M.P.2.14 Muscle gene expression profile in adult onset acid maltase deficiency

Abstracts / Neuromuscular Disorders 17 (2007) 764–900 centres. The first complaints were muscle weakness in 66% of the cases, muscle weakness and respiratory problems in 18%, respiratory complaints only in 2%. The median age of onset of muscle weakness was 36 years, the median age of diagnosis 44 years. Forty-four percent of patients walk without aid, 36% with aid, 20% use a wheelchair. Thirty-five percent of the population need non-invasive ventilation and 15% invasive ventilation. Twenty percent of cases have been hospitalised because of acute respiratory failure. Approximately half of French patients with late-onset Pompe disease have already been included in the French Registry, including 10 presently treated (ERT) in a compassionate use. We have already collected important epidemiological data on this rare disease, and we expect that this registry will allow to improve follow-up of the patients, and accurate assessment of long-term clinical and cost-effectiveness of orphan drug therapies in the future. doi:10.1016/j.nmd.2007.06.122

M.P.2.14 Muscle gene expression profile in adult onset acid maltase deficiency Musumeci, O. *; Aguennouz, M.; Rodolico, C.; Lanzano, N.; Maio, F.; Cianci, V.; Ciranni, A.; Vita, G.; Toscano, A. University of Messina, Department of Neurosciences, Psychiatry and Anaesthesiology, Messina, Italy Glycogen storage disease type II (GSD II) is an autosomal recessive disorder due to deficiency of the lysosomal enzyme, a-glucosidase (GAA). The adult form is clinically heterogeneous, and may present as a slowly progressive limb-girdle syndrome with or without respiratory distress. Asymptomatic subjects can be incidentally diagnosed because of elevated creatine kinase levels. GSD II muscle biopsies showed great morphological variability ranging from a vacuolar myopathy with high glycogen content to minimal unspecific changes. So far more than 200 mutations in GAA gene have been reported but there are no clear phenotype–genotype correlations. Other conditions such as non-genetic factors and/or modifying genes influence may determine GSD II clinical pattern. The purpose of this study was to investigate muscle gene expression in patients with late-onset acid maltase deficiency. Muscle specimens from 10 GSD II patients and five normal controls were studied. We divided muscle samples in two groups according to pathological features: one group (G1) characterized by a vacuolar myopathy with increased glycogen and a second group (G2) with minimal or absent changes. Microarray experiments were performed using amplified RNA isolated from muscle specimens hybridized in a GeneChip microarrays panel of the whole human Genome containing approximately 44,000 genes. Gene expression analysis revealed an upregulation of transcripts for calcium binding proteins as calmodulin 6, S100 and myosin light-chain kinase in G1. Ion channels family was downregulated in G1, whereas voltage-gated cation channels such as potassium channel, were upregulated in G2. Folding, sorting and degradation protein family genes, such as ubiquitin and proteasomes, were overexpressed in G1. Among the signal transduction family, high espression of Notch genes was found in G1. Our data support the hypothesis that additional genetic factors could play a role in the pathogenesis of GSD II. doi:10.1016/j.nmd.2007.06.123

POSTERS 7 NUCLEAR ENVELOPATHIES G.P.5.01 Inflammatory or ‘congenital myopathy’ type findings in muscle biopsies of patients with LMNA mutations Lubieniecki, F. 1,*; Monges, S. 2; Dubrovsky, A. 3; Stewart-Harris, A. 4; Ruggieri, V. 2; Barroso, F. 5; Espada, G. 6; Ferrea, M. 7; Robertella, M. 7;

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Richard, P. 8; Bonne, G. 9; Romero, N. 10; Guicheney, P. 9; Sacolitti, M. 11; Taratuto, A. 11 1 Hospital Nacional de Pediatrı´a J.P.Garrahan, Pathology, Buenos Aires, Argentina; 2 Hospital Nacional de Pediatrı´a J.P.Garrahan, Neurology, Buenos Aires, Argentina; 3 Instituto de Neurociencias, Fundacion Favaloro, Neurology, Buenos Aires, Argentina; 4 Hospital Dr.Cosme Argerich, Cardiology, Buenos Aires, Argentina; 5 Instituto de Investigaciones Neurologicas – FLENI, Neurophysiology, Buenos Aires, Argentina; 6 Hospital de Nin˜os R.Gutierrez, Rheumathology, Buenos Aires, Argentina; 7 Instituto de Investigaciones Neurologicas – FLENI, Neuropediatrics, Buenos Aires, Argentina; 8 Groupe Hospitalier Pitie´-Salpeˆtrie`re, Unite´ Fonctionnelle cardio et myoge´ne´tique, Paris, France; 9 Groupe Hospitalier Pitie´Salpeˆtrie`re, Inserm,U582, Institut de Myologie, Paris, France; 10 Groupe Hospitalier Pitie´-Salpeˆtrie`re, Inserm,U582, Unite´ de Morphologie NeuroMusculaire, Paris, France; 11 Instituto de Investigaciones Neurologicas – FLENI, Neuropathology, Buenos Aires, Argentina Muscular dystrophy associated to lamin A/C gene (LMNA) mutations is characterized by muscle weakness, joint contractures, dilated cardiomyopathy and arrhythmias. It includes autosomal dominant and rare recessive forms of Emery–Dreifuss as well as limb-girdle muscular dystrophy 1B and dilated cardiomyopathy with conduction system disease. We here report clinical onset, follow up and pathological findings of four cases. Muscle biopsies were studied at 5 years of age for case 1; 6 and 7 1/2 years for case 2, 14 years for case 3, and 31 years for case 4, by histochemical, immunohistochemical and electron microscopy techniques. Three females with similar findings characterized by muscle weakness, elbow and ankle joint contractures, hypotrophy of upper limbs, cervical rigid spine, hyperlordosis/ scoliosis and cardiac involvement. Typical phenotype was disclosed at 11, 14 and 13 years of age, respectively. Case 1 showed inflammatory together with dystrophic changes, case 2 had relatively preserved fascicles, few denervated fibers, perivascular inflammatory infiltration and focal degeneration and regeneration in 1st biopsy and myopathic changes with type 1 atrophy in the 2nd; case 3 showed dystrophic changes with multiple ’lobulated’ fibers. Each patient presented a dominant missense ’de novo’ mutation in LMNA. Case 4, a 31-year-old male, with familial history of cardiac involvement, presented for 4 years a dilated cardiomyopathy with conduction defect and developed weakness and elbow contractures. Biopsy showed type1 atrophy and Z band streaming with myofibrillar changes and molecular analysis identified a non sense mutation in exon 1 of LMNA gene consisting in c.112ins[ACC] del[1]2-124] . In muscular dystrophy with lamin A/C mutations, clinical phenotype should prompt molecular testing, even when the muscle biopsy shows inflammation or features suggestive of a congenital myopathy Collaboration ECOS – SECYT 2003–2005. doi:10.1016/j.nmd.2007.06.124

G.P.5.02 LMNA is responsible for a recognisable form of congenital muscular dystrophy associated with selective axial muscle weakness and progressive course (L-CMD) Quijano-Roy, S. 1,*; Mbieleu, B. 1; Bo¨nnemann, C. 2; Jeannet, P. 3; Colomer, J. 4; Clarke, N. 5; Cuisset, J. 6; Roper, H. 7; De Meirleir, L. 8; D’Amico, A. 9; Ben Yaou, R. 10; Barois, A. 1; Demay, L. 11; Romero, N. 10; Sewry, C. 12; Bertini, E. 9; Ferreiro, A. 10; Muntoni, F. 13; Guicheney, P. 10; Richard, P. 11; Bonne, G. 10; Estournet, B. 1 1 APHP, Raymond Poincare´ Hospital, Paediatrics, Garches, France; 2 The Children’s Hospital of Philadelphia, Neurology, Philadelphia, United States; 3 CHU Vadois, Paediatrics, Lausanne, Switzerland; 4 Sant Joan de Deu Hospital, Paediatric Neurology, Barcelone, Spain; 5 Children’s Hospital at Westmead, Paediatrics and Child Health, Sydney, Australia; 6 Roger Salengro Hospital, Maladies Neuromusculaires de l’Enfant, Lille, France; 7 Birmingham Heartlands Hospital, Child Health, Birmingham, France; 8 Ghent University Hospital, Paediatrics, Gent,