المؤلفون: Nathalie Streichenberger, Odile Dubourg, Christophe Vial, Damien Sternberg, Christophe Vandier, Anne-Laure Bedat-Millet, Karine Auré, Anne Lombès, Emmanuel Fournier, Claude Jardel, Frédéric Bouillaud, Valerie Drouin-Garraud, Helene Gervais-Bernard, Philippe Petiot, Bertrand Fontaine, Lucie Clarysse, Pascal Laforêt

المصدر: Neurology. 81:1810-1818

مصطلحات موضوعية: Adult, Male, Mitochondrial DNA, Oxidative phosphorylation, Biology, medicine.disease_cause, MELAS syndrome, DNA, Mitochondrial, Paralyses, Familial Periodic, MELAS Syndrome, medicine, Humans, Cells, Cultured, Sequence Deletion, Genetics, Mutation, Periodic paralysis, Fibroblasts, Mitochondrial Proton-Translocating ATPases, medicine.disease, Molecular biology, Pedigree, Acetazolamide, Phenotype, Lactic acidosis, MT-ATP6, biology.protein, Anticonvulsants, Female, Neurology (clinical), Oxidative stress

الوصف: Objective: To report that homoplasmic deleterious mutations in the mitochondrial DNA MT-ATP6/8 genes may be responsible for acute episodes of limb weakness mimicking periodic paralysis due to channelopathies and dramatically responding to acetazolamide. Methods: Mitochondrial DNA sequencing and restriction PCR, oxidative phosphorylation functional assays, reactive oxygen species metabolism, and patch-clamp technique in cultured skin fibroblasts. Results: Occurrence of a typical MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome in a single member of a large pedigree with episodic weakness associated with a later-onset distal motor neuropathy led to the disclosure of 2 deleterious mitochondrial DNA mutations. The MT-ATP6 m.9185T>C p.Leu220Pro mutation, previously associated with Leigh syndrome, was present in all family members, while the MT-TL1 m.3271T>C mutation, a known cause of MELAS syndrome, was observed in the sole patient with MELAS presentation. Significant defect of complexes V and I as well as oxidative stress were observed in both primary fibroblasts and cybrid cells with 100% m.9185T>C mutation. Permanent plasma membrane depolarization and altered permeability to K + in fibroblasts provided a link with the paralysis episodes. Screening of 9 patients, based on their clinical phenotype, identified 4 patients with similar deleterious MT-ATP6 mutations (twice m.9185T>C and once m.9176T>C or m.8893T>C). A fifth patient presented with an original potentially deleterious MT-ATP8 mutation (m.8403T>C). All mutations were associated with almost-normal complex V activity but significant oxidative stress and permanent plasma membrane depolarization. Conclusion: Homoplasmic mutations in the MT-ATP6/8 genes may cause episodic weakness responding to acetazolamide treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a50eca35318d69dad0a3260a59534f59Test
https://doi.org/10.1212/01.wnl.0000436067.43384.0bTest

المؤلفون: Fabrice Jardin, Jean-Michel Vallat, Didier Hannequin, Annie Laquerrière, Olivier Martinaud, Anne-Laure Bedat-Millet, Lucile Musset, Snejana Jurici

المصدر: Case Reports in Neurology
Case Reports in Neurology, Vol 3, Iss 3, Pp 294-300 (2011)

مصطلحات موضوعية: Waldenström macroglobulinemia, Pathology, medicine.medical_specialty, biology, business.industry, Anti mag, Waldenstrom macroglobulinemia, Autopsy case, Anti-MAG, Amyotrophic lateral sclerosis, medicine.disease, Published: December, 2011, lcsh:RC346-429, Monoclonal gammopathy, nervous system, Immunoglobulin M, Gammopathy, medicine, biology.protein, Neurology (clinical), Antibody, medicine.symptom, business, lcsh:Neurology. Diseases of the nervous system

الوصف: We report the case of a 71-year-old woman with typical signs of bulbar amyotrophic lateral sclerosis (ALS) associated with immunoglobulin M (IgM) monoclonal gammopathy and anti-MAG (myelin-associated glycoprotein) antibodies. This unusual association between ALS and anti-MAG antibodies has previously been reported in a single case. Our present case, at neuropathological examination, demonstrated no causative link between anti-MAG antibodies and ALS.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::862f296793a53acd18d8df1c4b99aad2Test
https://doi.org/10.1159/000335004Test

المؤلفون: Cécile Acquaviva-Bourdain, Bruno Eymard, Odile Boespflug-Tanguy, Isabelle Pénisson-Besnier, Brage S. Andresen, Anne-Laure Bedat-Millet, Anne Lombès, Anthony Behin, Christine Vianey-Saban, Denys Chaigne, Isabelle Delevaux, Michèle Brivet, Cécile Laroche, Pascal Laforêt, Brigitte Chabrol, Odile Rigal

المصدر: laforet, P, Acquaviva-Bourdain, C, Rigal, O, Brivet, M, Penisson-Besnier, I, Chabrol, B, Chaigne, D, Boespflug-Tanguy, O, Laroche, C, Bedat-Millet, A, Behin, A, Delevaux, I, Lombès, A, Andresen, B S, Eymard, B & Vianey-Saban, C 2009, ' Diagnostic assessment and long-term follow-up of 13 patients with Very Long-Chain Acyl-coenzyme A dehydrogenase (VLCAD) deficiency ', Neuromuscular Disorders, vol. 19, pp. 324-329 .

مصطلحات موضوعية: Adult, Male, Heterozygote, medicine.medical_specialty, Mitochondrial Diseases, Adolescent, Genotype, DNA Mutational Analysis, Metabolic myopathy, Exercise intolerance, Biology, Compound heterozygosity, Rhabdomyolysis, Very Long-Chain Acyl-CoA Dehydrogenase Deficiency, Young Adult, Muscular Diseases, Carnitine, Internal medicine, medicine, Humans, Genetic Testing, Child, Beta oxidation, Cells, Cultured, Genetics (clinical), Exercise Tolerance, Muscle Weakness, Acyl-CoA Dehydrogenase, Long-Chain, Homozygote, Acyl CoA dehydrogenase, Middle Aged, medicine.disease, Endocrinology, Neurology, Mutation, Pediatrics, Perinatology and Child Health, biology.protein, Female, Neurology (clinical), medicine.symptom, Differential diagnosis, Biomarkers, Metabolism, Inborn Errors

الوصف: Very Long-Chain Acyl-CoA dehydrogenase (VLCAD) deficiency is an inborn error of mitochondrial long-chain fatty acid oxidation (FAO) most often occurring in childhood with cardiac or liver involvement, but rhabdomyolysis attacks have also been reported in adults. We report in this study the clinical, biochemical and molecular studies in 13 adult patients from 10 different families with VLCAD deficiency. The enzyme defect was demonstrated in cultured skin fibroblasts or lymphocytes. All patients exhibited exercise intolerance and recurrent rhabdomyolysis episodes, which were generally triggered by strenuous exercise, fasting, cold or fever (mean age at onset: 10 years). Inaugural life-threatening general manifestations also occurred before the age of 3 years in four patients. Increased levels of long-chain acylcarnitines with tetradecenoylcarnitine (C14:1) as the most prominent species were observed in all patients. Muscle biopsies showed a mild lipidosis in four patients. For all patients but two, molecular analysis showed homozygous (4 patients) or compound heterozygous genotype (7 patients). For the two remaining patients, only one mutation in a heterozygous state was detected. This study confirms that VLCAD deficiency, although being less frequent than CPT II deficiency, should be systematically considered in the differential diagnosis of exercise-induced rhabdomyolysis. Measurement of fasting blood acylcarnitines by tandem mass spectrometry allows accurate biochemical diagnosis and should therefore be performed in all patients presenting with unexplained muscle exercise intolerance or rhabdomyolysis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88752006eafbb4137e6ba00eac515201Test
https://doi.org/10.1016/j.nmd.2009.02.007Test