Mitochondrial DNA mutations and depletion in pediatric medicine

SummaryMitochondrial disorders are a group of diseases traditionally ascribed to defects of the respiratory chain, which is the only metabolic pathway in the cell that is under the control of the two separate genetic systems, the mitochondrial genome (mtDNA) and the nuclear genome (nDNA). Therefore the genetic classification of the primary mitochondrial diseases distinguishes disorders due to mutations in mtDNA, which are sporadic or maternal inherited, from disorders due to mutations in nDNA, which are governed by the stricter rules of mendelian genetics. Pathological alterations of mtDNA fall into two main categories: primary mutations of mitochondrial DNA (point mutations and rearrangements) and mtDNA perturbation, due to mutations in nuclear genes whose products are involved in mtDNA maintenance or replication. This article will focus on the primary mitochondrial DNA mutations and mtDNA depletion syndromes related to neonatal–infant human pathology.