caa a22 4500 445810955 CHVBK 20180317145211.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00415-011-6055-4 doi (NATIONALLICENCE)springer-10.1007/s00415-011-6055-4 The phenotypic spectrum of neutral lipid storage myopathy due to mutations in the PNPLA2 gene [Elektronische Daten] [Peter Reilich, Rita Horvath, Sabine Krause, Nicolai Schramm, Doug Turnbull, Michael Trenell, Kieren Hollingsworth, Grainne Gorman, Volkmar Hans, Jens Reimann, Andrée MacMillan, Lesley Turner, Annette Schollen, Gregor Witte, Birgit Czermin, Elke Holinski-Feder, Maggie Walter, Benedikt Schoser, Hanns Lochmüller] Neutral lipid storage disease is caused by mutations in the CGI-58 or the PNPLA2 genes. Lipid storage can be detected in various cell types including blood granulocytes. While CGI-58 mutations are associated with Chanarin-Dorfman syndrome, a condition characterized by lipid storage and skin involvement (ichthyosis), mutations in the patatin-like phospholipase domain-containing protein 2 gene (PNPLA2) were reported with skeletal and cardiac muscle disease only. We describe clinical, myopathological, magnetic resonance imaging (MRI), and genetic findings of six patients carrying different recessive PNPLA2 mutations. Pulse-chase labeling of control and patient cells with supplementation of clenbuterol, salmeterol, and dexamethasone was performed invitro. The patients share a recognizable phenotype with prominent shoulder girdle weakness and mild pelvic girdle and distal muscle weakness, with highly elevated creatine kinase (CK) and cardiomyopathy developing at later stages. Muscle histology invariably reveals massive accumulation of lipid droplets. New muscle or whole-body MRI techniques may assist diagnosis and may become a useful tool to quantify intramuscular lipid storage. Four novel and two previously reported mutations were detected, affecting different parts of the PNPLA2 gene. Activation of hormone-sensitive lipase by beta-adrenergic substances such as clenbuterol appears to bypass the enzymatic block in PNPLA2-deficient patient cells invitro. PNPLA2 deficiency is a slowly progressive myopathy with onset around the third decade. Cardiac involvement is relatively common at a later stage. Muscle MRI may detect increased lipid in a characteristic distribution, which could be used for monitoring disease progression. Beta-adrenergic agents may be beneficial in improving triacylglycerol breakdown in patients with PNPLA2 mutations. Springer-Verlag, 2011 Neutral lipid storage myopathy (NLSDM) nationallicence PNPLA2 nationallicence Treatment nationallicence Reilich Peter Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut Horvath Rita Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut Krause Sabine Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut Schramm Nicolai Department of Clinical Radiology, Ludwig-Maximilians University, Munich, Germany aut Turnbull Doug Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut Trenell Michael Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut Hollingsworth Kieren Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK aut Gorman Grainne Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut Hans Volkmar Institute of Neuropathology, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany aut Reimann Jens Department of Neurology, University Hospital Bonn, Bonn, Germany aut MacMillan Andrée Provincial Medical Genetics Program, Memorial University, St John's, NL, Canada aut Turner Lesley Provincial Medical Genetics Program, Memorial University, St John's, NL, Canada aut Schollen Annette Institute of Clinical Chemistry, Ludwig-Maximilians University, Munich, Germany aut Witte Gregor Department of Biochemistry, Gene Center, Center for Integrated Protein Sciences and Munich Center for Advanced Photonics, Ludwig-Maximilians University, Munich, Germany aut Czermin Birgit Medical Genetic Centre, Munich, Germany aut Holinski-Feder Elke Medical Genetic Centre, Munich, Germany aut Walter Maggie Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut Schoser Benedikt Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut Lochmüller Hanns Institute of Genetic Medicine, Newcastle University, Central Parkway, NE1 3BZ, Newcastle upon Tyne, UK aut Journal of Neurology Springer-Verlag 258/11(2011-11-01), 1987-1997 0340-5354 258:11<1987 2011 258 415 https://doi.org/10.1007/s00415-011-6055-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00415-011-6055-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Reilich Peter Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut NATIONALLICENCE 700 1- Horvath Rita Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut NATIONALLICENCE 700 1- Krause Sabine Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut NATIONALLICENCE 700 1- Schramm Nicolai Department of Clinical Radiology, Ludwig-Maximilians University, Munich, Germany aut NATIONALLICENCE 700 1- Turnbull Doug Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut NATIONALLICENCE 700 1- Trenell Michael Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut NATIONALLICENCE 700 1- Hollingsworth Kieren Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK aut NATIONALLICENCE 700 1- Gorman Grainne Mitochondrial Research Group, Institute of Ageing and Health, Newcastle University, Newcastle upon Tyne, UK aut NATIONALLICENCE 700 1- Hans Volkmar Institute of Neuropathology, Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany aut NATIONALLICENCE 700 1- Reimann Jens Department of Neurology, University Hospital Bonn, Bonn, Germany aut NATIONALLICENCE 700 1- MacMillan Andrée Provincial Medical Genetics Program, Memorial University, St John's, NL, Canada aut NATIONALLICENCE 700 1- Turner Lesley Provincial Medical Genetics Program, Memorial University, St John's, NL, Canada aut NATIONALLICENCE 700 1- Schollen Annette Institute of Clinical Chemistry, Ludwig-Maximilians University, Munich, Germany aut NATIONALLICENCE 700 1- Witte Gregor Department of Biochemistry, Gene Center, Center for Integrated Protein Sciences and Munich Center for Advanced Photonics, Ludwig-Maximilians University, Munich, Germany aut NATIONALLICENCE 700 1- Czermin Birgit Medical Genetic Centre, Munich, Germany aut NATIONALLICENCE 700 1- Holinski-Feder Elke Medical Genetic Centre, Munich, Germany aut NATIONALLICENCE 700 1- Walter Maggie Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut NATIONALLICENCE 700 1- Schoser Benedikt Friedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians University, Munich, Germany aut NATIONALLICENCE 700 1- Lochmüller Hanns Institute of Genetic Medicine, Newcastle University, Central Parkway, NE1 3BZ, Newcastle upon Tyne, UK aut NATIONALLICENCE 773 0- Journal of Neurology Springer-Verlag 258/11(2011-11-01), 1987-1997 0340-5354 258:11<1987 2011 258 415 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer