Elsevier

Neuromuscular Disorders

Volume 13, Issue 9, November 2003, Pages 757-764
Neuromuscular Disorders

Workshop report
116th ENMC international workshop: the treatment of mitochondrial disorders, 14th–16th March 2003, Naarden, The Netherlands

https://doi.org/10.1016/S0960-8966(03)00097-XGet rights and content

Introduction

Twenty participants from Denmark, Finland, France, Germany, Italy, Norway, Sweden, The Netherlands, the UK, and the USA met to discuss the treatment of mitochondrial disorders in children and adults. The group included adult and paediatric neurologists, metabolic paediatricians, an ophthalmologist, an endocrinologist, and other clinical scientists. The aim of the workshop was to define the extent of the clinical problem (the epidemiology of mitochondrial disease), discuss methods of assessing disease severity that might be used to assess treatment response, discuss the current best practice for the treatment of mitochondrial disease, and explore novel treatment strategies. During the workshop, the participants discussed their own clinical experience of the management of mitochondrial disease and by the end of the workshop, the participants produced two documents which are included in this report:

  • (i) A consensus statement on the current best practice for the treatment of mitochondrial disorders. This statement is a summary of the views of the participants. It is hoped that this statement will provide a benchmark for the current treatment of mitochondrial disease.

  • (ii) A draft clinical rating scale for mitochondrial disorders. There was universal agreement that a clinical rating scale should be weighted towards the impact of mitochondrial disease on the activities of daily living and quality of life. It is hoped that this scale will be refined and used for natural history studies and treatment trials in the future.

The participants recognised clear differences in the clinical management of young children with encephalomyopathies or multi-organ failure and older children who often have a more chronic disease course similar to adult patients. Different strategies are needed to monitor disease severity and clinically manage these two groups. These differences are reflected in the different sections of this report.

Section snippets

Defining the extent of the problem: the epidemiology of mitochondrial disease

Although mitochondrial disorders are still relatively rare, as a group, they are much more common than previously thought. There have been population-based studies of mitochondrial disorders in children and adults. The incidence of mitochondrial encephalomyopathies in preschool children (<6 years of age) was 1/11,000 and the point prevalence of mitochondrial encephalomyopathies in children under 16 was 1/21,000 in western Sweden [1]. Similar figures were found in a different population in

Measuring disease severity

Mitochondrial disorders can affect many different organ systems and the pattern of clinical involvement varies greatly from individual to individual. This poses a particular challenge when trying to measure disease severity in such a heterogeneous group of patients. The participants discussed the advantages and disadvantages of conventional and novel techniques for measuring the severity of mitochondrial disease.

Current best practice for the treatment of mitochondrial disorders

Much of our experience of the treatment of mitochondrial disease is based upon anecdotal reports and small case series. These reports must be interpreted with great caution. We do not have a clear picture of the natural history of mitochondrial disorders and many of the reported clinical improvements may just reflect a fluctuating disease course rather than a real effect of treatment. The participants also recognised the importance of prospective longitudinal natural history studies which will

Novel treatment approaches

Various novel treatment strategies were discussed. Aerobic training has been shown to be of benefit in patients with mitochondrial myopathy [19], but there are concerns that the percentage level of mutant mtDNA may increase in skeletal muscle in some patients [12] and the long-term consequences of this treatment are not known. The participants currently recommend that patients maintain an average level of activity, making sure that they do not become de-conditioned or exercise vigorously. A

Developing the European network and future proposals

The participants stressed the importance of the European collaboration to improve treatment for mitochondrial disease. It was agreed that the group should form an ENMC consortium and aim to meet again in 12–18 months to consolidate the links and compare prospectively collected natural history data and treatment experiences. Immediate aims would be to support a Cochrane review of the treatment of mitochondrial disease (ensuring that unpublished data is included) and develop an anonymous register

Acknowledgements

The workshop was made possible thanks to the financial support of the European Neuromuscular Centre (ENMC) and the main ENMC sponsors: Association Française contre les Myopathies (France), Deutsche Gesellschaft für Muskelkranke (Germany), Telethon Foundation (Italy); Muscular Dystrophy Campaign (UK), Musckelsvindfonden (Denmark), Prinses Beatrix Fonds (The Netherlands), Schwiezerische Stifung für die Erforschung der Muskelkrankheiten (Switzerland), Osterreichische Muskelforschung (Austria),

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