title: LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.
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.
  
  
  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.
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Musumeci
authors.affiliation: Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Florence, Italy.
authors.forename: G
authors.initials: G
authors.lastname: la Marca
authors.affiliation: Department of Neuroscience, University of Turin, Turin, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Spada
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Mondello
authors.affiliation: University of Pavia, Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Danesino
authors.affiliation: 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.
authors.forename: G P
authors.initials: GP
authors.lastname: Comi
authors.affiliation: Neurological Clinic, University of Padova, Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pegoraro
authors.affiliation: Department of Neurology, Mental Health and Sensory Organs (NESMOS) Faculty of Medicine and Psychology University of Rome "Sapienza", Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Antonini
authors.affiliation: ASP 8, Cagliari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Marrosu
authors.affiliation: IRCCS Istituto di Scienze Neurologiche and Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Liguori
authors.affiliation: Neuroimmunology and Neuromuscular Diseases Unit, Foundation IRCCS Neurological Institute "Carlo Besta", Italy.
authors.forename: L
authors.initials: L
authors.lastname: Morandi
authors.affiliation: Neuromuscular Unit-Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Dino Ferrari Centre University of Milan, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Moggio
authors.affiliation: University of Tor Vergata, Roma, Italy.
authors.forename: R
authors.identifier: http://orcid.org/0000-0001-7523-6956
authors.initials: R
authors.lastname: Massa
authors.affiliation: University of Pavia, Pavia, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ravaglia
authors.affiliation: Centro Malattie Neuromuscolari e Centro Studi sull'Invecchiamento (CeSI), Chieti, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Di Muzio
authors.affiliation: University Hospital Spedali Civili, Neurological Clinic, Brescia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Filosto
authors.affiliation: Neurological Clinic, University of Verona, Verona, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Tonin
authors.affiliation: University of Napoli, Napoli, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Iorio
authors.affiliation: Institute of Neurology, Catholic University, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Servidei
authors.affiliation: Neurological Clinic, University of Pisa, Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: Neurological Clinic, University of Padova, Padova, Italy IRCCS S Camillo, Venice, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Department of Neurosciences 'Rita Levi Montalcini', University of Turin, Turin, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Mongini
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Toscano
mesh_terms: D000328:Adult; D017668:Age of Onset; D003402:Creatine Kinase / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D005470:Fluorometry; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology; D018482:Muscle, Skeletal / Q000473:pathology; D057089:Pathology, Molecular / Q000379:methods; D015203:Reproducibility of Results; D012306:Risk; D053719:Tandem Mass Spectrometry; D000520:alpha-Glucosidases / Q000235:genetics
chemical_list: D003402:Creatine Kinase; C509951:GAA protein, human; D000520:alpha-Glucosidases
keywords: METABOLIC DISEASE; MUSCLE DISEASE