- Email: [email protected]
G.P.26
802
Abstracts / Neuromuscular Disorders 24 (2014) 791–924
G.P.25 Low prevalence of skeletal muscle involvement in patients suffering from idiopathic cardiomyopathy L. Gonza´lez Mera 1, J. Salazar 1, J. Roca 1, L. Gonzalez Quereda 2, P. Gallano 2, F. Martı´nez 1, J. Gonza´lez Costelo 1, M. Olive 1 1 IDIBELL-Hospital Universitari de Bellvitge, Barcelona, Spain; 2 CIBERER U-705, Hospital Sant Pau, Barcelona, Spain Idiopathic cardiomyopathies (ICM) are a group of heterogeneous cardiac diseases that may predispose young patients to sudden cardiac death. They may occur isolated or as a manifestation of a skeletal myopathy, sometimes being the first manifestation of a neuromuscular disease. Involvement of cardiac muscle in patients suffering from ICM may be overlooked, or, sometimes remains poorly defined. We aimed to evaluate the involvement of skeletal muscle in patients diagnosed with ICM. Among a series of 90 patients with ICM we selected 60 patients (sporadic patients presenting before the age of 40, and all familial cases irrespective of the age at the disease onset). We determined serum CK levels, and performed a detailed clinical examination specially focused on the presence of muscle weakness and/or joint retractions. Muscle imaging studies were performed in 49 cases. In 17 cases a genetic analysis was performed using a panel that includes 150 genes involved in familial cardiomyopathies. Results: we have examined 37 patients with dilated CM, 17 with hypertrophic CM, 3 left ventricular noncompaction CM, 2 arrhythmogenic right ventricular dysplasia, and 1 restrictive CM. CK levels were normal in all patients. Mild joint retractions were observed in 10, two of whom also had muscle weakness; two additional patients had isolated muscle weakness. Muscle imaging studies did not show relevant findings except for one patient. Among the patients manifesting muscle weakness and/or joint retractions a pathogenic mutation was identified in 4: LMNA n = 1, DES n = 1, DSP n = 1 and TTN = 1. Molecular analysis in 3 patients is currently in course. No mutations were identified in one patient with Achilles tendon retraction. Conclusions: Skeletal muscle involvement in patients with idiopathic cardiomyopathy is rare and in most cases very subtle. A detailed neurological examination may reveal some abnormalities that not always help to reach a final diagnosis. http://dx.doi:10.1016/j.nmd.2014.06.039
G.P.26 Vitamin D deficiency myopathy in Egypt: A treatable myopathy N.A. Fahmy, D. Fayez Ain Shams University, Cairo, Egypt Vitamin D deficiency could be due to decreased bioavailability (decreased intake or exposure to sunlight, urinary loss or malabsorption), abnormal metabolism (liver disease, renal disease) or abnormal target tissue response (vitamin D resistant or gastrointestinal disorders). Vitamin D deficiency is one of the causes of osteomalacic myopathy. To highlight the clinical and laboratory characteristics of vitamin D deficiency myopathy in Egypt and to discuss its therapeutic implications. All patients presented with gradual progressive limb-girdle weakness with or without bony pains, pains of limb muscles, low backache or joint pains. All patients had detailed clinical assessment, laboratory study (including serum calcium, phosphorus, alkaline phosphatase, total creatine kinase, parathyroid hormone and 25 (OH) vitamin D levels together with neurophysiological study and muscle biopsy in some cases. 30 patients were found to have vitamin D deficiency myopathy. Most of them were females, adolescents or early adults. Decreased dairy intake and decreased exposure to sunlight were the main causes for their illness. Most of them had stereotyped clinical presentation with marked deficiency of serum calcium, increased serum phosphorus and increased alkaline phosphatase levels. Parathyroid hormone serum level was high
and vitamin D serum level was low. Muscle biopsy showed non-specific myopathic changes in studied specimens. Therapy with a combination of daily calcium and vitamin D intake greatly improve both pains and weakness within few months of all patients. Vitamin D deficiency myopathy is a common condition among females in Egypt due to decreased dairy intake and exposure to sunlight. Clinicians must take attention to this type of myopathy as it is a treatable myopathy. http://dx.doi:10.1016/j.nmd.2014.06.040
G.P.27 Latest updates to the MDA monoclonal antibody resource for neuromuscular disorders L.T. Le 1, T.M. Nguyen 2, C.A. Sewry 3, G.E. Morris 1 1 RJAH Orthopaedic Hospital and Keele University, Oswestry, UK; 2 RJAH Orthopaedic Hospital, Oswestry, UK; 3 RJAH Orthopaedic Hospital and ICH, UCL, Oswestry, London, UK Specific antibodies are vital research tools in the fight against neuromuscular disease, but no single antibody can perform all the necessary functions. Over a period of 20 years, we have produced large numbers of well-characterized antibodies for studies of the most common neuromuscular diseases (Duchenne/Becker and Emery-Dreifuss muscular dystrophies, spinal muscular atrophy and myotonic dystrophy). This MDA Monoclonal Antibody (mAb) resource currently contains over 350 different mAbs, including 150 exon-specific dystrophin mAbs. The antibody panels are currently used by the research community (a) for assessing the outcome of gene therapy, cell therapy, drug therapy or oligonucleotide therapy trials (e.g. dystrophin switch-on or alternative splicing) (b) for animal or cellular model systems to look for novel drug treatments (e.g. SMN or utrophin up-regulation) or novel approaches to gene/protein replacement, and (c) for basic research into understanding disease pathogenesis with the eventual aim of discovering novel treatment targets (e.g. muscleblind and msh3 in myotonic dystrophy). All mAbs are freely available for academic research, subject to an agreed form of acknowledgement in any publications. We now describe the most recent additions to the resource, including new mAbs against nebulin and nesprins 1 and 2. Technical advice freely available from the resource, including datasheets and protocols for producing and applying mAbs, will also be presented. The resource website can be found at www.glennmorris.org.uk/mabs.htm. http://dx.doi:10.1016/j.nmd.2014.06.041
G.P.28 Through myotubes normalization, CYTOO 2D+ increase sensitivity of muscle damage HCS assay Y.M. Margaron 1, M. Fernandes 2, D. Morales 2, S. Degot 2 1 CYTOO, 38040, France; 2 CYTOO, Grenoble, France Since classical ADME/Tox tests failed to detect statin drugs family as toxicant by inducing chronic muscle damages such as myositis, rhabdomyolysis, muscle pain; which leaded to a considerable economic burden for pharmaceutical industry, e.g. cerivastatin withdrawal from the market, companies need to develop more relevant in vitro models dedicated to muscle damage drug discovery. In this context, CYTOO developed a physiological muscle model improving the sensitivity of myotoxic drug detection. When cultured on 2D+ technology, primary human myoblasts faster differentiate in myotubes containing a higher level of sarcomere striation and nuclei alignment compared to standard culture condition. Moreover, 2D+ technology standardizes myotubes formation and enables accessing new parameters for myotubes characterization upon drug treatment. Thanks to the development of
Abstracts / Neuromuscular Disorders 24 (2014) 791–924
G.P.25 Low prevalence of skeletal muscle involvement in patients suffering from idiopathic cardiomyopathy L. Gonza´lez Mera 1, J. Salazar 1, J. Roca 1, L. Gonzalez Quereda 2, P. Gallano 2, F. Martı´nez 1, J. Gonza´lez Costelo 1, M. Olive 1 1 IDIBELL-Hospital Universitari de Bellvitge, Barcelona, Spain; 2 CIBERER U-705, Hospital Sant Pau, Barcelona, Spain Idiopathic cardiomyopathies (ICM) are a group of heterogeneous cardiac diseases that may predispose young patients to sudden cardiac death. They may occur isolated or as a manifestation of a skeletal myopathy, sometimes being the first manifestation of a neuromuscular disease. Involvement of cardiac muscle in patients suffering from ICM may be overlooked, or, sometimes remains poorly defined. We aimed to evaluate the involvement of skeletal muscle in patients diagnosed with ICM. Among a series of 90 patients with ICM we selected 60 patients (sporadic patients presenting before the age of 40, and all familial cases irrespective of the age at the disease onset). We determined serum CK levels, and performed a detailed clinical examination specially focused on the presence of muscle weakness and/or joint retractions. Muscle imaging studies were performed in 49 cases. In 17 cases a genetic analysis was performed using a panel that includes 150 genes involved in familial cardiomyopathies. Results: we have examined 37 patients with dilated CM, 17 with hypertrophic CM, 3 left ventricular noncompaction CM, 2 arrhythmogenic right ventricular dysplasia, and 1 restrictive CM. CK levels were normal in all patients. Mild joint retractions were observed in 10, two of whom also had muscle weakness; two additional patients had isolated muscle weakness. Muscle imaging studies did not show relevant findings except for one patient. Among the patients manifesting muscle weakness and/or joint retractions a pathogenic mutation was identified in 4: LMNA n = 1, DES n = 1, DSP n = 1 and TTN = 1. Molecular analysis in 3 patients is currently in course. No mutations were identified in one patient with Achilles tendon retraction. Conclusions: Skeletal muscle involvement in patients with idiopathic cardiomyopathy is rare and in most cases very subtle. A detailed neurological examination may reveal some abnormalities that not always help to reach a final diagnosis. http://dx.doi:10.1016/j.nmd.2014.06.039
G.P.26 Vitamin D deficiency myopathy in Egypt: A treatable myopathy N.A. Fahmy, D. Fayez Ain Shams University, Cairo, Egypt Vitamin D deficiency could be due to decreased bioavailability (decreased intake or exposure to sunlight, urinary loss or malabsorption), abnormal metabolism (liver disease, renal disease) or abnormal target tissue response (vitamin D resistant or gastrointestinal disorders). Vitamin D deficiency is one of the causes of osteomalacic myopathy. To highlight the clinical and laboratory characteristics of vitamin D deficiency myopathy in Egypt and to discuss its therapeutic implications. All patients presented with gradual progressive limb-girdle weakness with or without bony pains, pains of limb muscles, low backache or joint pains. All patients had detailed clinical assessment, laboratory study (including serum calcium, phosphorus, alkaline phosphatase, total creatine kinase, parathyroid hormone and 25 (OH) vitamin D levels together with neurophysiological study and muscle biopsy in some cases. 30 patients were found to have vitamin D deficiency myopathy. Most of them were females, adolescents or early adults. Decreased dairy intake and decreased exposure to sunlight were the main causes for their illness. Most of them had stereotyped clinical presentation with marked deficiency of serum calcium, increased serum phosphorus and increased alkaline phosphatase levels. Parathyroid hormone serum level was high
and vitamin D serum level was low. Muscle biopsy showed non-specific myopathic changes in studied specimens. Therapy with a combination of daily calcium and vitamin D intake greatly improve both pains and weakness within few months of all patients. Vitamin D deficiency myopathy is a common condition among females in Egypt due to decreased dairy intake and exposure to sunlight. Clinicians must take attention to this type of myopathy as it is a treatable myopathy. http://dx.doi:10.1016/j.nmd.2014.06.040
G.P.27 Latest updates to the MDA monoclonal antibody resource for neuromuscular disorders L.T. Le 1, T.M. Nguyen 2, C.A. Sewry 3, G.E. Morris 1 1 RJAH Orthopaedic Hospital and Keele University, Oswestry, UK; 2 RJAH Orthopaedic Hospital, Oswestry, UK; 3 RJAH Orthopaedic Hospital and ICH, UCL, Oswestry, London, UK Specific antibodies are vital research tools in the fight against neuromuscular disease, but no single antibody can perform all the necessary functions. Over a period of 20 years, we have produced large numbers of well-characterized antibodies for studies of the most common neuromuscular diseases (Duchenne/Becker and Emery-Dreifuss muscular dystrophies, spinal muscular atrophy and myotonic dystrophy). This MDA Monoclonal Antibody (mAb) resource currently contains over 350 different mAbs, including 150 exon-specific dystrophin mAbs. The antibody panels are currently used by the research community (a) for assessing the outcome of gene therapy, cell therapy, drug therapy or oligonucleotide therapy trials (e.g. dystrophin switch-on or alternative splicing) (b) for animal or cellular model systems to look for novel drug treatments (e.g. SMN or utrophin up-regulation) or novel approaches to gene/protein replacement, and (c) for basic research into understanding disease pathogenesis with the eventual aim of discovering novel treatment targets (e.g. muscleblind and msh3 in myotonic dystrophy). All mAbs are freely available for academic research, subject to an agreed form of acknowledgement in any publications. We now describe the most recent additions to the resource, including new mAbs against nebulin and nesprins 1 and 2. Technical advice freely available from the resource, including datasheets and protocols for producing and applying mAbs, will also be presented. The resource website can be found at www.glennmorris.org.uk/mabs.htm. http://dx.doi:10.1016/j.nmd.2014.06.041
G.P.28 Through myotubes normalization, CYTOO 2D+ increase sensitivity of muscle damage HCS assay Y.M. Margaron 1, M. Fernandes 2, D. Morales 2, S. Degot 2 1 CYTOO, 38040, France; 2 CYTOO, Grenoble, France Since classical ADME/Tox tests failed to detect statin drugs family as toxicant by inducing chronic muscle damages such as myositis, rhabdomyolysis, muscle pain; which leaded to a considerable economic burden for pharmaceutical industry, e.g. cerivastatin withdrawal from the market, companies need to develop more relevant in vitro models dedicated to muscle damage drug discovery. In this context, CYTOO developed a physiological muscle model improving the sensitivity of myotoxic drug detection. When cultured on 2D+ technology, primary human myoblasts faster differentiate in myotubes containing a higher level of sarcomere striation and nuclei alignment compared to standard culture condition. Moreover, 2D+ technology standardizes myotubes formation and enables accessing new parameters for myotubes characterization upon drug treatment. Thanks to the development of