Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We looked for the A-->G transition at position 8344 of mtDNA in 150 patients, most of them with diagnosed or suspected mitochondrial disease, to assess the specificity of this mutation for the MERRF phenotype, to define the clinical spectrum associated with the mutation, and to study the relationship between percentage of mutation in muscle and clinical severity. Our results confirm the high correlation between the A-->G transition at position 8344 and the MERRF syndrome, but they also show that this mutation can be associated with other phenotypes, including Leigh's syndrome, myoclonus or myopathy with truncal lipomas, and proximal myopathy. The absence of the mutation in four typical MERRF patients suggests that other mutations in the tRNA(Lys) gene, or elsewhere in the mitochondrial DNA, can produce the same phenotype.
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PMID:Clinical features associated with the A-->G transition at nucleotide 8344 of mtDNA ("MERRF mutation"). 817 May 67

Fourteen patients (10 boys, 4 girls) aged from 4 months to 14 years old were diagnosed with mitochondrial disease based on the clinical manifestations together with abnormal muscle mitochondrial morphologies. Their clinical diagnoses included Leigh syndrome, three; Menkes' syndrome, three; Kearns-Sayre syndrome, two; myoclonic epilepsy with ragged fibres, one; and infant-onset progressive myoclonic epilepsy, one; fatal infantile mitochondrial myopathy, one; fatty acid oxidation defect, two; and myopathy with cardiopathy, one. Organs involved other than muscles included central nervous system, ten; heart, six; eye, two; liver, two; and kidney, two. Clinical manifestations varied to include hypotonia, seizures, myoclonus, mental retardation, nystagmus, ataxia, ptosis, ophthalmoplegia, retinal degeneration, muscle atrophy, spasticity etc. Nine had an abnormal rise in lactate after glucose loading. Ragged-red fibres were found in four patients. Abnormal mitochondrial morphology included abnormal accumulation, abnormal cristae pattern of tubular, concentric, or parallel form, some contained osmiophilic inclusion bodies. One patient of Leigh syndrome had had brain necropsy which showed intramyelin splitting of myelinated axons.
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PMID:Clinical manifestation of mitochondrial diseases in children. 821 54

We report a patient with isolated familial hypomagnesaemia with hypocalciuria, a rare congenital disorder of magnesium metabolism. During adolescence the patient developed neurological and ophthalmological features not hitherto reported in this condition, including seizures, myoclonus, and retinal pigmentary degeneration. These suggested the phenotype of mitochondrial disease, which has been occasionally reported in association with hypomagnesaemia, but subsequent investigations of mitochondrial function were normal. The pathogenesis of this unusual neurological and ophthalmological syndrome therefore remains uncertain.
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PMID:Isolated familial hypomagnesaemia with novel neurological features: causal link or chance concurrence? 1155 16

Congenital disorders of glycosylation (CDG) and mitochondrial diseases are multisystem disorders with clinical characteristics that may overlap. We present four patients with CDG whose phenotypes suggested the diagnosis of a mitochondrial disease. Patients 1 and 2 are siblings with hemiplegic headache, stroke-like episodes, lactic acidaemia and history of maternal migraine; their initial clinical diagnosis was MELAS syndrome (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes). Patient 3 suffers from ataxia, neuropathy, ophtalmoplegia and retinitis pigmentosa suggestive of NARP (neuropathy, ataxia, and retinitis pigmentosa) syndrome. Patient 4 presented with neurological regression mimicking Leigh disease, with ptosis, myoclonus, ataxia and brainstem and cerebellar atrophy. Screening for mitochondrial disease including enzyme and mtDNA investigations on muscle biopsy were performed on Patients 1, 2 and 4 with normal results. However, evidence for a glycosylation disorder was substantiated by an increased carbohydrate deficient transferrin (CDT). The isoelectric focussing pattern of serum sialotransferrin was typical of CDG type I in Patients 1, 2 and 3 and was shifted towards the less sialylated bands in case 4. A deficiency of phosphomanomutase (PMM) confirmed the diagnosis of CDG-Ia in Patients 1, 2 and 3, who are compound heterozygous for mutations R141H/T237M (Patients 1 and 2) and R141H/P113L (Patient 3). In Patient 4, PMM activity was normal, and further enzymatic and molecular studies are underway. As the search for the primary defect in mitochondrial diseases is often unsuccessful, the pool of mitochondrial patients that remain without definite diagnosis might include CDG cases. Routine screening for CDG may avoid precocious invasive investigations.
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PMID:Congenital disorders of glycosylation (CDG) may be underdiagnosed when mimicking mitochondrial disease. 1158 67

Levetiracetam is a relatively new antiepileptic drug, which has been reported to have promising antimyoclonic properties, especially in posthypoxic myoclonus, progressive myoclonic epilepsy (PME) and spinal myoclonus. Eight patients with intractable myoclonus of various etiologies were given levetiracetam as add-on therapy in an open-label trial. Physician and patient self-assessments were recorded over 1 year. Symptomatic improvement occurred only with posthypoxic myoclonus, which was rapid, dramatic and sustained. All other forms of myoclonus either did not improve or worsened (1 essential myoclonus, 2 myoclonus-dystonia, 2 PME, 2 mitochondrial disease). Levetiracetam has promising but selective antimyoclonic potential, which should be the subject of further study.
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PMID:Limited efficacy of levetiracetam on myoclonus of different etiologies. 1573 75

Corneal clouding is uncommon in infants and children but when present in this age group, it is often associated with mucopolysaccharidoses or Fabry disease. This report describes the case of an 11-year-old male who demonstrated poor weight gain, short stature, segmental myoclonus, and learning problems from 5 years of age followed by general weakness and extremely poor balance. Corneal clouding was evident as a result of a blurred vision complaint at 9 years of age. Both urine metabolic screening for mucopolysaccharidoses and analysis of lysosomal enzymes displayed negative findings. Clinical conditions worsened, including ptosis, progressive weakness, and positive Gowers' sign. Oral glucose lactate stimulation test was positive, therefore a muscle biopsy was performed at 11 years of age. Light microscopy of muscle biopsy disclosed abundant ragged red fibers; electron microscopy revealed abnormal mitochondria in terms of tubular cristae, concentrated cristae, stacking cristae, and round granular patterns of inclusion bodies in the matrix. Thus mitochondrial disease was diagnosed. We conclude that mitochondrial disease should be added to the list of differential diagnosis of corneal clouding in children, especially in cases with normal urine metabolic screening for mucopolysaccharidoses or when assays of lysosomal enzymes appear normal.
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PMID:Corneal clouding: An infrequent ophthalmic manifestation of mitochondrial disease. 1676 25

Mitochondrial encephalopathies are a group of diseases that have as their pathogenic basis an alteration of the mitochondrial DNA (mtDNA). The MELAS phenotype (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) has been related to mutation A3243G in approximately 80% of the cases reported. MERRF (epilepsy myoclonus with ragged red fibers) has been related to mutation A8344G and A8566G of tRNA Lys. We report the case of a 7 months-old female with early clinical signs of encephalopathy associated to the A3243G mutation. Laboratory tests showed lactic acidosis and the EEG pattern was compatible with an encephalopathic process. The infant was treated with ACTH during one month, with clinical and electroencephalographic improvements. Currently, she is receiving treatment with B-vitamins, L-Carnitine and urinary alkalizing agents. It is concluded that an analysis of mtDNA must be made in infants who present convulsions, delay in their psychomotor development, lactic acidosis and an EEG pattern compatible with an encephalopathy, to rule out a mitochondrial disease.
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PMID:[Infantile encephalopathy associated with the MELAS A3243G mutation. Case report]. 1759 46

Mitochondrial respiratory chain disorders are relatively common inborn errors of energy metabolism, with a combined prevalence of one in 5000. These disorders typically affect tissues with high energy requirements, and cerebral involvement occurs frequently in childhood, often manifesting in seizures. Mitochondrial diseases are genetically heterogeneous; to date, mutations have been reported in all 37 mitochondrially encoded genes and more than 80 nuclear genes. The major genetic causes of mitochondrial epilepsy are mitochondrial DNA mutations (including those typically associated with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS] and myoclonic epilepsy with ragged red fibres [MERRF] syndromes); mutations in POLG (classically associated with Alpers syndrome but also presenting as the mitochondrial recessive ataxia syndrome [MIRAS], spinocerebellar ataxia with epilepsy [SCAE], and myoclonus, epilepsy, myopathy, sensory ataxia [MEMSA] syndromes in older individuals) and other disorders of mitochondrial DNA maintenance; complex I deficiency; disorders of coenzyme Q(10) biosynthesis; and disorders of mitochondrial translation such as RARS2 mutations. It is not clear why some genetic defects, but not others, are particularly associated with seizures. Epilepsy may be the presenting feature of mitochondrial disease but is often part of a multisystem clinical presentation. Mitochondrial epilepsy may be very difficult to manage, and is often a poor prognostic feature. At present there are no curative treatments for mitochondrial disease. Individuals with mitochondrial epilepsy are frequently prescribed multiple anticonvulsants, and the role of vitamins and other nutritional supplements and the ketogenic diet remain unproven.
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PMID:Mitochondrial disease and epilepsy. 2228 95

Multiple Symmetrical Lipomatosis (MSL) is an unusual disorder characterized by the development of axial lipomas in adulthood. The pathoetiology of lipoma tissue in MSL remains unresolved. Seven patients with MSL were followed for a mean period of 12 years (8-20 years). All patients had cervical lipomas ranging from subtle lesions to disfiguring masses; six patients had peripheral neuropathy and five had proximal myopathy. Myoclonus, cerebellar ataxia and additional lipomas were variably present. All patients showed clinical progression. Muscle histopathology was consistent with mitochondrial disease. Five patients were positive for mtDNA point mutation m.8344A>G, three of whom underwent lipoma resection--all samples were positive for uncoupling protein-1 mRNA (unique to brown fat). Lipoma from one case stained positive for adipocyte fatty-acid protein-2 (unique to brown fat and immature adipocytes). This long-term study hallmarks the phenotypic heterogeneity of MSL's associated clinical features. The clinical, genetic and molecular findings substantiate the hypothesis that lipomas in MSL are due to a mitochondrial disorder of brown fat.
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PMID:Multiple Symmetrical Lipomatosis--a mitochondrial disorder of brown fat. 2352 50

Myoclonic epilepsy with red ragged fibres (MERRF) is a rare mitochondrial disorder presenting with progressive myoclonus, epilepsy, and cognitive decline. Here, the authors present a case of a 29-year-old lady presenting with myoclonus and describe the subsequent investigations that led to a diagnosis of MERRF. In addition, we examine her cognitive decline over a 9-year period, demonstrating a feature commonly seen in mitochondrial cytopathies.
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PMID:A 29-year-old female with progressive myoclonus and cognitive decline. 2366 23


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