Objective: To determine the actual incidence of mitochondrial DNA (mtDNA) depletion syndrome in multiple respiratory chain deficiency.
Study design: We carried out a real-time polymerase chain reaction quantification of mtDNA in liver or muscle tissue of 100 children with unexplained multiple oxidative phosphorylation enzyme deficiency.
Results: A reduction of mtDNA copy number to <35% of control values was found in liver and/or muscle in half of the children (50/100). Most of these patients (32/50; 64%) presented with severe neonatal onset liver involvement; 7 (14%) had Alpers syndrome, and 11 (22%) exhibited various forms of neurologic involvement. Deoxyguanosine kinase or polymerase gamma (POLG) mutations could be identified in 11 of 32 patients with liver involvement, and POLG mutations were consistently found in all 7 patients with Alpers syndrome. Homozygous thymidine kinase 2 and MPV17 gene mutations were found in 2 patients.
Conclusions: Our findings show that mtDNA depletion is a prevalent cause of multiple respiratory chain deficiency in infancy.