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X-linked myopathy with excessive autophagy (XMEA) linked to the VMA21 gene leads to autophagy failure with progressive vacuolation and atrophy of skeletal muscles. Current knowledge of this rare disease is limited. Our objective was to define the clinical, radiological and natural history of XMEA. We conducted a retrospective study collecting clinical, genetic, muscle imaging and biopsy data of XMEA patients followed in France and reviewed the literature for additional cases. Eighteen males had genetically confirmed VMA21 -linked XMEA in France, in 94.4% of patients due to splicing variants. Mean age at disease onset was 9.4±9.9 (range 1-40) years. In 14/18 patients (77.8%) onset occurred during childhood (<15 years), however in four patients the disease started in adulthood. Patients had anterior and medial compartment thigh muscle weakness, distal contractures (56.3%), elevated CK levels (1287.9±757.8 U/l) and autophagic vacuoles with sarcolemmal features on muscle histopathology. Muscle MRI (n=10) showed a characteristic pattern of lower limb muscle involvement. On follow-up, mean change of functional outcomes was 0.5±1.2 points for Brooke and 2.2±2.5 points for Vignos score, 7/16 patients (43.8%) needed a walking aid and 3/16 (18.8%) were wheelchair-bound. The variant c.164-7T>G was associated with a later onset of symptoms and milder phenotype. Respiratory insufficiency was common (57.1%) but cardiac involvement rare (12.5%). This is the largest study of XMEA disease. Patients show a variable age of onset, but a characteristic clinical, histopathological and muscle imaging presentation, guiding the diagnosis. Although slowly, motor disability progresses with time, and we show that respiratory insufficiency is a feature of the disease. Relevant genotype-phenotype correlations like the presence of the c.164-7T>G variant will help design future clinical trials. [ABSTRACT FROM AUTHOR]

Résumé Introduction Les dermatomyosites sont des pathologies auto-immunes rares. La découverte de nouveaux anticorps spécifiques des dermatomyosites a permis de faire émerger des sous-groupes de patients, parmi eux, les anticorps anti-TIF1γ, les anti-SAE1/2 et les anti-NXP2. Le développement récent de kits de dosage de routine pour la détection de ces auto-anticorps, basés sur la technique d'immunodot, est une avancée dans le diagnostic des dermatomyosites. Toutefois, le partage d'expérience sur les difficultés de l'interprétation des immunodots est indispensable. Nous rapportons ici le profil clinique des patients chez lesquels ces auto-anticorps ont été retrouvés entre 2014 et 2017 au CHU de Bordeaux, et discutons de la fréquence et des causes potentielles de positivité non associées à un contexte clinique de dermatomyosite. Méthodes Cette étude monocentrique et rétrospective a été menée de novembre 2014 à février 2017 au CHU de Bordeaux. Tous les patients porteurs d'anticorps anti-TIF1γ, anti-SAE1/2 et anti-NXP2, détectés par immunodot, ont été inclus. Résultats Cinquante-huit patients ont été inclus : 10 avaient une authentique dermatomyosite et 48 ont été considérés comme des faux positifs. Les 7 patients atteints de dermatomyosites à anti-TIF1γ étaient porteurs d'une néoplasie et, au terme du recueil, seule une patiente était en vie. Sur les 48 faux positifs, 30 patients étaient atteints d'une maladie auto-immune ou inflammatoire et 39 patients présentaient une dysimmunité significative. Aucun de ces patients n'a développé de dermatomyosite au cours du suivi. Conclusion Notre immunodot a permis le diagnostic de 10 nouvelles dermatomyosites. En revanche, le nombre important de faux positifs soulève le problème des performances des immunodots et incitent à un dialogue précoce avec les biologistes devant les difficultés d'interprétation potentiellement rencontrées. Abstract Introduction Dermatomyositis are rare autoimmune diseases. The discovery of specific antibodies such as the anti-TIF1γ, anti-SAE1/2 and anti-NXP2 antibodies has been associated with specific clinical phenotypes. The recent development of standardized kits based on immunodot method is a progress in dermatomyositis diagnosis. Here, we report the clinical characteristics of patients carrying these antibodies with or without clinical setting of dermatomyositis. Methods This single-center french retrospective study was conducted from November 2014 to February 2017 at Bordeaux university hospital. Patients carrying anti-TIF1γ, anti-SAE1/2 and anti-NXP2 antibodies, detected by immunodot, were included. Results Among the 58 patients included, only 10 were finally diagnosed with dermatomyositis. Some form of cancer was found in all anti-TIF1γ antibodies positive patients associated with dermatomyositis. Among the 48 anti-TIF1γ, anti-SAE1/2 and anti-NXP2 antibodies positive patients without clinical phenotype of dermatomyositis, 30 had autoimmune or inflammatory condition and 39 patients presented a significant biological autoimmunity. None of them developed dermatomyositis during the follow-up. Conclusion The immunodot kit allowed the diagnosis of 10 dermatomyositis. A high number of autoantibody positive patients without dermatomyositis raises the issue of the immunodot's performances in the context of biological autoimmunity. [ABSTRACT FROM AUTHOR]