Cardiomyopathy is often associated. We report a patient with childhood-onset optic and peripheral neuropathy without cardiac involvement, related to CI deficiency. Genetic analysis revealed compound heterozygous pathogenic variants in ACAD9, expanding the clinical spectrum associated to ACAD9 mutations. Importantly, riboflavin treatment (15 mg/kg/day) improved long-distance visual acuity and demonstrated significant rescue of CI activity in vitro.

线粒体复合体 I (CI) 缺陷 (OMIM 252010) 是儿童中最常见的遗传性线粒体疾病。酰基辅酶A 脱氢酶 9 (ACAD9) 是一种黄素酶，主要参与 CI 组装并可能参与脂肪酸氧化。双等位基因致病变异导致 CI​​ 功能障碍，其表型范围从早发性和有时致命的线粒体脑病伴乳酸酸中毒到迟发性运动不耐受。心肌病通常与之相关。我们报告了一名儿童期发病的视神经和周围神经病变，但没有心脏受累，与 CI 缺陷有关。遗传分析揭示了 ACAD9 中的复合杂合致病变异，扩大了与ACAD9相关的临床谱突变。重要的是，核黄素治疗（15 mg/kg/天）提高了远距离视力，并在体外证明了 CI 活性的显着拯救。