Human CoQ 10 deficiencies

Coenzyme Q 10 (CoQ 10 or ubiquinone) is a lipid‐soluble component of virtually all cell membranes and has multiple metabolic functions. A major function of CoQ 10 is to transport electrons from complexes I and II to complex III in the respiratory chain which resides in the mitochondrial inner membrane. Deficiencies of CoQ 10 (MIM 607426) have been associated with four major clinical phenotypes: 1) encephalomyopathy characterized by a triad of recurrent myoglobinuria, brain involvement, and ragged‐red fibers; 2) infantile multisystemic disease typically with prominent nephropathy and encephalopathy; 3) cerebellar ataxia with marked cerebellar atrophy; and 4) pure myopathy. Primary CoQ 10 deficiencies due to mutations in ubiquinone biosynthetic genes ( COQ2 , PDSS1 , PDSS2 , and ADCK3 [ CABC1 ]) have been identified in patients with the infantile multisystemic and cerebellar ataxic phenotypes. In contrast, secondary CoQ 10 deficiencies, due to mutations in genes not directly related to ubiquinone biosynthesis ( APTX , ETFDH , and BRAF ), have been identified in patients with cerebellar ataxia, pure myopathy, and cardiofaciocutaneous syndrome. In many patients with CoQ 10 deficiencies, the causative molecular genetic defects remain unknown; therefore, it is likely that mutations in additional genes will be identified as causes of CoQ 10 deficiencies.