Abstract
Riboflavin, or vitamin B2, is the precursor of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are essential cofactors of numerous dehydrogenases. The most common form of riboflavin disorder is its deficiency due to insufficient dietary intake. Riboflavin-responsive inborn errors of metabolism were shown to be due to the riboflavin chaperone-like function, which stabilises mutant FAD-containing dehydrogenases, most often ETFDH. Recessive mutations of SLC52A2 and SLC52A3 encoding the human riboflavin transporters RFVT2 and RFVT3 are cause Brown-Vialetto-Van Laere and Fazio-Londe syndromes, while haploinsufficiency of SLC52A1 has been proposed to cause persistent riboflavin deficiency.
Ubiquinone (coenzyme Q10, CoQ10) is a lipid-soluble component of the cell membranes, where it functions as a mobile electron and proton carrier but also participates in other cellular processes as a potent antioxidant and by influencing pyrimidine metabolism. Five major clinical phenotypes of CoQ10 deficiency have been described (encephalomyopathy, multisystem infantile variant, cerebellar form, Leigh syndrome, isolated myopathy) before the identification of disease genes. An increasing number of molecular defects in the CoQ10 biosynthetic pathways have been identified in different clinical variants (PDSS1, PDSS2, COQ2, COQ6, COQ9, CABC1/ADCK3). Despite this, the number of reported patients is still low, and the absence of clear genotype-phenotype correlations makes the genetic diagnosis challenging. In addition to primary CoQ10 deficiencies, where the mutation impairs a protein directly involved in CoQ10 biosynthesis, secondary CoQ10 deficiencies include disease not due to deficient synthesis of CoQ10 but associated with decreased CoQ10 levels, which may be contributing to the clinical symptoms.
Because of the beneficial effect of CoQ10 and riboflavin supplementation, early recognition of riboflavin and CoQ10 diseases is important.
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Horvath, R., Lombès, A. (2014). Riboflavin and CoQ Disorders. In: Blau, N., Duran, M., Gibson, K., Dionisi Vici, C. (eds) Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-40337-8_16
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DOI: https://doi.org/10.1007/978-3-642-40337-8_16
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