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Tissue\u2010specific transporter proteins direct riboflavin to the intracellular machinery responsible for the biosynthesis of the flavocoenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These flavocoenzymes play a vital role in ensuring the functionality of a multitude of flavoproteins involved in bioenergetics, redox homeostasis, DNA repair, chromatin remodelling, protein folding, apoptosis, and other physiologically relevant processes. Hence, it is not surprising that the impairment of flavin homeostasis in humans may lead to multisystem dysfunction including neuromuscular disorders, anaemia, abnormal fetal development, and cardiovascular disease. In this review, we provide an overview of riboflavin absorption, transport, and metabolism. We then focus on the clinical and biochemical features associated with biallelic <jats:italic>FLAD1<\/jats:italic> mutations leading to FAD synthase deficiency, the only known primary defect in flavocoenzyme synthesis, in addition to providing an overview of clinical disorders associated with nutritional deficiency of riboflavin and primary defects of riboflavin transport. Finally, we give a brief overview of disorders of the cellular flavoproteome. Because riboflavin therapy may be beneficial in a number of primary or secondary disorders of the cellular flavoproteome, early recognition and prompt management of these disorders is imperative.<\/jats:p>","DOI":"10.1002\/jimd.12058","type":"journal-article","created":{"date-parts":[[2019,1,25]],"date-time":"2019-01-25T03:42:13Z","timestamp":1548387733000},"page":"608-619","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":162,"title":["Disorders of riboflavin metabolism"],"prefix":"10.1002","volume":"42","author":[{"given":"Shanti","family":"Balasubramaniam","sequence":"first","affiliation":[{"name":"Western Sydney Genetics Program The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Kids Research Institute The Children's Hospital at Westmead  Sydney New South Wales Australia"},{"name":"Discipline of Genetic Medicine, Sydney Medical School University of Sydney  Sydney New South Wales 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