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Glycogen storage disease type II (GSDII) caused by lysosomal acid \u03b1\u2010glucosidase (GAA) deficiency is the best\u2010characterised AVM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to investigate the mutational profiling of seven neuromuscular outpatients sharing clinical, myopathological and biochemical findings with AVMs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We applied a diagnostic protocol, recently published by our research group for suspected late\u2010onset GSDII (LO\u2010GSDII), including counting PAS\u2010positive lymphocytes on blood smears, dried blood spot (DBS)\u2010GAA, muscle biopsy histological and immunofluorescence studies, GAA activity assay and expression studies on muscle homogenate, <jats:italic>GAA<\/jats:italic> sequencing, <jats:italic>GAA<\/jats:italic> multiplex ligation\u2010dependent probe amplification (MLPA) and whole exome sequencing (WES).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patients had a limb girdle\u2010like muscular pattern with persistent hyperCKaemia; vacuolated PAS\u2010positive lymphocytes, glycogen accumulation and impaired autophagy at muscle biopsy. Decreased GAA activity was also measured. While <jats:italic>GAA<\/jats:italic> sequencing identified no pathogenic mutations, WES approach allowed us to identify for each patient an unexpected mutational pattern in genes cooperating in lysosomal\u2010autophagic machinery, some of which have never been linked to human diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data suggest that reduced GAA activity may occur in any condition of impaired autophagy and that WES approach is advisable in all genetically undefined cases of autophagic myopathy. Therefore, deficiency of GAA activity and PAS\u2010positive lymphocytes should be considered as AVM markers together with LC3\/p62\u2010positive autophagic vacuoles.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12690","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T09:23:55Z","timestamp":1609752235000},"page":"664-678","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel autophagic vacuolar myopathies: Phenotype and genotype features"],"prefix":"10.1111","volume":"47","author":[{"given":"Filomena","family":"Napolitano","sequence":"first","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences 2nd Division of Neurology Center for Rare Diseases and Inter University Center for Research in Neurosciences University of Campania \"Luigi Vanvitelli\"  Naples Italy"},{"name":"Institute of Genetics and Biophysics \"Adriano Buzzati\u2010Traverso\" National Research 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