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J Inherit Metab Dis. 2019 Jan 24. doi: 10.1002/jimd.12058. [Epub ahead of print]

Disorders of riboflavin metabolism.

Author information

1
Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
2
Kids Research Institute, The Children's Hospital at Westmead, Sydney, New South Wales, Australia.
3
Discipline of Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
4
Discipline of Child & Adolescent Health, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
5
Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
6
Department of Paediatrics, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia.
7
Mitochondrial Research Group, UCL Great Ormond Street Institute of Child Health, London, UK.
8
Metabolic Unit, Great Ormond Street Hospital NHS Foundation Trust, London, UK.

Abstract

Riboflavin (vitamin B2), a water-soluble vitamin, is an essential nutrient in higher organisms as it is not endogenously synthesised, with requirements being met principally by dietary intake. Tissue-specific 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 FLAD1 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.

KEYWORDS:

FLAD1 mutations; FAD synthase deficiency; flavocoenzyme; flavoprotein; flavoproteome; riboflavin metabolism; riboflavin responsive disorders; riboflavin transport

PMID:
30680745
DOI:
10.1002/jimd.12058

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