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Late-onset Pompe's disease in pediatrics: results from an Italian national survey on 38 patients and proposal of a
Marco Spada1, Serena Gasperini2, Massimiliano Filosto3
1Department of Pediatrics, University of Torino, Torino, Italy.
Insights
Late-onset Pompe disease (LOPD) diagnosis in children is challenging. A proposed screening algorithm for LOPD, based on myopathic symptoms or elevated creatine kinase and transaminase levels, can improve early detection in pediatric patients.
Area of Science:
- Biochemistry
- Genetics
- Pediatric Neurology
Background:
- Late-onset Pompe disease (LOPD) is a progressive, treatable metabolic myopathy caused by partial acid α-glucosidase (GAA) deficiency.
- LOPD can manifest in pediatric patients, but it is not widely included in newborn screening panels, making clinical suspicion crucial for timely diagnosis.
- Data on LOPD characteristics in children and adolescents are limited, highlighting the need for better diagnostic approaches in this population.
Purpose of the Study:
- To delineate the clinical characteristics of LOPD in the pediatric population in Italy.
- To propose a diagnostic algorithm to facilitate the early identification of LOPD in children and adolescents.
- To address the diagnostic challenges associated with LOPD in pediatric patients.
Main Methods:
- A nationwide multicentric survey was conducted in Italy.
- Information was gathered on 38 pediatric patients with a confirmed biochemical and molecular diagnosis of LOPD.
- Patients were identified through clinical suspicion or incidental findings of hyperCKemia.
Main Results:
- Half of the 38 pediatric LOPD patients presented with clinical symptoms, primarily before age 3 (e.g., inability to sit, walk, or climb stairs).
- The other half were diagnosed due to incidental findings of asymptomatic hyperCKemia, often accompanied by hypertransaminasemia (91%).
- Diagnostic latency in symptomatic patients ranged from under 1 year (58%) to 2-12 years (42%).
Conclusions:
- Clinical diagnosis of LOPD in pediatrics remains challenging, despite frequent onset within the first three years of life.
- A selective screening approach measuring GAA activity in dried blood spots for children with myopathic symptoms or unexplained hyperCKemia/hypertransaminasemia is proposed.
- This screening strategy aims to anticipate diagnosis for pediatric patients not identified through neonatal screening programs.
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.
