Prevalence and progression of mitochondrial diseases: a study of 50 patients.
ABSTRACT We report 50 patients with various clinical phenotypes of mitochondrial disease studied over the past 10 years in a large urban area (Madrid Health Area 5). The clinical phenotypes showed a large variety of abnormalities in molecular biology and biochemistry. The prevalence of mitochondrial diseases was found to be 5.7 per 100,000 in the population over 14 years of age. Clinical and electrophysiological assessment reveal signs of neuropathy in 10 patients. Electromyographic findings consistent with myopathy were obtained in 37 cases. Six patients died of medical complications. Disease phenotype influenced survival to some degree (P < 0.01). Age of onset and gender were not associated with differences in survival. Mitochondrial disease is thus far more common than expected and a common cause of chronic morbidity.
SourceAvailable from: Emilio José Laserna-MendietaLaboratorio y Enfermedad: Casos Clínicos Vol.2, 1st edited by Asociación Española de Biopatología Médica, 10/2010: chapter Caso 12: pages 88-94; , ISBN: 978-84-614-3808-2
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ABSTRACT: Mitochondria are organelles responsible for production of most energy through oxidative phosphorylation process (OXPHOS). It contains a double strand DNA (mitDNA) of about 16,500 bp encoding two ribosomal RNAs and 37 mitochondrial proteins. Mutation in mitDNA may result in multisystem syndromes known as mitochondrial diseases, affecting predominantly tissues that require high levels of ATP such as skeletal muscle (mitochondrial myopathies), brain (e.g. MELAS, MERRF, LHON e NARP), liver, kidney (Fanconi syndrome), heart and endocrine glands (Pearson syndrome). A case of mitochondrial disease was first reported in 1962 and correlation of such disease with mutations in mitDNA gained scientific importance in late 1980's. There are 150 alterations reported in mitDNA capable of producing metabolic dysfunctions of clinical relevance. To date, no standard protocol for diagnosis of mitochondrial diseases has been established, partially due to the wide amplitude of clinical manifestation generally observed. A combined analysis of clinical data, biochemical, morphological and laboratory tests must be performed to evaluate mitochondrial respiratory chain activity and integrity of nuclear and mitochondrial genomes. Currently, there are no effective treatments available for mitochondrial diseases, but only palliative therapeutics using conventional strategies to relieve symptoms. Thus, gene therapy emerges as potential therapeutic strategy for more efficient treatment of mitochondrial diseases.
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ABSTRACT: Mitochondrial DNA (mtDNA) analysis is centralized in the Department of Neuropathology, Beaumont Hospital. Services offered include analysis of common mtDNA point mutations, large scale mtDNA deletions/rearrangements, and sequencing of the nuclear gene POLG. The aims of this study were to audit the mtDNA diagnostic service over a 10-year period, to determine appropriate use of the service, and to improve efficient use of the service by devising a requisition form that includes diagnostic algorithms. Between July 2002 and October 2013, 716 samples were received for analysis. Overall, the number of confirmed mutations was low. Lack of diagnostic algorithms may result in expansive, unrefined requests, leading to costly investigations. We introduced a requisition form that extracts clinical, biochemical, and pathological data prior to analysis. With this information, diagnostic algorithms can be applied to select the most relevant mutations for initial analysis and also to increase the incidence of mutation detection.Clinical neuropathology 07/2014; 33(4):279-83. DOI:10.5414/NP300722 · 1.31 Impact Factor