ETFDH and mitochondrial disease: Consequently, riboflavin supplementation may improve symptoms and the clinical course of subjects affected by multiple acyl-CoA dehydrogenase deficiency (typically caused by electron-transport flavoprotein dehydrogenase (ETFDH) gene mutations) [40], mitochondrial diseases with complexes I and II deficiencies (as reported by some non-randomized studies in the literature) [50,51], and acyl-CoA dehydrogenase-9 (ACAD9) deficiency (which results in increased complex I activity in fibroblasts of patients).