Mitochondrial Disorders Affecting the Nervous System

R.H. Haas, MB, BChir; Z. Zolkipli, MB, ChB


Semin Neurol. 2014;34(3):321-340. 

In This Article

Coenzyme Q10 Deficiency

Coenzyme Q10 (CoQ10) is an essential component of the ETC receiving electrons from complex I, complex II, electron transfer factor (fatty acid oxidation), and other substrates. It has many other functions including acting as both an antioxidant and a pro-oxidant, it is involved in the regulation of apoptosis and is a signaling molecule. Not surprisingly, synthetic defects cause mitochondrial disease and conversely mitochondrial disease causes CoQ10 deficiency.[182] Secondary CoQ10 deficiency is much more common than synthetic disease. Phenotypic variation is wide, but CoQ10 deficiency disorders often affect the brain and are particularly important to diagnose as they are treatable.[181] Steroid-resistant nephrotic syndrome with ataxia is seen with gene mutations in ADCK3 and ADCK4, which encode the aarF domain containing kinase 4 required for CoQ10 synthesis.[183] Other synthetic defects include mutations in COQ2, PDSS1, PDSS2, and COQ4, which cause infantile cytopathies with encephalopathy[184] and the COQ6 gene causing nephrotic syndrome with sensorineural deafness. Dominant cerebellar atrophy with ataxia and mitochondrial myopathy is another phenotype of these defects. Secondary CoQ10 deficiency with some response to treatment occurs in Friedreich ataxia.[185] Other disorders with secondary deficiency include the mtDNA depletion syndromes[186] electron transfer factor dehydrogenase gene defects producing the severe form of glutaric aciduria type II can also cause a late-onset mitochondrial myopathy.[187]