EP.03Mevalonate kinase deficiency - a mimic of mitochondrial myopathy in clinic and muscle biopsy

In 2011 a 43-year-old man with retinitis pigmentosa, cerebellar ataxia, mild mental retardation and myopathy was seen in our outpatient clinic. He showed a limb girdle patter of weakness and CK persistently> 1.000 U/l. Due to the suggestive combination of symptoms and a likewise affected brother, he was considered to have a mitochondrial disorder. This was supported by some COX-negative fibres in a myopathic vastus lateralis biopsy, but genetic analysis failed to confirm this. He returned to our clinic in 2019 reporting that his retinal disease had been attributed to compound heterocygeous mutations in the MVK gene by his treating ophthalmologist.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research

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Conclusion The key problem with the ND field is the lack of understanding in the events preceding the development of protein-based markers – such as Tau – currently used to diagnose NDs. By this stage, the diseases become more difficult to treat. SncRNAs play an important regulatory role in the maintenance of the homeostatic brain. Therefore, changes in their concentration levels can be indicative of mechanistic changes that could precede protein-based markers. One single sncRNA biomarker is unlikely to differentiate between diseases. However, a combination of sncRNA biomarkers could be illustrative of the me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Publication date: Available online 7 November 2018Source: Biochimica et Biophysica Acta (BBA) - BioenergeticsAuthor(s): Roza Kucharczyk, Alain Dautant, François Godard, Déborah Tribouillard-Tanvier, Jean-Paul di RagoAbstractProtons are transported from the mitochondrial matrix to the intermembrane space of mitochondria during the transfer of electrons to oxygen and shuttled back to the matrix by the a subunit and a ring of identical c subunits across the membrane domain (FO) of ATP synthase, which is coupled to ATP synthesis. A mutation (m.9176 T > G) of the mitochondrial ATP6 gene that replaces an u...
Source: Biochimica et Biophysica Acta (BBA) Bioenergetics - Category: Biochemistry Source Type: research
We report a case of a patient who had the mitochondrial cytopathy complex of neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome diagnosed at age 11 years with a biopsy-proven kidney involvement that progressed to end-stage renal disease at age 21 years. Mutations of mitochondrial DNA (mtDNA) are maternally inherited and lead to mitochondrial cytopathies with predominant neurologic manifestations: psychomotor retardation, epilepsy, ataxia, neuropathy, and myopathy. Given the ubiquitous nature of mitochondria, cellular dysfunction can also appear in tissues with high metabolic turnover; thus, there can be cardiac, ...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
Mitochondrial diseases are frequently associated with mutations in mitochondrial DNA (mtDNA). In most cases, mutant and wild-type mtDNAs coexist, resulting in heteroplasmy. The selective elimination of mutant mtDNA, and consequent enrichment of wild-type mtDNA, can rescue pathological phenotypes in heteroplasmic cells. Use of the mitochondrially targeted zinc finger-nuclease (mtZFN) results in degradation of mutant mtDNA through site-specific DNA cleavage. Here, we describe a substantial enhancement of our previous mtZFN-based approaches to targeting mtDNA, allowing near-complete directional shifts of mtDNA heteroplasmy, e...
Source: Nucleic Acids Research - Category: Research Authors: Tags: Molecular Biology Source Type: research
AbstractDefects in the respiratory chain or mitochondrial ATP synthase (complex V) result in mitochondrial dysfunction that is an important cause of inherited neurological disease. Two of the subunits of complex V are encoded byMT-ATP6 andMT-ATP8 in the mitochondrial genome. Pathogenic mutations inMT-ATP6 are associated with the Leigh syndrome, the syndrome of neuropathy, ataxia, and retinitis pigmentosa (NARP), as well as with non-classical phenotypes, whileMT-ATP8 is less frequently mutated in patients with mitochondrial disease. We investigated two adult siblings presenting with features of cerebellar ataxia, peripheral...
Source: Journal of Neurology - Category: Neurology Source Type: research
Conclusions: Only a minority of patients with MTATP6 mutations present with the classical LS and NARP syndromes. The vast majority of patients have an ataxia, peripheral neuropathy, and cognitive dysfunction and these should be considered core features in patients with genetic defects in MTATP6.Disclosure: Dr. Martikainen has nothing to disclose. Dr. Ng has nothing to disclose. Dr. Gorman has nothing to disclose. Dr. Schaefer has nothing to disclose. Dr. Horvath has nothing to disclose. Professor Patrick F. Chinnery has received research support from Santhera Pharmaceuticals. Dr. Blakely has nothing to disclose. Dr. Alston...
Source: Neurology - Category: Neurology Authors: Tags: Movement Disorders: Ataxias and Other Hyperkinetic Movement Disorders Source Type: research
A 21-year-old man presented with a 4-year history of seizures, visual hallucinations, cognitive decline, and gait impairment. Neurologic examination revealed myoclonic jerks, ataxia, and retinitis pigmentosa. Axillary skin biopsy showed Lafora bodies (figure). Lafora disease, the most common progressive myoclonic epilepsy with adolescent onset, is characterized by cognitive decline, visual hallucinations, myoclonus, generalized seizures, and pathognomonic inclusion bodies of polyglucosan found in cells of the skeletal muscle, skin, and brain.1,2 Retinitis pigmentosa is a hereditary pigmentary retinopathy commonly present i...
Source: Neurology - Category: Neurology Authors: Tags: Metabolic disease (inherited), Myoclonus; see Movement Disorders/myoclonus, All Epilepsy/Seizures NEUROIMAGES Source Type: research
Mitochondria are the power plants of the cell, a host of organelles evolved from symbiotic bacteria. They each carry a small amount of DNA, and this accumulates damage with age. Some sorts of damage can spread rapidly within a cell's mitochondria, causing all of them to become dysfunctional. The cell itself also malfunctions as a result, exporting damaging reactive molecules into surrounding tissues. A small but significant portion of all the cells in the body suffer this fate by the time old age rolls around, and their presence contributes to degenerative aging. Any comprehensive rejuvenation toolkit developed in the nea...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
ConclusionThis early research has developed a new technique to reduce the amount of mutation-carrying DNA within mitochondria. The hope is that this technique might be used in the eggs of women carrying disease-causing mitochondrial mutations.The government has recently given the go ahead for a technique that allows a woman who carries such a disease from passing it on to her child – making the UK the first country to do so. This technique has raised some ethical and safety concerns, as it places the woman’s chromosomes into a donor egg with healthy mitochondria. This means that once this egg is fertilised...
Source: NHS News Feed - Category: Consumer Health News Tags: Genetics/stem cells Pregnancy/child Source Type: news
Abstract Mitochondrial dysfunction and reactive oxygen species (ROS) induced oxidative damage are implicated in the pathogenesis of several human diseases. Based on our previous findings that ROS level was higher in human osteosarcoma cybrids - Neuropathy, Ataxia and Retinitis Pigmentosa (NARP) and was reduced by selenite treatment, this study was designed to elucidate the effects of selenite administration on oxidative and nitrosative damage to lipids, proteins and DNA. Oxidative and nitrosative damage to lipids and proteins was not increased in NARP cybrids or mitochondrial DNA-lacking Rho0 cells (displaying mit...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
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