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Atypical presentation of multisystem disorders in two girls with mitochondrial DNA deletions

  • Metabolic Diseases
  • Original Paper
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Abstract

We describe two girls with atypical presentations of multisystem disorders due to deletions in mitochondrial DNA (mtDNA). One presented with painful carpopedal spasms due to hypoparathyroidism at the age of 4 years. The disease was rapidly progressive with development of truncal and limb ataxia, spastic paraparesis, muscle weakness and wasting, pigmentary retinal degeneration and sensorineural hearing loss. She had short stature and vitiligo patches, hirsutism, anaemia, diabetes mellitus and exocrine pancreatic dysfunction. The other girl presented at the age of 6 years with polydipsia, polyuria and fatigue due to renal tubular dysfunction. The disease was insidiously progressive with poor growth and development of sensorineural hearing loss, muscle weakness and truncal and limb ataxia. Morphological, enzyme histochemical and biochemical investigations indicated mitochondrial dysfunction of skeletal muscle, liver and kidney in one patient and of skeletal muscle and liver in the other. Both patients had large proportions of mtDNA molecules with deletion in liver, kidney, skeletal muscle and blood cells.

Conclusion

It may be concluded that symptoms from several different organs may be the first manifestation of a mtDNA deletion disorder.

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Abbreviations

COX :

cytochrome c oxidase

KSS :

Kearns-Sayre syndrome

mtDNA :

mitochondrial DNA

SDH :

Succinate dehydrogenase

References

  1. Bordarier C, Duyckaerts C, Robain O, Ponsot G, Laplane D (1990) Kearns-Sayre syndrome. Two clinico-pathological cases. Neuropediatrics 21:106–109

    PubMed  Google Scholar 

  2. Borulf S, Lindberg T (1982) Immunoactive trypsin in duodenal juice from children with gastrointestinal disorders. Gut 23:564–568

    PubMed  Google Scholar 

  3. Cormier V, Rötig A, Quartino AR, Forni GL, Cerone R, Maier M, Saudubray J-M, Munnich A (1990) Widespread multitissue deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome. J Pediatr 117:599–602

    PubMed  Google Scholar 

  4. Curless RG, Flynn J, Bachynski B, Gregorios JB, Benke P, Cullen R (1986) Fatal metabolic acidosis and coma after steroid therapy for KSS. Neurology 36: 872–873

    PubMed  Google Scholar 

  5. Eviatar L, Shanske S, Gauthier B, Abrams C, Maytal J, Slavin M, Valderrama E, DiMauro S (1990) Kearns-Sayre syndrome presenting as renal tubular acidosis. Neurology 40:1761–1763

    PubMed  Google Scholar 

  6. Goto Y-i, Itami N, Kajii N, Tochimaru H, Endo M, Horai S (1990) Renal tubular involvement mimicking Bartter syndrome in a patient with Kearns-Sayre syndrome. J Pediatr 116:904–910

    PubMed  Google Scholar 

  7. Harvey JN, Barnett D (1992) Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol 37:97–104

    Google Scholar 

  8. Holt IJ, Harding AE, Morgan-Hughes JA (1988) Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies. Nature 331: 717–719

    Article  PubMed  Google Scholar 

  9. Kadowaki T, Kadowaki H, Mori Y, Tohe K, Sakuta R, Suzuki Y, Tanabe Y, Sakura H, Awata T, Goto Y-i, Hayakawa T, Matsuoka K, Kawamori R, Kamada T, Horai S, Nonaka I, Haguka R, Akanuma Y, YazAki Y (1994) A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med 330:962–968

    Article  PubMed  Google Scholar 

  10. Larsson N-G, Holme E (1992) Multiple short direct repeats associated with single mtDNA deletions. Biochim Biophys Acta 1139:311–314

    PubMed  Google Scholar 

  11. Larsson N-G, Holme E, Kristiansson B, Oldfors A, Tulinius M (1990) Progressive increase of the mutated mitochondrial DNA fraction in Kearns-Sayre syndrome. Pediatr Res 28:131–136

    PubMed  Google Scholar 

  12. Lestienne P, Ponsot G (1988) Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet I:885

    Article  Google Scholar 

  13. Majander A, Suomalainen A, Vettenranta K, Sariola H, Perkkiö M, Holmberg C, Pihko H (1991) Congential hypoplastic anemia, diabetes, and severe renal tubular dysfunction associated with a mitochondrial DNA deletion. Pediatr Res 30:327–330

    PubMed  Google Scholar 

  14. Mita S, Schmidt B, Schon EA, DiMauro S, Bonilla E (1989) Detection of “deleted” mitochondrial genomes in cytochrome-c oxidase-deficient muscle fibers of patients with Kearns-Sayre syndrome. Proc Natl Acad Sci USA 86:9509–9513

    PubMed  Google Scholar 

  15. Moraes CT, DiMauro S, Zeviani M, Lombes A, Shanske S, Miranda AF, Nakase H, Bonilla E, Werneck LC, Servidei S, Nonaka I, Koga Y, Spiro AJ, Brownell KW, Schmidt B, Schotland DL, Zupanc M, De Vivo DC, Schon EA, Rowland LP (1989) Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 320:1293–1299

    PubMed  Google Scholar 

  16. Moraes CT, Zeviani M, Schon EA, Hickman RO, Vlcek BW, DiMauro S (1991) Mitochondrial DNA deletion in a girl with manifestations of Kearns-Sayre and Lowe syndromes: An example of phenotypic mimicry? Am J Med Gen 41:301–305

    Article  Google Scholar 

  17. Mori K, Narahara K, Ninomiya S, Goto Y-i, Nonaka I (1991) Renal and skin involvement in a patient with complete Kearns-Sayre syndrome. Am J Med Gen 38:583–587

    Article  Google Scholar 

  18. Oldfors A, Sommerland H, Holme E, Tulinius M, Kristiansson B (1989) Cytochrome c oxidase deficiency in infancy. Acta Neuropathol 77:267–275

    Article  PubMed  Google Scholar 

  19. Oldfors A, Larsson N-G, Holme E, Tulinius M, Kadenbach B, Droste M (1992) Mitochondrial DNA deletions and cytochrome c oxidase deficiency in muscle fibres. J Neurol Sci 110:169–177

    Article  PubMed  Google Scholar 

  20. Ponzetto C, Bresolin N, Bordoni A, Moggio M, Meola G, Bet L, Prelle A, Scarlato G (1990) Kearns-Sayre syndrome: different amounts of deleted mitochondrial DNA are present in several autoptic tissues. J Neurol Sci 96: 207–210

    Article  PubMed  Google Scholar 

  21. Rötig A, Colonna M, Blanche S, Fischer A, Le Deist F, Frezal J, Saudubray J-M, Munnich A (1988) Deletion of blood mitochondrial DNA in pancytopenia. Lancet II:567–568

    Article  Google Scholar 

  22. Rötig A, Colonna M, Bonnefont JP, Blanche S, Fischer A, Saudubray J-M, Munnich A (1989) Mitochondrial DNA deletion in Pearson's marrow/pancreas syndrome. Lancet I: 902–903

    Article  Google Scholar 

  23. Rötig A, Cormier V, Blanche S, Bonnefont J-P, Ledeist F, Romero N, Schmitz J, Rustin P, Fischer A, Saudubray J-M, Munnich A (1990) Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest 86:1601–1608

    PubMed  Google Scholar 

  24. Rötig A, Cormier V, Chatelain P, Francois R, Saudubray J-M, Rustin R, Munnich A (1992) Deletion of mitochondrial DNA in a case of early-onset diabetes mellitus, optic atrophy and deafness (Wolfram syndrome, MIM 222300). J Clin Invest 91:1095–1098

    Google Scholar 

  25. Sano T, Ban K, Ichiki T, Kobayashi M, Tanaka M, Ohno K, Ozawa T (1993) Molecular and genetic analyses of two patients with Pearson's marrow-pancreas syndrome. Pediatr Res 34:105–110

    PubMed  Google Scholar 

  26. Shanske S, Moraes CT, Lombes A, Miranda AF, Bonilla E, Lewis P, Whelan MA, Ellsworth CA, DiMauro S (1990) Widespread tissue distribution of mitochondrial DNA deletions in Kearns-Sayre syndrome. Neurology 40: 24–28

    PubMed  Google Scholar 

  27. Superti-Furga A, Schoenle E, Tuchschmid P, Caduff R, Sabato V, Demattia D, Gitzelmann R, Steinmann B (1993) Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal hemoglobin caused by deletion and duplication of mitochondrial DNA. Eur J Pediatr 152:44–50

    PubMed  Google Scholar 

  28. Tulinius MH, Holme E, Kristiansson B, Larsson N-G, Oldfors A (1991) Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations. J Pediatr 119: 242–250

    PubMed  Google Scholar 

  29. Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon E, Rowland LP (1988) Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 38:1339–1346

    PubMed  Google Scholar 

  30. Zeviani M, Bresolin N, Gellera C, Bordoni A, Pannacci M, Amati P, Moggio M, Servidei S, Scarlato G, DiDonato S (1990) Nucleus-driven mutiple largescale deletions of the human mitochondrial genome: A new autosomal dominant disease. Am J Hum Genet 47: 904–914

    PubMed  Google Scholar 

  31. Zupanc ML, Moraes CT, Shanske S, Langman CB, Ciafaloni E, DiMauro S (1991) Detetion of mitochondrial DNA in patients with combined features of Kearns-Sayre and MELAS syndromes. Ann Neurol 29:680–683

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatrics, University of Göteborg Östra Hospital, S-416 85, Göteborg, Sweden

    Már H. Tulinius, Nils-Göran Larsson, Lars Sigström & Bengt Kristiansson

  2. Department of Pathology, University of Göteborg, Sahlgrenska Hospital, S-41345, Göteborg, Sweden

    Anders Oldfors

  3. Department of Clinical Chemistry, University of Göteborg, Sahlgrenska Hospital, S-41345, Göteborg, Sweden

    Elisabeth Holme, Nils-Göran Larsson & Massoud Houshmand

  4. Department of Paediatrics, Boden Hospital, S-96185, Boden, Sweden

    Per Fahleson

Authors
  1. Már H. Tulinius
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  2. Anders Oldfors
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  3. Elisabeth Holme
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  4. Nils-Göran Larsson
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  5. Massoud Houshmand
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  6. Per Fahleson
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  7. Lars Sigström
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  8. Bengt Kristiansson
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Tulinius, M.H., Oldfors, A., Holme, E. et al. Atypical presentation of multisystem disorders in two girls with mitochondrial DNA deletions. Eur J Pediatr 154, 35–42 (1995). https://doi.org/10.1007/BF01972970

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  • DOI: https://doi.org/10.1007/BF01972970

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