This secondary mtDNA defect is expressed in one of two forms: mtDNA depletion syndromes are characterised by a quantitative loss of mtDNA copy number, leading to isolated organ or multi-systemic paediatric disease, and have been described in association with recessive mutations in at least nine genes – POLG, PEO1, DGUOK, TK2, RRM2B, TYMP, MPV17, SUCLA2 and SUCLG1[3]. This evidence concerns the gene TWNK and mitochondrial DNA depletion syndrome.