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Research paper
LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population
  1. O Musumeci1,
  2. G la Marca2,
  3. M Spada3,
  4. S Mondello1,
  5. C Danesino4,
  6. G P Comi5,
  7. E Pegoraro6,
  8. G Antonini7,
  9. G Marrosu8,
  10. R Liguori9,
  11. L Morandi10,
  12. M Moggio11,
  13. R Massa12,
  14. S Ravaglia4,
  15. A Di Muzio13,
  16. M Filosto14,
  17. P Tonin15,
  18. G Di Iorio16,
  19. S Servidei17,
  20. G Siciliano18,
  21. C Angelini6,19,
  22. T Mongini20,
  23. A Toscano1,
  24. the Italian GSD II group
    1. 1Department of Neurosciences, University of Messina, Messina, Italy
    2. 2Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Florence, Italy
    3. 3Department of Neuroscience, University of Turin, Turin, Italy
    4. 4University of Pavia, Pavia, Italy
    5. 5Neuroscience 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. 6Neurological Clinic, University of Padova, Padova, Italy
    7. 7Department of Neurology, Mental Health and Sensory Organs (NESMOS) Faculty of Medicine and Psychology University of Rome “Sapienza”, Rome, Italy
    8. 8ASP 8, Cagliari, Italy
    9. 9IRCCS Istituto di Scienze Neurologiche and Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
    10. 10Neuroimmunology and Neuromuscular Diseases Unit, Foundation IRCCS Neurological Institute “Carlo Besta”, Italy
    11. 11Neuromuscular Unit—Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Dino Ferrari Centre University of Milan, Milan, Italy
    12. 12University of Tor Vergata, Roma, Italy
    13. 13Centro Malattie Neuromuscolari e Centro Studi sull'Invecchiamento (CeSI), Chieti, Italy
    14. 14University Hospital Spedali Civili, Neurological Clinic, Brescia, Italy
    15. 15Neurological Clinic, University of Verona, Verona, Italy
    16. 16University of Napoli, Napoli, Italy
    17. 17Institute of Neurology, Catholic University, Rome, Italy
    18. 18Neurological Clinic, University of Pisa, Pisa, Italy
    19. 19IRCCS S Camillo, Venice, Italy
    20. 20Department of Neurosciences ‘Rita Levi Montalcini’, University of Turin, Turin, Italy
    1. Correspondence to Professor Antonio Toscano, Department of Neurosciences, University of Messina, Regional Reference Center for Rare Neuromuscular Disorders, AOU Policlinico “G Martino”, Via C Valeria, Messina 98125, Italy; atoscano{at}unime.it

    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.

    • METABOLIC DISEASE
    • MUSCLE DISEASE

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