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

Research output: Contribution to journalArticle


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 cytochrome c 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 and mtSSB, 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.

Original languageEnglish
Pages (from-to)547-556
Number of pages10
JournalJournal of Neurology
Issue number9
Publication statusPublished - Sep 1995



  • Early-onset encephalomyopathy
  • Mitochondrial DNA depletion

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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