When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis?

Abstract

Myoclonic epilepsy associated with ragged red fibers (MERRF) is a rare mitochondrial disorder. Diagnostic criteria for MERRF include typical manifestations of the disease: myoclonus, generalized epilepsy, cerebellar ataxia and ragged red fibers (RRF) on muscle biopsy. Clinical features of MERRF are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNA Lys gene of the DNAmt, mainly A8344G, are responsible for almost 90% of MERRF cases. Morphological changes seen upon muscle biopsy in MERRF include a substantive proportion of RRF, muscle fibers showing a deficient activity of cytochrome c oxidase (COX) and the presence of vessels with a strong reaction for succinate dehydrogenase and COX deficiency. In this review, we discuss mainly clinical and laboratory manifestations, brain images, electrophysiological patterns, histology and molecular findings as well as some differential diagnoses and treatments.Keywords: MERRF, mitochondrial, epilepsy, myoclonus, myopathy. RESUMOEpilepsia mioclônica associada com fibras vermelhas rasgadas (MERRF) é uma rara doença mitocondrial. O critério diagnóstico para MERRF inclui as manifestações típicas da doença: mioclonia, epilepsia generalizada, ataxia cerebelar e fibras vermelhas rasgadas (RRF) na biópsia de músculo. Na fase inicial da doença, as manifestações clínicas podem não ser uniformes, e correlação entre as manifestações clínicas e fisiopatologia não estão completamente elucidadas. Estima-se que as mutações de ponto no gene tRNA Lys do DNAmt, principalmente a A8344G, sejam responsáveis por quase 90% dos casos de MERRF. As alterações morfológicas na biópsia muscular incluem uma grande proporção de RRF, fibras musculares com deficiência de atividade da citocromo c oxidase (COX) e presença de vasos com forte reação para succinato desidrogenase e deficiência da COX. Nesta revisão, são discutidas as principais manifestações clínicas e laboratoriais, imagens cerebrais, padrões eletrofisiológicos, histológicos e alterações moleculares, bem como, alguns dos diagnósticos diferenciais e tratamentos.

Diagnosing MERRF requires clinical and genetic evidence

“…In addition, we considered it to be beyond the field of our study to include all clinical data of the patient, especially if the results of these tests were within the accepted norms, such as the level of lactate dehydrogenase. The estimated data indicate that the mutation 8344A> G in the MTTK gene is responsible for the occurrence of the MERRF syndrome in as many as 80% of the investigated cases [4]. In our case report, the reference of this mutation to the phenotype of the mitochondrial multiorgan disorder syndrome (MIMODS) instead of the phenotype of the MERRF syndrome raises our doubts.…”

Myoclonic epilepsy with ragged-red fibers (MERRF) – clinical and electrophysiological analysis

“…Gen tRNALys (inaczej Mt-tk, trNk) został zlokalizowany między nukleotydami 8295 a 8364 mtDNa. stwierdzono, że za większość przypadków MerrF (80-90%) jest odpowiedzialna punktowa mutacja nukleotydu 8344, w którym adenina została wymieniona na guaninę (a8344G) [1]. U chorych z MerrF opisano również inne mutacje, np.…”

“…MerrF charakteryzuje się dużą zmiennością fenotypową, zwłaszcza we wczesnym stadium choroby [1,12]. W postaci zaawansowanej manifestacja kliniczna MerrF staje się bardziej jednolita.…”

Pathology of skeletal muscle fibers and small blood vessels in MERRF syndrome: an ultrastructural study

“…Other multisystemic alterations can also be found, e.g. deafness, exercise intolerance, dementia, peripheral neuropathy, short stature, abnormal cardiac conduction, cardiomyopathies, ophthalmoparesis, pigmentary retinopathy, and lipoma [19,20,21].…”

“…Other mutations in mitochondrial genes, including but not limited to: m.8356 T>C, m.8361 G>A, and m.8363 G>A, account for another 10% and m.611 G>A and m.15967 G>A for the other 5%. The remaining mu-tations, for example m.611 G>A and m.15967 G>A, account for less than 5% of cases, but up to 10% of MERRF patients still have no identifiable mutations in mtDNA [19,21].…”