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J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2012-303528
  • Neurogenetics
  • Short report

The UK MRC Mitochondrial Disease Patient Cohort Study: clinical phenotypes associated with the m.3243A>G mutation—implications for diagnosis and management

  1. Robert McFarland1
  1. 1Wellcome Trust Centre for Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
  2. 2MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK
  3. 3Neurogenetics Unit, National Hospital for Neurology and Neurosurgery, London, UK
  1. Correspondence to Dr Robert McFarland, Wellcome Trust Centre for Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; robert.mcfarland{at}ncl.ac.uk
  • Received 24 June 2012
  • Revised 24 December 2012
  • Accepted 26 December 2012
  • Published Online First 25 January 2013

Abstract

Background Population-based studies suggest the m.3243A>G mutation in MTTL1 is the most common disease-causing mtDNA mutation, with a carrier rate of 1 in 400 people. The m.3243A>G mutation is associated with several clinical syndromes including mitochondrial encephalopathy lactic acidosis and stroke-like episodes (MELAS), maternally inherited deafness and diabetes (MIDD) and progressive external ophthalmoplegia (PEO). Many patients affected by this mutation exhibit a clinical phenotype that does not fall within accepted criteria for the currently recognised classical mitochondrial syndromes.

Methods We have defined the phenotypic spectrum associated with the m.3243A>G mtDNA mutation in 129 patients, from 83 unrelated families, recruited to the Mitochondrial Disease Patient Cohort Study UK.

Results 10% of patients exhibited a classical MELAS phenotype, 30% had MIDD, 6% MELAS/MIDD, 2% MELAS/chronic PEO (CPEO) and 5% MIDD/CPEO overlap syndromes. 6% had PEO and other features of mitochondrial disease not consistent with another recognised syndrome. Isolated sensorineural hearing loss occurred in 3%. 28% of patients demonstrated a panoply of clinical features, which were not consistent with any of the classical syndromes associated with the m.3243A>G mutation. 9% of individuals harbouring the mutation were clinically asymptomatic.

Conclusion Following this study we propose guidelines for screening and for the management of confirmed cases.

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