“Myo-cardiomyopathy” is commonly associated with the A8344G “MERRF” mutation

Michela Catteruccia, Donato Sauchelli, Giacomo Della Marca, Guido Primiano, Cristina Cuccagna, Daniela Bernardo, Milena Leo, Antonella Camporeale, Tommaso Sanna, Alessandro Cianfoni, Serenella Servidei

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Abstract

The objective of the study was to better characterize the clinical phenotype associated with the A8344G “MERRF” mutation of mitochondrial DNA. Fifteen mutated patients were extensively investigated. The frequency of main clinical features was: exercise intolerance and/or muscle weakness 67 %, respiratory involvement 67 %, lactic acidosis 67 %, cardiac abnormalities 53 %, peripheral neuropathy 47 %, myoclonus 40 %, epilepsy 40 %, ataxia 13 %. A restrictive respiratory insufficiency requiring ventilatory support was observed in about half of our patients. One patient developed a severe and rapidly progressive cardiomyopathy requiring cardioverter-defibrillator implantation. Five patients died of overwhelming, intractable lactic acidosis. Serial muscle MRIs identified a consistent pattern of muscle involvement and progression. Cardiac MRI showed non-ischemic late gadolinium enhancement in the left ventricle inferolateral part as early sign of myocardial involvement. Brain spectroscopy demonstrated increased peak of choline and reduction of N-acetylaspartate. Lactate was never detected in brain areas, while it could be documented in ventricles. We confirm that muscle involvement is the most frequent clinical feature associated with A8443G mutation. In contrast with previous reports, however, about half of our patients did not develop signs of CNS involvement even in later stages of the disease. The difference may be related to the infrequent investigation of A8344G mutation in ‘pure’ mitochondrial myo-cardiomyopathy, representing a bias and a possible cause of syndrome’s underestimation. Our study highlights the importance of lactic acidosis and respiratory muscle insufficiency as critical prognostic factors. Muscle and cardiac MRI and brain spectroscopy may be useful tools in diagnosis and follow-up of MERRF.

Original languageEnglish
Pages (from-to)701-710
Number of pages10
JournalJournal of Neurology
Volume262
Issue number3
DOIs
Publication statusPublished - 2015

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Keywords

  • Cardiomyopathy
  • MERRF syndrome
  • Mitochondrial encephalomyopathies
  • Respiratory insufficiency

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Catteruccia, M., Sauchelli, D., Della Marca, G., Primiano, G., Cuccagna, C., Bernardo, D., Leo, M., Camporeale, A., Sanna, T., Cianfoni, A., & Servidei, S. (2015). “Myo-cardiomyopathy” is commonly associated with the A8344G “MERRF” mutation. Journal of Neurology, 262(3), 701-710. https://doi.org/10.1007/s00415-014-7632-0