Mitochondrial DNA depletion syndrome: new descriptions and the use of citrate synthase as a helpful tool to better characterise the patients

Mol Genet Metab. 2012 Nov;107(3):409-15. doi: 10.1016/j.ymgme.2012.08.018. Epub 2012 Aug 31.


Mitochondrial DNA depletion syndrome (MDS) is a clinically heterogeneous group of mitochondrial disorders characterised by a quantitative reduction of the mitochondrial DNA copy number. Three main clinical forms of MDS: myopathic, encephalomyopathic and hepatocerebral have been defined, although patients may present with other MDS associated clinical symptoms and signs that cover a wide spectrum of onset age and disease. We studied 52 paediatric individuals suspected to have MDS. These patients have been divided into three different groups, and the appropriate MDS genes have been screened according to their clinical and biochemical phenotypes. Mutational study of DGUOK, MPV17, SUCLA2, SUCLG1 and POLG allowed us to identify 3 novel mutations (c.1048G>A and c.1049G>T in SUCLA2 and c.531+4A>T in SUCLG1) and 7 already known mutations in 10 patients (8 families). Seventeen patients presented with mtDNA depletion in liver or muscle, but the cause of mtDNA depletion still remains unknown in 8 of them. When possible, we quantified mtDNA/nDNA and CS activity in the same tissue sample, providing an additional tool for the study of MDS. The ratio (mtDNA/nDNA)/CS has shed some light in the discrepant results between the mtDNA copy number and the enzymatic respiratory chain activities of some cases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Citrate (si)-Synthase / genetics
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • DNA Polymerase gamma
  • DNA, Mitochondrial / genetics
  • DNA-Directed DNA Polymerase / genetics
  • Diffuse Cerebral Sclerosis of Schilder / diagnosis
  • Diffuse Cerebral Sclerosis of Schilder / enzymology
  • Diffuse Cerebral Sclerosis of Schilder / genetics
  • Female
  • Humans
  • Male
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / enzymology
  • Metabolism, Inborn Errors / genetics*
  • Mitochondria / enzymology
  • Mitochondria / genetics
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Myopathies / diagnosis
  • Mitochondrial Myopathies / enzymology
  • Mitochondrial Myopathies / genetics*
  • Muscular Diseases / diagnosis
  • Muscular Diseases / enzymology
  • Muscular Diseases / genetics*
  • Mutation
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Succinate-CoA Ligases / genetics*
  • Young Adult


  • DNA, Mitochondrial
  • Citrate (si)-Synthase
  • Phosphotransferases (Alcohol Group Acceptor)
  • deoxyguanosine kinase
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human
  • Succinate-CoA Ligases
  • SUCLA2 protein, human

Supplementary concepts

  • Mitochondrial DNA Depletion Syndrome, Hepatocerebral Form, Autosomal Recessive
  • Mitochondrial DNA Depletion Syndrome, Myopathic Form
  • Mitochondrial Dna Depletion Syndrome, Encephalomyopathic Form, With Methylmalonic Aciduria, Autosomal Recessive