Riboflavin and
ubiquinone (
Coenzyme Q(10),
CoQ(10)) deficiencies are heterogeneous groups of autosomal recessive conditions affecting both children and adults.
Riboflavin (vitamin B(2))-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.
CoQ(10) 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
CoQ(10) 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
CoQ(10) 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
CoQ(10) deficiencies, where the mutation impairs a
protein directly involved in
CoQ(10) biosynthesis, we can differentiate secondary deficiencies.
CoQ(10) supplementation may be beneficial in both primary and secondary deficiencies and therefore the early recognition of these diseases is of utmost importance.