Abstract
Myoclonic epilepsy with ragged red fibres (MERRF) and mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) are established phenotypes of mitochondrial encephalopathies. Nearly all patients affected by MERRF harbour a mutation in the mitochondrial tRNALys gene. We report a 13-year-old patient who presented with the classical phenotype of MERRF but was found with the typical mutation of MELAS. The patient presented with myoclonic epilepsy beginning at 10 years of age, a muscle biopsy with ragged red fibres and some COX negative fibres and progressive bilateral MRI hyperintensitivities in the basal ganglia constituting MERRF syndrome but lacked clinical characteristics of MELAS. In particular, stroke-like episodes or lactic acidosis were not present. None of the tRNA mutations described in MERRF were found. However, further analyses showed the tRNALeu mutation m.3243A>G usually found in MELAS to be responsible for the condition in this patient. This report highlights the broad phenotypic variability of mitochondrial encephalopathies with juvenile onset. It shows that m.3243A>G mutations can cause classical MERRF and emphasises the significance of comprehensive genetic studies if mitochondrial disease is suspected clinically.
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References
Corona P, Lamantea E, Greco M, Carrara F, Agostino A, Guidetti D, Dotti MT, Mariotti C, Zeviani M (2002) Novel heteroplasmic mtDNA mutation in a family with heterogeneous clinical presentations. Ann Neurol 51(1):118–122
Fabrizi GM, Cardaioli E, Grieco GS, Cavallaro T, Malandrini A, Manneschi L, Dotti MT, Federico A, Guazzi G (1996) The A to G transition at nt 3243 of the mitochondrial tRNALeu(UUR) may cause an MERRF syndrome. J Neurol Neurosurg Psychiatry 61(1):47–51
Filosto M, Tomelleri G, Tonin P, Scarpelli M, Vattemi G, Rizzuto N, Padovani A, Simonati A (2007) Neuropathology of mitochondrial diseases. Biosci Rep 27(1–3):23–30
Folgero T, Torbergsen T, Oian P (1995) The 3243 MELAS mutation in a pedigree with MERRF. Eur Neurol 35(3):168–171
Hammans SR, Sweeney MG, Hanna MG, Brockington M, Morgan-Hughes JA, Harding AE (1995) The mitochondrial DNA transfer RNALeu(UUR) A–>G(3243) mutation. A clinical and genetic study. Brain 118(Pt 3):721–734
Ito S, Shirai W, Asahina M, Hattori T (2008) Clinical and brain MR imaging features focusing on the brain stem and cerebellum in patients with myoclonic epilepsy with ragged-red fibers due to mitochondrial A8344G mutation. AJNR Am J Neuroradiol 29(2):392–395
Nakamura M, Yabe I, Sudo A, Hosoki K, Yaguchi H, Saitoh S, Sasaki H (2010) MERRF/MELAS overlap syndrome: a double pathogenic mutation in mitochondrial tRNA genes. J Med Genet 47(10):659–664
Panetta J, Smith L, Boneh A (2004) Effect of high dose vitamins, coenzyme Q, and high fat diet in paediatric patients with mitochondrial diseases. J Inher Metab Dis 27:487–498
Santa KM (2010) Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Pharmacotherapy 30(11):1179–1196
Van Goethem G, Mercelis R, Lofgren A, Seneca S, Ceuterick C, Martin JJ, Van Broeckhoven C (2003) Patient homozygous for a recessive POLG mutation presents with features of MERRF. Neurology 61(12):1811–1813
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Brackmann, F., Abicht, A., Ahting, U. et al. Classical MERRF phenotype associated with mitochondrial tRNALeu (m.3243A>G) mutation. Eur J Pediatr 171, 859–862 (2012). https://doi.org/10.1007/s00431-011-1662-8
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DOI: https://doi.org/10.1007/s00431-011-1662-8