Skip to main content
PMC home page
Archives of Disease in Childhood logoLink to Archives of Disease in Childhood
. 1999 Sep;81(3):209–214. doi: 10.1136/adc.81.3.209

Multiple presentation of mitochondrial disorders

A Nissenkorn 1, A Zeharia 1, D Lev 1, A Fatal-Valevski 1, V Barash 1, A Gutman 1, S Harel 1, T Lerman-Sagie 1
PMCID: PMC1718054  PMID: 10451392

Abstract

The aim of this study was to assess the heterogeneous clinical presentations of children with mitochondrial disorders evaluated at a metabolic neurogenetic clinic. The charts of 36 children with highly suspected mitochondrial disorders were reviewed. Thirty one children were diagnosed as having a mitochondrial disorder, based on a suggestive clinical presentation and at least one of the accepted laboratory criteria; however, in five children with no laboratory criteria the diagnosis remained probable. All of the patients had nervous system involvement. Twenty seven patients also had dysfunction of other systems: sensory organs in 15 patients, cardiovascular system in five, gastrointestinal system in 20,urinary system in four, haematopoietic system in four, and endocrine system in nine. The clinical presentation was compatible with an established syndrome in only 15 children. Severe lactic acidosis or ragged red muscle fibres were encountered in very few patients. These results suggest that mitochondrial disorders should be evaluated in children presenting with a complex neurological picture or multisystem involvement.


Full Text

The Full Text of this article is available as a PDF (98.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barth P. G., Van den Bogert C., Bolhuis P. A., Scholte H. R., van Gennip A. H., Schutgens R. B., Ketel A. G. X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): respiratory-chain abnormalities in cultured fibroblasts. J Inherit Metab Dis. 1996;19(2):157–160. doi: 10.1007/BF01799418. [DOI] [PubMed] [Google Scholar]
  2. Birch-Machin M. A., Shepherd I. M., Watmough N. J., Sherratt H. S., Bartlett K., Darley-Usmar V. M., Milligan D. W., Welch R. J., Aynsley-Green A., Turnbull D. M. Fatal lactic acidosis in infancy with a defect of complex III of the respiratory chain. Pediatr Res. 1989 May;25(5):553–559. doi: 10.1203/00006450-198905000-00025. [DOI] [PubMed] [Google Scholar]
  3. Clarke L. A. Mitochondrial disorders in pediatrics. Clinical, biochemical, and genetic implications. Pediatr Clin North Am. 1992 Apr;39(2):319–334. doi: 10.1016/s0031-3955(16)38297-9. [DOI] [PubMed] [Google Scholar]
  4. Costeff H., Gadoth N., Apter N., Prialnic M., Savir H. A familial syndrome of infantile optic atrophy, movement disorder, and spastic paraplegia. Neurology. 1989 Apr;39(4):595–597. doi: 10.1212/wnl.39.4.595. [DOI] [PubMed] [Google Scholar]
  5. Crimmins D., Morris J. G., Walker G. L., Sue C. M., Byrne E., Stevens S., Jean-Francis B., Yiannikas C., Pamphlett R. Mitochondrial encephalomyopathy: variable clinical expression within a single kindred. J Neurol Neurosurg Psychiatry. 1993 Aug;56(8):900–905. doi: 10.1136/jnnp.56.8.900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DiMauro S., De Vivo D. C. Genetic heterogeneity in Leigh syndrome. Ann Neurol. 1996 Jul;40(1):5–7. doi: 10.1002/ana.410400104. [DOI] [PubMed] [Google Scholar]
  7. DiMauro S., Moraes C. T. Mitochondrial encephalomyopathies. Arch Neurol. 1993 Nov;50(11):1197–1208. doi: 10.1001/archneur.1993.00540110075008. [DOI] [PubMed] [Google Scholar]
  8. Elpeleg O. N., Ruitenbeek W., Jakobs C., Barash V., De Vivo D. C., Amir N. Congenital lacticacidemia caused by lipoamide dehydrogenase deficiency with favorable outcome. J Pediatr. 1995 Jan;126(1):72–74. doi: 10.1016/s0022-3476(95)70506-6. [DOI] [PubMed] [Google Scholar]
  9. Fischel-Ghodsian N., Prezant T. R., Fournier P., Stewart I. A., Maw M. Mitochondrial mutation associated with nonsyndromic deafness. Am J Otolaryngol. 1995 Nov-Dec;16(6):403–408. doi: 10.1016/0196-0709(95)90078-0. [DOI] [PubMed] [Google Scholar]
  10. Goto Y., Nonaka I., Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990 Dec 13;348(6302):651–653. doi: 10.1038/348651a0. [DOI] [PubMed] [Google Scholar]
  11. Holt I. J., Harding A. E., Petty R. K., Morgan-Hughes J. A. A new mitochondrial disease associated with mitochondrial DNA heteroplasmy. Am J Hum Genet. 1990 Mar;46(3):428–433. [PMC free article] [PubMed] [Google Scholar]
  12. Inbal A., Avissar N., Shaklai M., Kuritzky A., Schejter A., Ben-David E., Shanske S., Garty B. Z. Myopathy, lactic acidosis, and sideroblastic anemia: a new syndrome. Am J Med Genet. 1995 Jan 30;55(3):372–378. doi: 10.1002/ajmg.1320550325. [DOI] [PubMed] [Google Scholar]
  13. Jackson M. J., Schaefer J. A., Johnson M. A., Morris A. A., Turnbull D. M., Bindoff L. A. Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients. Brain. 1995 Apr;118(Pt 2):339–357. doi: 10.1093/brain/118.2.339. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Moraes C. T., Shanske S., Tritschler H. J., Aprille J. R., Andreetta F., Bonilla E., Schon E. A., DiMauro S. mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases. Am J Hum Genet. 1991 Mar;48(3):492–501. [PMC free article] [PubMed] [Google Scholar]
  16. Munnich A., Rötig A., Chretien D., Cormier V., Bourgeron T., Bonnefont J. P., Saudubray J. M., Rustin P. Clinical presentation of mitochondrial disorders in childhood. J Inherit Metab Dis. 1996;19(4):521–527. doi: 10.1007/BF01799112. [DOI] [PubMed] [Google Scholar]
  17. Munnich A., Rötig A., Chretien D., Saudubray J. M., Cormier V., Rustin P. Clinical presentations and laboratory investigations in respiratory chain deficiency. Eur J Pediatr. 1996 Apr;155(4):262–274. doi: 10.1007/BF02002711. [DOI] [PubMed] [Google Scholar]
  18. Riordan-Eva P., Harding A. E. Leber's hereditary optic neuropathy: the clinical relevance of different mitochondrial DNA mutations. J Med Genet. 1995 Feb;32(2):81–87. doi: 10.1136/jmg.32.2.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rustin P., Chretien D., Bourgeron T., Gérard B., Rötig A., Saudubray J. M., Munnich A. Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta. 1994 Jul;228(1):35–51. doi: 10.1016/0009-8981(94)90055-8. [DOI] [PubMed] [Google Scholar]
  20. Santorelli F. M., Shanske S., Macaya A., DeVivo D. C., DiMauro S. The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's syndrome. Ann Neurol. 1993 Dec;34(6):827–834. doi: 10.1002/ana.410340612. [DOI] [PubMed] [Google Scholar]
  21. Seibel P., Flierl A., Kottlors M., Reichmann H. A rapid and sensitive PCR screening method for point mutations associated with mitochondrial encephalomyopathies. Biochem Biophys Res Commun. 1994 Apr 29;200(2):938–942. doi: 10.1006/bbrc.1994.1540. [DOI] [PubMed] [Google Scholar]
  22. Servidei S., Zeviani M., Manfredi G., Ricci E., Silvestri G., Bertini E., Gellera C., Di Mauro S., Di Donato S., Tonali P. Dominantly inherited mitochondrial myopathy with multiple deletions of mitochondrial DNA: clinical, morphologic, and biochemical studies. Neurology. 1991 Jul;41(7):1053–1059. doi: 10.1212/wnl.41.7.1053. [DOI] [PubMed] [Google Scholar]
  23. Sherratt H. S., Watmough N. J., Johnson M. A., Turnbull D. M. Methods for study of normal and abnormal skeletal muscle mitochondria. Methods Biochem Anal. 1988;33:243–335. doi: 10.1002/9780470110546.ch6. [DOI] [PubMed] [Google Scholar]
  24. Sheu K. F., Hu C. W., Utter M. F. Pyruvate dehydrogenase complex activity in normal and deficient fibroblasts. J Clin Invest. 1981 May;67(5):1463–1471. doi: 10.1172/JCI110176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shoffner J. M., 4th, Wallace D. C. Oxidative phosphorylation diseases. Disorders of two genomes. Adv Hum Genet. 1990;19:267–330. [PubMed] [Google Scholar]
  26. Shoffner J. M., Lott M. T., Lezza A. M., Seibel P., Ballinger S. W., Wallace D. C. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell. 1990 Jun 15;61(6):931–937. doi: 10.1016/0092-8674(90)90059-n. [DOI] [PubMed] [Google Scholar]
  27. Shoffner J. M., Lott M. T., Voljavec A. S., Soueidan S. A., Costigan D. A., Wallace D. C. Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7952–7956. doi: 10.1073/pnas.86.20.7952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tulinius M. H., Holme E., Kristiansson B., Larsson N. G., Oldfors A. Mitochondrial encephalomyopathies in childhood. I. Biochemical and morphologic investigations. J Pediatr. 1991 Aug;119(2):242–250. doi: 10.1016/s0022-3476(05)80734-6. [DOI] [PubMed] [Google Scholar]
  29. Tulinius M. H., Holme E., Kristiansson B., Larsson N. G., Oldfors A. Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. J Pediatr. 1991 Aug;119(2):251–259. doi: 10.1016/s0022-3476(05)80735-8. [DOI] [PubMed] [Google Scholar]
  30. Wallace D. C. Mitochondrial genes and disease. Hosp Pract (Off Ed) 1986 Oct 15;21(10):77-87, 90-2. [PubMed] [Google Scholar]
  31. Zeharia A., Elpeleg O. N., Mukamel M., Weitz R., Ariel R., Mimouni M. 3-Methylglutaconic aciduria: a new variant. Pediatrics. 1992 Jun;89(6 Pt 1):1080–1082. [PubMed] [Google Scholar]
  32. Zeviani M., Bertagnolio B., Uziel G. Neurological presentations of mitochondrial diseases. J Inherit Metab Dis. 1996;19(4):504–520. doi: 10.1007/BF01799111. [DOI] [PubMed] [Google Scholar]
  33. Zeviani M., Gellera C., Antozzi C., Rimoldi M., Morandi L., Villani F., Tiranti V., DiDonato S. Maternally inherited myopathy and cardiomyopathy: association with mutation in mitochondrial DNA tRNA(Leu)(UUR). Lancet. 1991 Jul 20;338(8760):143–147. doi: 10.1016/0140-6736(91)90136-d. [DOI] [PubMed] [Google Scholar]
  34. Zeviani M., Servidei S., Gellera C., Bertini E., DiMauro S., DiDonato S. An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature. 1989 May 25;339(6222):309–311. doi: 10.1038/339309a0. [DOI] [PubMed] [Google Scholar]
  35. Zeviani M., Tiranti V., Piantadosi C. Mitochondrial disorders. Medicine (Baltimore) 1998 Jan;77(1):59–72. doi: 10.1097/00005792-199801000-00006. [DOI] [PubMed] [Google Scholar]

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group

RESOURCES