Journal of Inherited Metabolic Disease

, Volume 32, Issue 2, pp 143–158

Clinical and molecular features of mitochondrial DNA depletion syndromes

  • A. Spinazzola
  • F. Invernizzi
  • F. Carrara
  • E. Lamantea
  • A. Donati
  • M. DiRocco
  • I. Giordano
  • M. Meznaric-Petrusa
  • E. Baruffini
  • I. Ferrero
  • M. Zeviani
SSIEM Symposium 2008

DOI: 10.1007/s10545-008-1038-z

Cite this article as:
Spinazzola, A., Invernizzi, F., Carrara, F. et al. J Inherit Metab Dis (2009) 32: 143. doi:10.1007/s10545-008-1038-z

Summary

Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-γA (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17). In this work, we review the MDS-associated phenotypes and present our own experience of 32 MDS patients, with the aim of defining the mutation frequency of the known genes, the clinical spectrum of the diseases, and the genotype–phenotype correlations. Five of our patients carried previously unreported mutations in one of the eight MDS genes.

Abbreviations

CK

creatine kinase

COX

cytochrome-c oxidase

MDS

mitochondrial DNA depletion syndrome

mtDNA

mitochondrial DNA

NAA

N-acetylaspartate

OXPHOS

oxidative phosphorylation

RC

respiratory chain

RRF

ragged-red fibres

SANDO

sensory ataxic neuropathy with dysarthria and ophthalmoplegia

SCAE

spinocerebellar ataxia-epilepsy syndrome

SCS

succinyl-CoA synthase

SDH

succinate dehydrogenase

SMA

spinal muscular atrophy

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • A. Spinazzola
    • 1
  • F. Invernizzi
    • 1
  • F. Carrara
    • 1
  • E. Lamantea
    • 1
  • A. Donati
    • 2
  • M. DiRocco
    • 3
  • I. Giordano
    • 4
  • M. Meznaric-Petrusa
    • 5
  • E. Baruffini
    • 6
  • I. Ferrero
    • 6
  • M. Zeviani
    • 1
  1. 1.Unit of Molecular NeurogeneticsIRCCS Foundation Neurological Institute ‘C. Besta’MilanItaly
  2. 2.Metabolic and Muscular UnitClinic of Pediatric Neurology, AOU MeyerFlorenceItaly
  3. 3.Pediatric IIInstitute ‘G. Gaslini’GenoaItaly
  4. 4.Department of Child and Adolescent NeuropsychiatrySpedali CiviliBresciaItaly
  5. 5.Medical Faculty, Institute of AnatomyUniversity of LjubljaniLjubljanaSlovenia
  6. 6.Department of Genetics, Biology of Microrganisms, Anthropology and EvolutionUniversity of ParmaParmaItaly