Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A report is given of an association of dyssynergia cerebellaris myoclonica associated with Friedreich's ataxia and mitochondrial myopathy in 2 patients. They had suffered from gradually increasing bursts of myoclonus since the wage of 14 and childhood, respectively. The other striking clinical features included generalized convulsions, mental deterioration, intention tremor, ataxia, muscular atrophy and deformity of feet. Muscle biopsies revealed ragged-red fibres in both cases. On electron microscopy these fibres contained subsarcolemnal aggregations of abundant abnormal mitochondria with proliferation of inner membranes or paracrystalline inclusions. One of these patients showed elevated blood lactate and pyruvate with an increased lactate/pyruvate ration, apparently of primary origin. These 2 cases resemble those reported briefly by Tsairis et al. (1974). An association of dyssynergia cerebellaris myoclonica associated with Friedreich's ataxia and mitochondrial myopathy in these 2 patients is unlikely to be coincidental but may represent one nosological entity. This myoclonus epilepsy syndrome associated with ragged-red fibres is compared with other possibly related mitochondrial encephalomyopathies.
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PMID:Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities ): disease entity or a syndrome? Light-and electron-microscopic studies of two cases and review of literature. 677 61

Developments in the field of Huntington's disease have focused on the potential benefits of predictive testing. Markers have been described for autosomal dominant cerebellar ataxia and for certain subtypes of Friedrich's ataxia. Argentophilic neuronal and glial inclusions appear to be the first specific pathologic hallmark of multiple system atrophy. "Pure" hereditary spastic paraplegia is not a multisystem disorder of the central nervous system, but a monomorphic and stereotyped disease. Advances in Tourette's syndrome are limited because the presumed gene eludes identification. A new type of myoclonus, propiospinal myoclonus, has been described. Clinical and electrophysiologic criteria for defining primary orthostatic tremor have been proposed. Understanding of the neurophysiologic substrate of essential tremor and myoclonus is improving. New neurologic disorders presenting clinically with prominent movement disorder continue to be described.
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PMID:Choreas, hereditary and other ataxias, tics, myoclonus, and other movement disorders. 850 6

MERRF is an acronym of myoclonus epilepsy associated with ragged-red fibers and was first reported as a new nosological entity belonging to mitochondrial encephalomyopathies in San Remo symposium on "Mitochondrial Pathology" in 1982. MERRF was named Fukuhara disease by Rowland (1983). The first reported patient had been diagnosed as having Ramsay Hunt syndrome associated with Friedreich's ataxia. However, nowadays, the previously reported cases as having Ramsay Hunt syndrome associated with Friedreich's ataxia are regarded as having been suffered from MERRF. The history in establishing the nosological entity of MERRF was described. Patients with MERRF develop myoclonus, epileptic seizures, cerebellar ataxia, dementia, sensorineural hearing disturbance, optic atrophy, muscular wasting, and foot deformities at the advanced stage. Pathological findings show degeneration of the dentate nuclei, globus pallidus, and red nuclei, substantia nigra, inferior olivary nuclei, cerebellar cortex, and spinal cord. The posterior columns, the spinocerebellar tracts, and Clark's columns are degenerating in the spinal cord. The pyramidal tracts never show a severe degeneration as in Friedreich's ataxia. The skeletal muscles show mitochondrial abnormalities histologically and electron microscopically. Clinical features of MERRF are not necessarily uniform in the early stage and muscle biopsy findings are also very mild in some patients with MERRF, necessitating genetic analysis for diagnosis. Most of patients show a point mutation (A --> G) of nt 8344 in mitochondrial DNA.
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PMID:[Fukuhara disease]. 1823 33

The spinocerebellar ataxias (SCA) are a large group of inherited disorders affecting the cerebellum and its afferent and efferent pathways. Their hallmark symptom is slowly progressive, symmetrical, midline, and appendicular ataxia. Some may also have associated hyperkinetic movements (chorea, dystonia, myoclonus, postural/action tremor, restless legs, rubral tremor, tics), which may aid in differential diagnosis and provide treatable targets to improve performance and quality of life in these progressive, incurable conditions. The typical dominant ataxias with associated hyperkinetic movements are SCA1-3, 6-8, 12, 14, 15, 17, 19-21, and 27. The common recessive ataxias with associated hyperkinetic movements are ataxia telangiectasia and Friedreich's ataxia. Fragile X tremor-ataxia syndrome (FXTAS) and multiple-system atrophy (a sporadic ataxia which is felt to have a genetic substrate) also have hyperkinetic features. A careful work-up should be done in all apparently sporadic cases, to rule out acquired causes of ataxia, some of which can cause hyperkinetic movements in addition to ataxia. Some testing should be done even in individuals with a confirmed genetic cause, as the presence of a secondary factor (nutritional deficiency, thyroid dysfunction) can contribute to the phenotype.
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PMID:Spinocerebellar degenerations. 2149 73

Mutations in the mitochondrial DNA polymerase gamma (POLG) cause a highly pleomorphic disease spectrum, and reports about their frequencies in ataxia populations yield equivocal results. This leads to uncertainties about the role of POLG genetics in the workup of patients with unexplained ataxia. A comprehensive characterization of POLG-associated ataxia (POLG-A) will help guide genetic diagnostics and advance our understanding of the disease processes underlying POLG-A. Thirteen patients with POLG-A were assessed by standardized clinical investigation, nerve conduction studies, motor-evoked potentials, magnetic resonance imaging (MRI) and transcranial sonography (TCS). The findings were compared with 13 matched patients with Friedreich's ataxia (FA). In addition to the well-known POLG-associated features of chronic external ophthalmoplegia (100 %), areflexia to the lower extremity (100 %), impaired vibration sense (100 %), bilateral ptosis (69 %) and epilepsy (38 %), also hyperkinetic movement disorders were frequent in POLG-A patients, including chorea (31 %), dystonia (31 %) and myoclonus (23 %). Similar to FA, polyneuropathy was of sensory axonal type (100 %). In contrast to FA, none of the POLG-A patients showed impaired central motor conduction. TCS demonstrated less enlargement of the fourth ventricle and more diffuse cerebellar hyperechogenicity in POLG-A. Corresponding to TCS, MRI revealed no or only mild cerebellar atrophy in most POLG-A patients (85 %). POLG ataxia presents with the clinical characteristics of both afferent and cerebellar ataxia. Cerebellar alterations diffusely involve various parts of the cerebellum, yet cerebellar atrophy is generally mild. POLG-A presents with a high load of distinct non-ataxia features, namely, sensory neuropathy, external ophthalmoplegia, ptosis, epilepsy and/or hyperkinetic movement disorders. Involvement of the corticospinal tract, however, is rare.
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PMID:Characterizing POLG ataxia: clinics, electrophysiology and imaging. 2252 63

Mitochondrial diseases (MIDs) are a large group of heterogeneous disorders due to mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) genes, the latter encoding proteins involved in mitochondrial function. A multisystem clinical picture that involves several organs, including both the peripheral and central nervous systems, is a common presentation of MID. Movement disorders, even isolated ones, are not rare. Cerebellar ataxia is common in myoclonic epilepsy with ragged red fibers (MERFF) due to mutations in the mitochondrial transfer RNA (tRNA) lysine gene, in Kearns-Sayre syndrome due to mtDNA deletions, in sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) due to nuclear POLG1 gene mutations, and also in ARCA2, Friedreich's ataxia, SPG7, SCA28 and autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) due to mutations in nuclear genes involved in mitochondrial morphology or function. Myoclonus is a key feature of MERFF, but may also be encountered in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), ARCA2, POLG1 mutations and Leigh syndrome. Dystonia is common in Leigh syndrome (which may be caused by 75 different genes) and in Leber hereditary ocular neuropathy (LHON) plus disease, due to mutations in mtDNA genes that encode subunits of NADH dehydrogenase, as well as in ARCA2, pantothenate kinase-associated neurodegeneration (PKAN), mitochondrial membrane protein-associated neurodegeneration (MPAN) and POLG1 mutations. Other movement disorders are rarer (such as parkinsonism, tremor, chorea). Although parkinsonism is more frequent in POLG1 mutations, and myoclonus in MERFF, most movement disorders are found either isolated or combined in numerous MIDs. The presence of associated neurological signs, whether central or peripheral, or of evocative magnetic resonance imaging (MRI) abnormalities (striatal necrosis) should prompt a search for MID. In cases of a particular clinical spectrum (LHON, MERFF, Kearns-Sayre, SANDO, SPG7, ARCA2, ARSACS), a search for the most frequently implicated mutation(s) is recommended. In other cases, muscle biopsies followed by metabolic and genetic studies may be useful for arriving at a diagnosis.
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PMID:Movement disorders in mitochondrial diseases. 2777 46

: Oxidative stress is an imbalance between production and accumulation of oxygen reactive species and/or reactive nitrogen species in cells and tissues, and the capacity of detoxifying these products, using enzymatic and non-enzymatic components, such as glutathione. Oxidative stress plays roles in several pathological processes in the nervous system, such as neurotoxicity, neuroinflammation, ischemic stroke, and neurodegeneration. The concepts of oxidative stress and rare diseases were formulated in the eighties, and since then, the link between them has not stopped growing. The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying some groups of rare diseases: Friedreich's ataxia, diseases with neurodegeneration with brain iron accumulation, Charcot-Marie-Tooth as an example of rare neuromuscular disorders, inherited retinal dystrophies, progressive myoclonus epilepsies, and pediatric drug-resistant epilepsies. Despite the discrimination between cause and effect may not be easy on many occasions, all these conditions are Mendelian rare diseases that share oxidative stress as a common factor, and this may represent a potential target for therapies.
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PMID:Oxidative Stress, a Crossroad Between Rare Diseases and Neurodegeneration. 3232 94