Metabolic Disorders Related to Riboflavin Transport and Deficiency

Riboflavin (vitamin B2) serves as the precursor for the essential cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which underpin mitochondrial oxidative phosphorylation, redox balance and a wide spectrum of flavoenzyme‐catalysed reactions. Intestinal and tissue uptake of riboflavin is mediated by specific transporter proteins encoded by SLC52A1, SLC52A2 and SLC52A3. Mutations in these genes lead to riboflavin transporter deficiency, a neurometabolic syndrome characterised by sensorineural hearing loss, cranial nerve dysfunction, motor neuropathy and respiratory compromise. At the cellular level, transporter defects and flavin scarcity impair electron transport chain complexes, provoke endoplasmic reticulum stress and activate intrinsic apoptotic pathways, particularly in motor neurons. Beyond inherited transporter disorders, suboptimal riboflavin status has been implicated in multiple acyl‐CoA dehydrogenase deficiency and other secondary mitochondrial myopathies, where flavin supplementation often restores enzyme stability, enhances residual activity and ameliorates clinical manifestations. Advances in genetic diagnostics, biochemical assays and in vitro disease models have deepened understanding of these disorders and guided the development of riboflavin‐based and cofactor‐targeted therapeutic strategies.

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Metabolic Disorders Related to Riboflavin Transport and Deficiency publication trend

The graph below shows the total number of articles in metabolic disorders related to riboflavin transport and deficiency across all publications each year (not limited to Nature Index journals).

Technical terms

Riboflavin transporter deficiency (RTD): A genetic disorder caused by mutations in riboflavin transporter genes leading to impaired cellular uptake of vitamin B2 and neurometabolic dysfunction.

Flavin mononucleotide (FMN): A phosphorylated form of riboflavin that functions as a cofactor in redox reactions and enzyme catalysis.

Flavin adenine dinucleotide (FAD): A riboflavin‐derived coenzyme essential for mitochondrial electron transport and energy metabolism.

Riboflavin kinase (RFK): An enzyme that catalyses the conversion of riboflavin to FMN, initiating the biosynthesis of flavin cofactors.

Flavoenzyme: An enzyme that requires FMN or FAD as a cofactor to perform oxidative or redox reactions.

Endoplasmic reticulum stress (ERS): A cellular response triggered by accumulation of misfolded proteins in the endoplasmic reticulum, often leading to apoptosis if unresolved.

References

1. Caspase-dependent apoptosis in Riboflavin Transporter Deficiency iPSCs and derived motor neurons. Cell Death Discovery (2024).
2. Neuroprotective effect of riboflavin kinase on cerebral ischemia injury in rats. Molecular Medicine (2025).
3. Clinical presentation and outcome of riboflavin transporter deficiency: mini review after five years of experience. Journal of Inherited Metabolic Disease (2016).
4. Remaining challenges in cellular flavin cofactor homeostasis and flavoprotein biogenesis. Frontiers in Chemistry (2015).
5. Riboflavin Deficiency—Implications for General Human Health and Inborn Errors of Metabolism. International Journal of Molecular Sciences (2020).