Late-onset Pompe’s disease in pediatrics: results from an Italian national survey on 38 patients and proposal of a targeted diagnostic algorithm
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Late-onset Pompe's disease (LOPD) is a progressive treatable metabolic myopathy due to partial acid α-glucosidase (GAA) deficiency, with potential onset during the pediatric age. To date, Pompe's disease is not widely included in newborn screening panels, so that clinical suspect remains essential for timely diagnosis and management. Clinical identification of LOPD was shown to be challenging in adult patients, whereas data in children and adolescents are scanty. We conducted an Italian nationwide multicentric survey in order to delineate the characteristics of LOPD in the pediatric population. This prompted us to propose a diagnostic algorithm to facilitate the identification of LOPD in pediatrics. RESULTS: The survey provided information on 38 Italian pediatric patients with a definite biochemical and molecular diagnosis of LOPD firstly suspected based on clinical approach. Nineteen patients (50%) reached medical attention because of clinical symptoms of LOPD (79% within 3 years of age; 21% at 3-18 years of age) and 19 (50%) because of incidental finding of asymptomatic hyperCKemia. All the 38 LOPD patients showed hyperCKemia (56%: range 500-1000 U/l; 18%; range 250-500 U/l; 18% range 1000-2000 U/l; 8% >2000 U/l), almost invariably accompained by concomitant hypertransaminasemia (91%). Main clinical symptoms before 3 years of age were inability to (1) sit at 8 months, (2) walk indipendently at 18 months, and (3) climb stairs at 30 months. Later pediatric presentations (3-18 years of age) were limitation to (1) get up from supine position, (2) perform sport activity, and (3) run. In symptomatic patients, diagnostic latency (i.e. the time interval between clinical onset and diagnosis of LOPD) ranged from < 1 year (58%) to 2-12 years (42%). CONCLUSIONS: Clinical diagnosis of LOPD in pediatrics is challenging in spite of its frequent presentation within 3 years of age. A selective screening by measuring GAA activity on dried blood spot in the two main clinical diagnostic contexts of LOPD in pediatrics - namely (1) age-related myopathic symptoms or (2) asymptomatic hyperCKemia (and hypertransaminasemia) - will likely ensure diagnostic anticipation for those patients not screened for Pompe's disease in the neonatal period.
Authors: Marco Spada, Serena Gasperini, Massimiliano Filosto, Guja Astrea, Beatrice Bracci, Claudio Bruno, Alberto Burlina, Anna Cavallini, Daniela Concolino, Viola Crescitelli, Adele D’Amico, Federica Deodato, Carlo Dionisi-Vici, Maria Alice Donati, Simona Fecarotta, Rita Fischetto, Agata Fiumara, Francesca Furlan, Vincenza Gragnaniello, Damiano Mala, Monica Marica, Francesca Menni, Veronica Pagliardini, Claudia Panicucci, Giancarlo Parenti, Andrea Pession, Federica Ricci, Valentina Rovelli, Michele Sacchini, Filippo Maria Santorelli, Lucia Santoro, Maurizio Scarpa, Roberta Taurisano, Albina Tummolo, Francesco Porta
Institutions: University of Turin, University of Brescia, Fondazione Stella Maris, Istituto Giannina Gaslini, University of Genoa, University of Padua, Don Carlo Gnocchi Foundation, Magna Graecia University, Bambino Gesù Children's Hospital, Meyer Children's Hospital, University of Naples Federico II, Ospedale Pediatrico Giovanni XXIII, University of Catania, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Azienda Ospedaliera G. Brotzu, University of Bologna, University of Milan, Ospedale San Paolo, Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo, Azienda Ospedaliero-Universitaria delle Marche, University of Udine
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,990
Funder: Sanofi
OpenAlex ID: W4416785707