O Musumeci1, G la Marca2, M Spada3, S Mondello1, C Danesino4, G P Comi5, E Pegoraro6, G Antonini7, G Marrosu8, R Liguori9, L Morandi10, M Moggio11, R Massa12, S Ravaglia4, A Di Muzio13, M Filosto14, P Tonin15, G Di Iorio16, S Servidei17, G Siciliano18, C Angelini19, T Mongini20, A Toscano1. 1. Department of Neurosciences, University of Messina, Messina, Italy. 2. Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Florence, Italy. 3. Department of Neuroscience, University of Turin, Turin, Italy. 4. University of Pavia, Pavia, Italy. 5. Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), Neurology Unit, Dino Ferrari Centre, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 6. Neurological Clinic, University of Padova, Padova, Italy. 7. Department of Neurology, Mental Health and Sensory Organs (NESMOS) Faculty of Medicine and Psychology University of Rome "Sapienza", Rome, Italy. 8. ASP 8, Cagliari, Italy. 9. IRCCS Istituto di Scienze Neurologiche and Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy. 10. Neuroimmunology and Neuromuscular Diseases Unit, Foundation IRCCS Neurological Institute "Carlo Besta", Italy. 11. Neuromuscular Unit-Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Dino Ferrari Centre University of Milan, Milan, Italy. 12. University of Tor Vergata, Roma, Italy. 13. Centro Malattie Neuromuscolari e Centro Studi sull'Invecchiamento (CeSI), Chieti, Italy. 14. University Hospital Spedali Civili, Neurological Clinic, Brescia, Italy. 15. Neurological Clinic, University of Verona, Verona, Italy. 16. University of Napoli, Napoli, Italy. 17. Institute of Neurology, Catholic University, Rome, Italy. 18. Neurological Clinic, University of Pisa, Pisa, Italy. 19. Neurological Clinic, University of Padova, Padova, Italy IRCCS S Camillo, Venice, Italy. 20. Department of Neurosciences 'Rita Levi Montalcini', University of Turin, Turin, Italy.
Abstract
OBJECTIVE: A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. DESIGN/ METHODS: 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. RESULTS: In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. CONCLUSIONS: LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
OBJECTIVE: A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool. DESIGN/ METHODS: 17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis. RESULTS: In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW. CONCLUSIONS: LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Zoltan Lukacs; Paulina Nieves Cobos; Stephan Wenninger; Tracey A Willis; Michela Guglieri; Marc Roberts; Rosaline Quinlivan; David Hilton-Jones; Teresinha Evangelista; Stephan Zierz; Beate Schlotter-Weigel; Maggie C Walter; Peter Reilich; Thomas Klopstock; Marcus Deschauer; Volker Straub; Wolfgang Müller-Felber; Benedikt Schoser Journal: Neurology Date: 2016-05-11 Impact factor: 9.910
Authors: W N Löscher; M Huemer; T M Stulnig; P Simschitz; S Iglseder; C Eggers; H Moser; D Möslinger; M Freilinger; F Lagler; S Grinzinger; M Reichhardt; R E Bittner; W M Schmidt; U Lex; M Brunner-Krainz; S Quasthoff; J V Wanschitz Journal: J Neurol Date: 2017-11-27 Impact factor: 4.849