M.I.4 Primary and secondary coenzyme Q10 deficiency

Abstract

Coenzyme Q10 (CoQ10) is a lipid-soluble component of virtually all cell membranes and has multiple metabolic functions including the transport of electrons from mitochondrial respiratory chain complexes I and II to complex III. Deficiency of CoQ10 is an autosomal recessive syndrome with four major phenotypes: (1) encephalomyopathy characterized by the triad of recurrent myoglobinuria, brain involvement and ragged-red fibers; (2) severe infantile multisystemic disease; (3) cerebellar ataxia; and (4) isolated myopathy. The diversity of clinical presentations of CoQ10 deficiency suggests etiological heterogeneity, which has, in fact, been demonstrated by the identification of mutations in multiple genes. Mutations in the CoQ10 biosynthetic genes, PDSS1, PDSS2, and COQ2 have been identified in four families with infantile-onset disorders, predominantly encephalomyopathies with nephrotic syndrome. In addition, CoQ10 deficiency can be secondary as demonstrated by the association of APTX mutations, which cause ataxia oculomotor apraxia (AOA1) with deficiency of CoQ10 while mutations in electron-transferring flavoprotein dehydrogenase (ETF-DH) have been identified with the pure myopathic form of CoQ10 deficiency. Deficiency of CoQ10 is best detected in muscle biopsies or cultured fibroblasts, but blood levels of CoQ10 are not reliable to diagnose this condition. Defects of mitochondrial respiratory chain enzyme complexes I + III and II + III with normal activities of the individual enzymes is a clue to diagnose CoQ10 deficiency. Patients with all forms of CoQ10 deficiency have shown clinical improvements after initiating oral CoQ10 supplementation. Thus, early diagnosis is of critical importance in the management of these patients.