Myopathie GNE

La myopathie GNE est une maladie neuromusculaire rare et de description relativement récente. Elle touche une population majoritairement d’âge adulte et se transmet selon un mode autosomique récessif. Bien que rare et universelle, elle prévaut dans la communauté juive d’origine perse installée en Israël ou aux États-Unis, dans des populations extrême-orientales (Japon et pays avoisinants) et, plus près de chez nous, en Bulgarie. Elle entraîne une faiblesse musculaire prédominant sur les extrémités (myopathie distale), touchant initialement, et de façon prépondérante, les muscles releveurs de pieds. Le terme générique de myopathie GNE fait désormais consensus et recouvre plusieurs entités précédemment décrites : la myopathie respectant le quadriceps, la myopathie à inclusions autosomique récessive (hIBM), la myopathie distale de type Nonaka (ou DMRV pour distal myopathy with rimmed vacuoles). Cette myopathie est due à un dysfonctionnement du gène GNE codant une enzyme bifonctionnelle, l’UDP-N-acétylglucosamine-2-épimerase/N-acétylmannosamine kinase. Celle-ci intervient à deux niveaux dans la voie métabolique aboutissant à la synthèse de l’acide sialique. L’acide sialique, aussi appelé acide N-acétylneuraminique (Neu5Ac ou NANA en abrégé), est un monosaccharide indispensable à d’autres molécules, protéiques ou lipidiques, nécessitant des résidus sucrés à leur surface pour un bon fonctionnement. La myopathie GNE s’accompagne de lésions histologiques (vacuoles bordées) à l’intérieur des fibres musculaires. Celles-ci sont assez typiques dans un contexte clinique évocateur, mais non spécifiques et inconstantes d’un muscle à l’autre. Le diagnostic positif de la myopathie GNE repose sur la clinique, dont l’imagerie musculaire, et sur les études génétiques. Si des essais thérapeutiques prometteurs se développent actuellement pour pallier le défaut métabolique récemment mis au jour, le traitement de cette myopathie reste pour l’instant purement symptomatique

New Pathways and Therapeutic Targets in Autoimmune Myasthenia Gravis

International audienc

Myopathie GNE :

Malgré un essai de phase II prometteur, l’acide sialique à libération prolongée n’a pas confirmé son efficacité sur une plus large population de patients. Une déception certaine, mais d’autres pistes thérapeutiques restent ouvertes comme évoqué lors des 23e Journées Neuromusculaires à Marseille les 6 et 7 septembre derniers

Effect of build orientation on the manufacturing process and the properties of stereolithographic dental ceramics for crown frameworks

International audienceStatement of problem: Stereolithography (SLA) ceramic crown frameworks are suitable for clinical use, but the impact of SLA build orientation has not been identified.Purpose: The purpose of this in vitro study was to investigate the effect of 3 build orientations on the physical and mechanical properties and the microstructure of SLA alumina dental ceramics.Material and methods: The physical and mechanical properties and microstructures of 3 different oriented SLA alumina ceramics (ZX, ZY, and XY) were evaluated by visual observation, hydrostatic weighing (n=10/group), Weibull analyses (n=30/group), scanning electron microscopy, 3-point flexural strength (n=30/group), fracture toughness (indentation, single-edge-V-notched-beam) (n=4/group), and Vickers hardness (n=15/group) testing. The hydrostatic weighing, 3-point flexural strength, fracture toughness, and Vickers hardness testing data were statistically analyzed (α=.05).Results: The minimum resting period of slurries between the polymerization of 2 layers was shorter for the ZY- and ZX-oriented specimens and increased with the layer surface. The density and Vickers hardness of the SLA-manufactured specimens were similar for all groups (P>.05). The 95% confidence intervals of the Weibull moduli of the ZX- and ZY-oriented specimens were higher than that of the XY-oriented specimens, with no overlap fraction. The ZY-oriented specimens displayed significantly higher 3-point flexural strength (P<.05) and fracture toughness as evaluated by the single-edge-V-notched-beam method than the ZX-oriented specimens (P<.05). They also displayed significantly higher 3-point flexural strength than the XY-oriented specimens (P<.05). The microstructural analysis showed that the texturing was heterogeneous and that the major axis of the large grains of alumina ran parallel to the orientation of the layers.Conclusions: The ZY orientation produced a reliable dental ceramic by SLA, with the shortest general manufacturing time and the highest mechanical strength when the layers were perpendicular to the test load surfac

The diagnostic value of hyperammonaemia induced by the non-ischaemic forearm exercise test

International audienceAims The non-ischaemic forearm exercise test (NIFET) is used as a diagnostic tool for the screening of patients with exercise intolerance and for the diagnosis of various metabolic muscle disorders. The production of lactate and ammonia are generally analysed to guide the diagnosis. The aim of this retrospective study was to determine the level of ammonia rise, which can be suggestive of a muscle disease.Methods This retrospective study involved 1440 patients who underwent NIFET. The clinical files of the patients with hyperammonaemia were methodically studied. Normal values were derived from 60 healthy controls.Results 110 patients with hyperammonaemia were detected. They were classified as either having mild (between 94 and 141 µmol/L) or severe (more than 141 µmol/L) hyperammonaemia. Their diagnosis was studied with respect to the increase in lactate induced by the NIFET.Conclusions Severe postexercise hyperammonaemia, even in the presence of a normal lactate response, is strongly suggestive of a muscle glycogen storage disease. Mild hyperammonaemia in the absence of other abnormalities is most likely non-specific and not indicative of a muscle disease

Generation of human induced pluripotent stem cell lines from five patients with Myofibrillar myopathy carrying different heterozygous mutations in the DES gene

Myofibrillar myopathy (MFM) is a rare genetic disorder characterized by muscular dystrophy that is often associated with cardiac disease. This disease is caused by mutations in several genes, among them DES (encoding desmin) is the most frequently affected. Peripheral blood mononuclear cells from 5 different MFM patients with different DES mutations were reprogrammed into induced pluripotent stem cells (IPSC) using non-integrative vectors. For each patient, one IPSC clone was selected and demonstrated pluripotency hallmarks without genomic abnormalities. SNP profiles were identical to the cells of origin and all the clones have the capacity to differentiate into all three germ layers

High Risk of Fatal and Non-Fatal Venous Thromboembolism in Myotonic Dystrophy

International audienceBackground: The risk of venous thromboembolism (VTE), defined as deep vein thrombosis, pulmonany embolism (PE), or both, in myotonic dystrophy (DM) is unknown. Our objective was to estimate the risk of VTE in DM and its impact on all-cause and cardiovascular mortality. Methods: In 1,148 retrospectively studied adults (592 women) suffering from DM, referred between January 2000 and January 2015, we estimated the cumulative incidence of VTE and proportion of all- cause and cardiovascular deaths, and compared the incidence of VTE with that in patients with other inherited myopathies followed at our center, and with a community-based French population. Results: Among all patients with DM (mean age=40.6#14.3; 592 women), 82 developed VTE over a 10.9-year follow-up (95% CI 2.4 to 14.7), representing a 10.3% cumulative incidence (95% CI 7.8 to 12.7%), and 253 died, 83 of a cardiovascular cause. In patients with DM, the incidence of VTE was higher than a) in 1,662 patients (mean age=39.7+16.2; 989 women) with other inherited myopathies (mean age=39.7+16.2), in whom the cumulative incidence was 2.2% (95% Cl 1.1 to 3.3) and hazard ratio (HR) 4.63 (95% CI 2.63 to 8.18; p<0.0001), and b) in a community-based population with a standardized rate ratio of 7.53 (95% CI 6.02 to 9.28; p<0.0001). VTE was independently predicted by age (HR=1.02; 95% CI 1.00 to 1.04; p=0.041), personal history of VTE (HR=4.71; 95% CI 2.20 to 10.1; p<0.0001), obesity (HR=2.31; 95% CI 1.30 to 4.08; p=0.004), loss of ambulation (HR=4.57;95% C| 2.12 to9.87; p=0.0001) and history of cancer (HR=3.89; 95% CI 1.62 to 9.32; p=0.002). The 26 deaths from PE in patients with DM represented 10.3% of all deaths and 31.3% of cardiovascular deaths. Conclusion: The risk of fatal and non-fatal VTE in patients with DM was high