Coenzyme Q(10) is a remarkable
lipid involved in many cellular processes such as energy production through the mitochondrial respiratory chain (RC), beta-oxidation of
fatty acids, and
pyrimidine biosynthesis, but it is also one of the main cellular
antioxidants. Its biosynthesis is still incompletely characterized and requires at least 15 genes. Mutations in eight of them (PDSS1, PDSS2, COQ2, COQ4,
COQ6, ADCK3, ADCK4, and
COQ9) cause primary
CoQ(10) deficiency, a heterogeneous group of disorders with variable age of onset (from birth to the seventh decade) and associated clinical phenotypes, ranging from a fatal multisystem disease to isolated
steroid resistant nephrotic syndrome (SRNS) or isolated
central nervous system disease. The pathogenesis is complex and related to the different functions of
CoQ(10). It involves defective
ATP production and oxidative stress, but also an impairment of
pyrimidine biosynthesis and increased apoptosis.
CoQ(10) deficiency can also be observed in patients with defects unrelated to
CoQ(10) biosynthesis, such as RC defects,
multiple acyl-CoA dehydrogenase deficiency, and
ataxia and oculomotor
apraxia.Patients with both primary and secondary deficiencies benefit from high-dose oral supplementation with
CoQ(10). In primary forms treatment can stop the progression of both SRNS and
encephalopathy, hence the critical importance of a prompt diagnosis. Treatment may be beneficial also for secondary forms, although with less striking results.In this review we will focus on
CoQ(10) biosynthesis in humans, on the genetic defects and the specific clinical phenotypes associated with
CoQ(10) deficiency, and on the diagnostic strategies for these conditions.