Journal of the Formosan Medical Association
Volume 106, Issue 7 , Pages 528-536, 2007

A Follow-up Study in a Taiwanese Family with Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like Episodes Syndrome

  • Jie-Yuan Li

      Affiliations

    • Division of Neurology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Rong-Hong Hsieh

      Affiliations

    • School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan
    • ,
  • Nan-Jing Peng

      Affiliations

    • Departments of Nuclear Medicine Kaohsiung Veterans General Hospital, Kaohsiung and National Yang-Ming University, Taipei, Taiwan
    • ,
  • Ping-Hong Lai

      Affiliations

    • Departments of Nuclear Medicine and Radiology, Kaohsiung Veterans General Hospital, Kaohsiung and National Yang-Ming University, Taipei, Taiwan
    • ,
  • Cheng-Feng Lee

      Affiliations

    • Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Yuk-Keung Lo

      Affiliations

    • Division of Neurology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan
    • ,
  • Yau-Huei Wei

      Affiliations

    • Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Professor Yau-Huei Wei, Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, 155 Li-Nong Street, Section 2, Shih-Pai, Taipei 112, Taiwan

Received 30 November 2006; received in revised form 28 December 2006; accepted 13 March 2007.

Article Outline

Background/Purpose

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome is often associated with A3243G point mutation of mitochondrial DNA (mtDNA). We previously described a MELAS family characterized by harboring an additional ∼260 bp tandem duplication in the D-loop and a novel C3093G point mutation in the 16S rRNA gene of mtDNA in the proband. We studied the clinical progression and fluctuation of mtDNA mutations in this Taiwanese MELAS family.

Methods

We followed up the clinical course in all members of this family (1 proband, her mother and 3 sons) for 12 years. Mutations of mtDNA in serial muscle biopsies of the proband and blood samples and hair follicles taken at different time points from the members of this family were analyzed.

Results

The proband developed repeated stroke-like episodes, chronic intestinal pseudo-obstruction, polyneuropathy, progressive renal failure and dilated cardiomyopathy with heart failure. During the follow-up period, the mother and one of the siblings of the proband developed stroke-like episodes at age 62 and 12, respectively. There was no significant difference in the proportions of mtDNA with A3243G mutation among five serial muscle biopsies of the proband. In one carrier (I-2), the proportion of A3243G mutated mtDNA in blood cells was slightly increased with disease progression.

Conclusion

This study underlines the importance of early detection of extraneuromuscular symptoms in the members of a family with MELAS syndrome by adequate follow-up. The age of onset of stroke-like episode in MELAS syndrome may be as late as 62 years. We suggest that the manifestations of MELAS syndrome in this family might be associated with the additional ∼260 bp tandem duplication in the D-loop region and the coexistence of C3093G mutation in the 16S rRNA gene with the A3243G mutation of mtDNA.

Key Words:  follow-up study , MELAS , mitochondrial disease , mitochondrial DNA , mutation

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PII: S0929-6646(07)60003-5

doi:10.1016/S0929-6646(07)60003-5

Journal of the Formosan Medical Association
Volume 106, Issue 7 , Pages 528-536, 2007

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