A fatal case of COQ7-associated primary coenzyme Q10 deficiency

• Published in: JIMD reports Vol. 47; no. 1; pp. 23 - 29
• Main Authors: Kwong, Anna K-Y, Chiu, Annie T-G, Tsang, Mandy H-Y, Lun, Kin-Shing, Rodenburg, Richard J T, Smeitink, Jan, Chung, Brian H-Y, Fung, Cheuk-Wing
• Format: Report
• Language: English
• Published: 01.05.2019
• ISSN: 2192-8304
• DOI: 10.1002/jmd2.12032

BACKGROUNDPrimary coenzyme Q10 (CoQ10) deficiencies are clinically and genetically heterogeneous group of disorders associated with defects of genes involved in the CoQ10 biosynthesis pathway. COQ7-associated CoQ10 deficiency is very rare and only two cases have been reported. METHODS AND RESULTSWe 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 COQ7 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 CoQ10 level. CONCLUSIONThis third patient presenting with lethal encephalo-myo-nephro-cardiopathy represents the severe end of this ultra-rare mitochondrial disease caused by biallelic COQ7 mutations. The response to CoQ10 supplement is poor and alternative treatment strategies should be developed for a more effective management of this disorder.