Advertisement

Acta Neuropathologica

, Volume 110, Issue 2, pp 199–202 | Cite as

Unusual features of mitochondrial degeneration in skeletal muscle of patients with nuclear complex I mutation

  • Argirios DinopoulosEmail author
  • Jan Smeitink
  • Henk ter Laak
Letter to the Editor

We examined the histopathological finding in muscle of four patients with known nuclear mutations of complex I subunits. No ragged-red fibers were present, and the only abnormal finding on light microscopy was universal small fibers in three of them. At the ultrastructural level, evidence of mitochondrial degeneration was observed in the form of lipofuscin formation in a case with NDUFS2 mutation and in the form of concentric laminated bodies in a case with NDUFS8 mutation.

Among the mitochondrial disorders, complex I deficiency is encountered frequently. The first mutation in the nuclear-encoded complex I gene was found in the NDUFS8 in a patient with Leigh-like presentation [3]. Subsequently, systematic sequencing analysis resulted in the identification of mutations in NDUFS1, NDUFS2, NDUFS4, NDUFS7, NDUFV1, and NDUFV2 genes, suggestive of a high prevalence of mutations in genes encoding for catalytic subunits in complex I [11].

Fresh quadriceps muscle biopsies were performed in four...

Keywords

Duchenne Muscular Dystrophy Mitochondrial Disorder Histological Hallmark Nuclear Mutation Thyrotoxic Periodic Paralysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Chretien D, Bourgeron T, Rotig A, Munnich A, Rustin P (1990) The measurement of the rotenone-sensitive NADH cytochrome c reductase activity in mitochondria isolated from minute amount of human skeletal muscle. Biochem Biophys Res Commun 173:26–33CrossRefPubMedGoogle Scholar
  2. 2.
    Goethem GV, Dermaut B, Lofgren A, Martin J, Van Broeckhoven C (2001) Mutation of POLG is associated with progressive external opthalmoplegia characterized by mtDNA deletions. Nat Genet 28:211–212CrossRefPubMedGoogle Scholar
  3. 3.
    Loeffen J, Smeitink J, Triepels R, Smeets R, Schuelke M, Sengers R, Trijbels F, Hamel B, Mullaart R, Heuvel L van den (1998) The first nuclear-encoded complex I mutation in a patient with Leigh syndrome. Am J Hum Genet 63:1598–1608Google Scholar
  4. 4.
    Loeffen JL, Elpeleg O, Smeitink J, Smeets R, Stockler-Ipsiroglu S, Mandel H, Sengers RC, Trijbels FJ, Heuvel L van den (2001) Mutations in the complex I NDUFS2 gene of patients with cardiomyopathy and encephalopathy. Ann Neurol 49:195–201CrossRefPubMedGoogle Scholar
  5. 5.
    Luft R, Ikkos D, Palmieri G, Ernster L, Afzelius B (1962) A case of severe hypermetabolism of nonthyroid origin with a defect in the maintenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J Clin Invest 41:1776–1804PubMedGoogle Scholar
  6. 6.
    Nishino I, Spinazzola A, Papadimitriou A, Hammans S, Steiner I, Hahn CD, Connolly AM, Verloes A, Guimaraes J, Maillard I, et al (2000) Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann Neurol 47:792–800CrossRefPubMedGoogle Scholar
  7. 7.
    Payne C, Curless R (1976) Concentric laminated bodies. J Neurol Sci 29:311–322CrossRefPubMedGoogle Scholar
  8. 8.
    Robinson BH (1998) Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect. Biochim Biophys Acta 1364:271–286PubMedGoogle Scholar
  9. 9.
    Schuelke M, Smeitink J, Mariman E, Loeffen JL, Plecko B, Trijbels FJ, Stockler-Ipsiroglu S, Heuvel L van den (1999) Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystriphy and myoclonic epilepsy. Nat Genet 21:260–261CrossRefPubMedGoogle Scholar
  10. 10.
    Sue CM, Karadimas C, Checcarelli N, Tanji K, Papadopoulou LC, Pallotti F, Guo FL, Shanske S, Hirano M, De Vivo DC, et al (2000) Differential features of patients with mutations in two COX assembly genes, SURF-1 and SCO2. Ann Neurol 47:589–595CrossRefPubMedGoogle Scholar
  11. 11.
    Ugalde C, Janssen RJ, Heuvel LP van den, Smeitink JA, Nijtmans LG (2004) Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency. Hum Mol Genet 13:659–667CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Argirios Dinopoulos
    • 1
    Email author
  • Jan Smeitink
    • 2
  • Henk ter Laak
    • 3
  1. 1.Cincinnati Children’s Hospital Medical CenterDivision of NeurologyCincinnatiUSA
  2. 2.Nijmegen Center for Mitochondrial DisordersRadboud University Nijmegen Medical CenterNijmegenThe Netherlands
  3. 3.Departments of Pathology and NeurologyRadboud University Nijmegen Medical CenterNijmegenThe Netherlands

Personalised recommendations