Journal of Neurology

, Volume 242, Issue 9, pp 547–556 | Cite as

Early-onset encephalomyopathy associated with tissue-specific mitochondrial DNA depletion: A morphological, biochemical and molecular-genetic study

  • Caterina Mariotti
  • Graziella Uziel
  • Franco Carrara
  • Marina Mora
  • Alessandro Prelle
  • Valeria Tiranti
  • Stefano DiDonato
  • Massimo Zeviani
Original Communication


A male infant, born from consanguineous parents, suffered from birth with a progressive neuromuscular disorder characterized by psychomotor delay, hypotonia, muscle weakness and wasting, deep-tendon areflexia and spastic posture. High levels of lactic acid in blood and cerebrospinal fluid suggested a mitochondrial respiratory chain defect. Muscle biopsy revealed raggedred and cytochromec oxidase-negative fibres, lipid accumulation and dystrophic changes. Multiple defects of respiratory complexes were detected in muscle homogenate, but cultured fibroblasts, myoblasts and myotubes were normal. Southern blot analysis showed markedly reduced levels of mitochondrial DNA (mtDNA) in muscle, while lymphocytes, fibroblasts and muscle precursor cells were normal. Neither depletion of mtDNA nor abnormalities of the respiratory complexes were observed in innervated muscle fibres cultured for as long as 4 months. No mutations were observed in two candidate nuclear genes,mtTFA andmtSSB, retro-transcribed, amplified and sequenced from the proband's mRNA. Sequence analysis of the mtDNA D-loop and of the origin of replication of the mtDNA light strand failed to identify potentially pathogenic mutations of these replicative elements in the proband's muscle mtDNA. Our findings indicate that mtDNA depletion is due to a nuclear encoded gene and suggest that the abnormality underlying defective mtDNA propagation must occur after muscle differentiation in vivo.

Key words

Early-onset encephalomyopathy Mitochondrial DNA depletion 


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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Caterina Mariotti
    • 1
  • Graziella Uziel
    • 2
  • Franco Carrara
    • 1
  • Marina Mora
    • 3
  • Alessandro Prelle
    • 4
  • Valeria Tiranti
    • 1
  • Stefano DiDonato
    • 1
  • Massimo Zeviani
    • 1
  1. 1.Division of Biochemistry and GeneticsNational Neurological Institute “Carlo Besta”MilanItaly
  2. 2.Division of Child NeurologyNational Neurological Institute “Carlo Besta”MilanItaly
  3. 3.Division of Muscle PathologyNational Neurological Institute “Carlo Besta”MilanItaly
  4. 4.Institute of Clinical NeurologyUniversita StataleMilanItaly

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