Journal of Inherited Metabolic Disease

, Volume 19, Issue 4, pp 504–520 | Cite as

Neurological presentations of mitochondrial diseases

  • M. Zeviani
  • B. Bertagnolio
  • G. Uziel


We present here a report on a 5-year experience in clinical investigation, diagnostic management and molecular genetic studies of neuromitochondrial disorders, defined on the basis of morphological, biochemical and genetic findings. Leigh disease is the most frequent clinical presentation in infancy and childhood, but symptoms at onset are poorly informative. In paediatric cases, lactic acidosis and neuroradiological abnormalities are frequent, and can be of help for the diagnostic orientation. In the adult population, muscle weakness, ophthalmoplegia with ragged-red fibres, retinitis pigmentosa, progressive myoclonal ataxia, and early-onset stroke-like episodes, are frequently combined in complex syndromes that are often familial (maternally inherited) and/or associated with well-established mutations in mitochondrial DNA (mtDNA). However, the presence of overlap syndromes and features common to many neuromitochondrial diseases can complicate the clinical evaluation and the diagnostic approach. The pathogenicity of a given mtDNA mutation can frequently be ascertained by correlating the degree of heteroplasmy with the clinical or biochemical phenotypes. Moreover, transmitochondrial cybrids can be used to test the effects of either mitochondrial or nuclear gene abnormalities in a fully controlled, user-friendly and highly informative system.


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Copyright information

© SSIEM and Kluwer Academic Publishers 1996

Authors and Affiliations

  • M. Zeviani
    • 2
  • B. Bertagnolio
    • 2
  • G. Uziel
    • 1
  1. 1.Division of Child NeurologyIstituto Nazionale Neurologico ‘C. Besta’MilanItaly
  2. 2.Division of Biochemistry & GeneticsNational Neurological Institute ‘Carlo Besta’MilanoItaly

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