Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ₁₀)

Riboflavin and ubiquinone (Coenzyme Q₁₀, CoQ₁₀) deficiencies are heterogeneous groups of autosomal recessive conditions affecting both children and adults. Riboflavin (vitamin B₂)-derived cofactors are essential for the function of numerous dehydrogenases. Genetic defects of the riboflavin transport have been detected in Brown-Vialetto-Van Laere and Fazio-Londe syndromes (C20orf54), and haploinsufficiency of GPR172B has been proposed in one patient to cause persistent riboflavin deficiency. Mutations in the electron tranferring fravoprotein genes (ETFA/ETFB) and its dehydrogenase (ETFDH) are causative for multiple acyl-CoA dehydrogenase deficiency. Mutations in ACAD9, encoding the acyl-CoA dehydrogenase 9 protein were recently reported in mitochondrial disease with respiratory chain complex I deficiency. All these conditions may respond to riboflavin therapy. 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. The increasing number of molecular defects in enzymes of the CoQ₁₀ biosynthetic pathways (PDSS1, PDSS2, COQ2, COQ6, COQ9, CABC1/ADCK3) underlies the importance of these conditions. The clinical heterogeneity may reflect blocks at different levels in the complex biosynthetic pathway. Despite the identification of several primary CoQ₁₀ deficiency genes, the number of reported patients is still low, and no true genotype-phenotype correlations are known which makes the genetic diagnosis still difficult. Additionally to primary CoQ₁₀ deficiencies, where the mutation impairs a protein directly involved in CoQ₁₀ biosynthesis, we can differentiate secondary deficiencies. CoQ₁₀ supplementation may be beneficial in both primary and secondary deficiencies and therefore the early recognition of these diseases is of utmost importance.