A fatal case of -associated primary coenzyme Q deficiency.

BACKGROUND

Primary coenzyme Q (CoQ) deficiencies are clinically and genetically heterogeneous group of disorders associated with defects of genes involved in the CoQ biosynthesis pathway. -associated CoQ deficiency is very rare and only two cases have been reported.

METHODS AND RESULTS

We report a patient with encephalo-myo-nephro-cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Using whole exome sequencing, we identified compound heterozygous variants in the gene consisting of a deletion insertion resulting in frameshift [c.599_600delinsTAATGCATC, p.(Lys200Ilefs*56)] and a missense substitution [c.319C>T, p.(Arg107Trp), NM_016138.4]. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ level.

CONCLUSION

This third patient presenting with lethal encephalo-myo-nephro-cardiopathy represents the severe end of this ultra-rare mitochondrial disease caused by biallelic mutations. The response to CoQ supplement is poor and alternative treatment strategies should be developed for a more effective management of this disorder.