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

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.

Expanded phenotypic spectrum of the m.8344A>G “MERRF” mutation: data from the German mitoNET registry

“…Although depression, post-partum psychosis and anxiety disorders have previously been described in patients with the m.8344A[G mutation [21,22], other authors only rarely found psychiatric involvement in those patients (3 %) [19]. Migraine, representing another CNS symptom, was more frequently present in our cohort (52 %) compared to other studies, such as Mancuso et al [19] with only 9 % (Fig.…”

“…2). In another recent publication of 15 patients with the m.8344A[G mutation, 67 % showed restrictive respiratory insufficiency, of which 78 % needed nocturnal ventilatory support or tracheostomy [22]. Another previously reported patient with the m.8344A[G mutation presented distal and facial weakness as well as respiratory insufficiency ultimately leading to the necessity of noninvasive nocturnal ventilatory support [23].…”

Peripheral neuropathy is a common manifestation of mitochondrial diseases: a single‐centre experience

“…Neuropathy was found in 6.8% of patients in a large retrospective study [19] and in 47% of patients in our previous single-centre study on MERRF [20]. Neuropathy was found in 6.8% of patients in a large retrospective study [19] and in 47% of patients in our previous single-centre study on MERRF [20].…”

“…In patients harbouring the A8344G mutation polyneuropathy is frequently described in single case records, whilst very few studies have been reported on larger groups of patients. Neuropathy was found in 6.8% of patients in a large retrospective study [19] and in 47% of patients in our previous single-centre study on MERRF [20].…”

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

“…typowy obraz kliniczny obejmuje mioklonie, napady padaczkowe, ataksję móżdżkową, jak również miopatię z charakterystycznymi zmianami w bioptatach mięśni [8]. Do rzadziej obserwowanych objawów, także uszkodzenia innych organów, należą: głuchota, wolno postępujące otępienie, neuropatia, niski wzrost, nietolerancja wysiłku, zaburzenia przewodnictwa sercowego, kardiomiopatia, oftalmoplegia, zanik nerwu wzrokowego, zwyrodnienie barwnikowe siatkówki, liczne tłuszczaki na szyi i tułowiu [9][10][11]. Mioklonie w MerrF mogą pojawić się w sposób izolowany lub w łączności z uogólnionymi napadami drgawkowymi.…”