title: No cardiomyopathy in X-linked myopathy with excessive autophagy.
abstract: In X-linked myopathy with excessive autophagy (XMEA) progressive sarcoplasmic accumulation of autolysosomes filled with undegraded debris leads to atrophy and weakness of skeletal muscles. XMEA is caused by compromised acidification of lysosomes resulting from hypofunction of the proton pump vacuolar ATPase (V-ATPase), due to hypomorphic mutations in VMA21, whose protein product assembles V-ATPase. To what extent the cardiac muscle is affected is unknown. Therefore we performed a comprehensive cardiac evaluation in four male XMEA patients, and also examined pathology of one deceased patient's cardiac and skeletal muscle. None of the symptomatic men (aged 25-48 years) had history or symptoms of cardiomyopathy. Resting electrocardiograms and echocardiographies were normal. MRI showed normal left ventricle ejection fraction and myocardial mass. Myocardial late-gadolinium enhancement was not detected. The deceased patient's skeletal but not cardiac muscle showed characteristic accumulation of autophagic vacuoles. In conclusion, in classic XMEA the myocardium is structurally, electrically and clinically spared.
authors.affiliation: Heart Center, Turku University Hospital and University of Turku, Turku FI-20520, Finland; PET Centre, Turku University Hospital and University of Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Turku University Hospital, Turku, Finland.
authors.forename: Juha W
authors.initials: JW
authors.lastname: Koskenvuo
authors.affiliation: Heart Center, Turku University Hospital and University of Turku, Turku FI-20520, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Airaksinen
authors.affiliation: Program in Genetics and Genome Biology and Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Nivetha
authors.initials: N
authors.lastname: Ramachandran
authors.affiliation: Program in Genetics and Genome Biology and Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Iulia
authors.initials: I
authors.lastname: Munteanu
authors.affiliation: Folkhälsan Institute of Genetics and Department of Medical Genetics, University of Helsinki, Helsinki, Finland; Neuromuscular Research Unit, Department of Neurology, University Hospital and University of Tampere, Tampere, Finland.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Udd
authors.affiliation: Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Huovinen
authors.affiliation: Department of Pathology, University of Helsinki, Helsinki, Finland; Department of Forensic Medicine, Institute of Biomedicine, University of Turku, Turku, Finland. Electronic address: hannu.kalimo@helsinki.fi.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kalimo
authors.affiliation: Program in Genetics and Genome Biology and Division of Neurology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
mesh_terms: D000328:Adult; D001343:Autophagy / Q000235:genetics; D009202:Cardiomyopathies / Q000150:complications* / Q000175:diagnosis* / Q000503:physiopathology; D004562:Electrocardiography; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000648:ultrastructure; D009135:Muscular Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009154:Mutation; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: C540401:VMA21 protein, human; D025262:Vacuolar Proton-Translocating ATPases
keywords: Autolysosomes; Cardiomyopathy; Danon disease; Electron microscopy; Organellar acidification; X-linked myopathy with excessive autophagy