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P03.2 Bone Health in a cohort of Irish Duchenne Muscular Dystrophy (DMD) patients
S42 P03. Neuromuscular disorders: Muscular distrophies P03.1 Broad complex ventricular tachycardia in association with Bethlem Myoapthy (BM) R.R. Singh1 *, K. Pysden1 , M. Blackburn1 , A.-M. Childs1 . 1 Leeds Teaching Hospital NHS Trust, United Kingdom Background: Mutations in genes coding for extracellular matrix component collagen VI are responsible for a spectrum of muscle diseases. Bethlem Myoapthy is a milder phenotype with involvement of extensor more than flexor proximal muscles, prominent joint contractures and spinal rigidity. Characteristic scarring of the skin and follicultis are also noted. Diaphragmatic involvement can lead to respiratory insufficiency. Cardiac disease is not reported, though both cardiomyopathy and dysrhythmias are seen in other myopathies with a similar phenotype, particularly those associated with mutations in the Lamin A/C gene associated with dilated cardiomyopathy (conduction system disease, CMD1) and myotonic dystrophy. We present the case of a 9 year old girl with confirmed Col VI A3 mutation with 2 episodes of broad complex ventricular tachycardia, requiring cardio version. Case History: 6 yr old girl presented with evidence of mild proximal weakness, distal joint hypermobility and mild spinal rigidity. Her mother had a similar presentation with progressive muscle weakness, joint contractures, scoliosis and marked spinal rigidity. Biopsy changes in mother were not diagnostic. LMNA mutation screen was negative. MR muscles showed characteristic appearance of collagen related dystrophy and genetic testing confirmed mutation in COL6A. At 9 years she had 2 episodes of broad complex tachycardia which initially responded to Amiodarone but required DC Cardioversion on subsequent admission 3 months later. Background ECG was normal. Echocardiogram and cardiac MRscan showed no evidence of cardiomyopathy. Electrophysiological studies revealed no aberrant pathway or inducible arrhythmias and conclusion was that tachycardias were ventricular in origin. She is currently treated with Sotolol, but may require an implantable defibrillator if medical treatment fails. Her mother has no history of cardiac problems or palpitations. Conclusion: Whilst the occurrence of ventricular tachycardia in this girl may be coincidental, cardiac conduction defects are seen in other myopathies with a similar phenotype. Thus, we recommend a low threshold for investigating paroxysmal events in those with collagen related dystrophy. P03.2 Bone Health in a cohort of Irish Duchenne Muscular Dystrophy (DMD) patients N. McSweeney1 *, M.J. Mc Kenna2 , C. McDonnell3 , N. Murphy3 , D. Webb4 , S. van der Kamp5 , M. Kilbane6 , M. O’Keane6 , B.J. Lynch7 . 1The Central Remedial Clinic, Clontarf, Dublin, Ireland, 2 DXA Unit and Metabolism Laboratory, St. Vincent’s University Hospital, Dublin, Ireland, 3 Department of Paediatric Endocrinology, The Children’s University Hospital, Ireland, 4 Department of Paediatric Neurology, Our Lady’s Children’s Hospital, Dublin, Ireland, 5 DXA Unit, St. Vincent’s University Hospital, Dublin, Ireland, 6 Metabolism Laboratory, St. Vincent’s University Hospital, Dublin, Ireland, 7 Department of Paediatric Neurology, The Children’s University Hospital, Dublin, Ireland Objectives: We sought to determine the prevalence of low bone mineral density (BMD) and vitamin D deficiency, and the response to supplementation in DMD. Methods: We measured BMD Z-score at the whole body and spine, serum 25-hydroxyvitamin D (S-25-OHD), serum procollagen type I aminopropeptide (S-PINP) and urine
Poster sessions aminoterminal crosslinked telopeptide of type 1 collagen (UrNTx). Following supplementation with vitamin D (400 800 IU/d) and calcium (500 1000 mg/d), S-25-OHD was repeated. Results are expressed as mean±SD Results: Forty-seven patients were studied aged 11.4±4.3 years; 53% were ambulant; 55% were on glucocorticoids; 21% had a fracture history. BMD was measured in 39 (spine only = 6; whole body only = 4; both = 29) with Z-score <−2.0 in 32% at spine and in 42% at whole body. Non-ambulant compared to ambulant had lower Z-score at spine (P = 0.029) and whole body (P = 0.004), but were not different with respect to either fracture history or steroid therapy. Spine Z-score correlated with age (r=-0.527; P < 0.001), ambulant status (rho = 0.383; P = 0.025) and whole body Z-score (r = 0.452; P = 0.016). Whole body Z-score did not correlate with age or ambulant status. In multiple regression models, age was the sole determinant of spine Z-score (r2=0.32; P = 0.001) and ambulant status was the sole determinant of whole body Z-score (r2=0.20; P = 0.017). S25-OHD was below 30 nmol/L in 38% at baseline and in 5% after supplementation. At baseline, S-PINP was low in 33%, but Ur-NTx was elevated in 100%. Conclusion: Low BMD, vitamin D deficiency, low bone formation and high bone resorption are common in DMD. P03.3 Clinical, biochemical and molecular analysis of patients with chronic subclinical elevation of CK and recurrent hyperCKemia R. Pons1 *, A. Gika1 , K. Kekou2 , N. Vogiatzakis2 , G. Nikas3 , E. Kanavakis4 , P. Manta5 , A. Ribes6 , A. Andreu7 , E. GarciaArumi7 , E. Michelakaki8 , S. Youroukos1 . 1 First department of pediatrics, University of Athens, Agia Sofia hospital Athens, Greece, 2 Department of genetics, University of Athens, Agia Sofia hospital Athens, Greece, 3Agia Sofia hospital Athens, Greece, 4 Pediatrician Department of genetics, University of Athens Agia Sofia hospital, Athens, Greece, 5 Department of Neurology, University of Athens, School of Medicine, Eginition Hospital, Athens, Greece, 6 Seccion ´ de Errores Cong´enitos del Metabolismo Servicio de Bioqu´ımica y Gen´etica Molecular, Hospital Cl´ınic, IDIBAPS, Barcelona, Spain, 7 Unitat de Patologia Mitocondrial, Centre d’Investigacions en Bioqu´ımica i Biologia Molecular, Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona, Spain, 8 Enzymology and cell function laboratory, Institute of child health, Agia Sofia Hospital Athens, Greece Background: Subclinical elevation of muscle enzymes and recurrent episodes of hyperCKemia are not uncommon in clinical practice. The work-up of these patients is often nondiagnostic. There is a need for the development of diagnostic guidelines. Aim of the study: To delineate the clinical, biochemical and molecular basis of patients with chronic subclinical elevation of CK and with recurrent hyperCKemia Methods: Biochemical and metabolic screening, muscle MRI, muscle biopsy and specific enzyme and molecular analysis was performed in 15 patients with subclinical chronic elevation of CK (Group A) and in 10 patients with recurrent episodes of hyperCKemia (Group B). Results: In Group A metabolic screening was non diagnostic. Muscle MRI was abnormal in 2 patients. Molecular studies revealed mutations in the dystrophin gene in 3 patients and in the g-sarcoglycan gene in 2. Muscle biopsy performed in 4 patients was non diagnostic. In Group B, findings on metabolic screening were consistent with fatty acid oxidation defect in 5 patients, myophosphorylase deficiency in 1 and respiratory chain defect in 1. One patient had a mutation in the dystrophin gene. Conclusion: Patients with recurrent episodes of hyperCKemia are more likely to suffer from a metabolic disorder. The yield of metabolic screening is poor in patients with chronic subclinical elevations of CK. Mutations in the dystrohpin
Poster sessions aminoterminal crosslinked telopeptide of type 1 collagen (UrNTx). Following supplementation with vitamin D (400 800 IU/d) and calcium (500 1000 mg/d), S-25-OHD was repeated. Results are expressed as mean±SD Results: Forty-seven patients were studied aged 11.4±4.3 years; 53% were ambulant; 55% were on glucocorticoids; 21% had a fracture history. BMD was measured in 39 (spine only = 6; whole body only = 4; both = 29) with Z-score <−2.0 in 32% at spine and in 42% at whole body. Non-ambulant compared to ambulant had lower Z-score at spine (P = 0.029) and whole body (P = 0.004), but were not different with respect to either fracture history or steroid therapy. Spine Z-score correlated with age (r=-0.527; P < 0.001), ambulant status (rho = 0.383; P = 0.025) and whole body Z-score (r = 0.452; P = 0.016). Whole body Z-score did not correlate with age or ambulant status. In multiple regression models, age was the sole determinant of spine Z-score (r2=0.32; P = 0.001) and ambulant status was the sole determinant of whole body Z-score (r2=0.20; P = 0.017). S25-OHD was below 30 nmol/L in 38% at baseline and in 5% after supplementation. At baseline, S-PINP was low in 33%, but Ur-NTx was elevated in 100%. Conclusion: Low BMD, vitamin D deficiency, low bone formation and high bone resorption are common in DMD. P03.3 Clinical, biochemical and molecular analysis of patients with chronic subclinical elevation of CK and recurrent hyperCKemia R. Pons1 *, A. Gika1 , K. Kekou2 , N. Vogiatzakis2 , G. Nikas3 , E. Kanavakis4 , P. Manta5 , A. Ribes6 , A. Andreu7 , E. GarciaArumi7 , E. Michelakaki8 , S. Youroukos1 . 1 First department of pediatrics, University of Athens, Agia Sofia hospital Athens, Greece, 2 Department of genetics, University of Athens, Agia Sofia hospital Athens, Greece, 3Agia Sofia hospital Athens, Greece, 4 Pediatrician Department of genetics, University of Athens Agia Sofia hospital, Athens, Greece, 5 Department of Neurology, University of Athens, School of Medicine, Eginition Hospital, Athens, Greece, 6 Seccion ´ de Errores Cong´enitos del Metabolismo Servicio de Bioqu´ımica y Gen´etica Molecular, Hospital Cl´ınic, IDIBAPS, Barcelona, Spain, 7 Unitat de Patologia Mitocondrial, Centre d’Investigacions en Bioqu´ımica i Biologia Molecular, Institut de Recerca Hospital Universitari Vall d’Hebron, Barcelona, Spain, 8 Enzymology and cell function laboratory, Institute of child health, Agia Sofia Hospital Athens, Greece Background: Subclinical elevation of muscle enzymes and recurrent episodes of hyperCKemia are not uncommon in clinical practice. The work-up of these patients is often nondiagnostic. There is a need for the development of diagnostic guidelines. Aim of the study: To delineate the clinical, biochemical and molecular basis of patients with chronic subclinical elevation of CK and with recurrent hyperCKemia Methods: Biochemical and metabolic screening, muscle MRI, muscle biopsy and specific enzyme and molecular analysis was performed in 15 patients with subclinical chronic elevation of CK (Group A) and in 10 patients with recurrent episodes of hyperCKemia (Group B). Results: In Group A metabolic screening was non diagnostic. Muscle MRI was abnormal in 2 patients. Molecular studies revealed mutations in the dystrophin gene in 3 patients and in the g-sarcoglycan gene in 2. Muscle biopsy performed in 4 patients was non diagnostic. In Group B, findings on metabolic screening were consistent with fatty acid oxidation defect in 5 patients, myophosphorylase deficiency in 1 and respiratory chain defect in 1. One patient had a mutation in the dystrophin gene. Conclusion: Patients with recurrent episodes of hyperCKemia are more likely to suffer from a metabolic disorder. The yield of metabolic screening is poor in patients with chronic subclinical elevations of CK. Mutations in the dystrohpin