Orphanet Journal of Rare Diseases | Italian National Survey Reveals Clinical Features and Diagnostic Strategies of Late-onset Pompe Disease in Pediatric Patients

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This study systematically analyzed the clinical and biochemical characteristics of 38 pediatric patients with late-onset Pompe disease (LOPD) in Italy and proposed a practical diagnostic algorithm to improve early detection and diagnosis rates.

 

Literature Overview
This article, titled 'Clinical Features and Diagnostic Approach of Late-onset Pompe Disease in Pediatric Patients', published in the Orphanet Journal of Rare Diseases, summarizes clinical and biochemical data from 38 pediatric LOPD patients across Italy. It also proposes a diagnostic workflow aimed at improving the efficiency of diagnosis. The study highlights that even when the disease manifests before the age of 3, diagnostic delays are still significant, and asymptomatic patients are often diagnosed incidentally through elevated creatine kinase (CK) levels.

Background Information
Pompe disease is a lysosomal glycogen storage disorder caused by a deficiency in acid alpha-glucosidase (GAA), categorized into infantile-onset and late-onset forms (LOPD). LOPD can present in childhood but is often misdiagnosed or diagnosed late due to diverse and non-specific clinical manifestations. Since Pompe disease is not yet widely included in newborn screening programs, clinical recognition remains the primary diagnostic approach. Although newborn screening effectiveness has been reported in various populations, real-world data on pediatric patients remain limited. This study, based on a nationwide multi-center survey in Italy, systematically analyzed the clinical and biochemical features of LOPD in children and proposed a targeted diagnostic workflow to enhance early detection, particularly in regions lacking newborn screening programs.

 

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Study Methods and Design
Between January and March 2022, the research team conducted a nationwide survey across 18 metabolic disease centers in Italy, including 38 confirmed LOPD patients. All cases were confirmed via enzymatic and molecular genetic testing for GAA gene mutations. A standardized questionnaire was designed to retrospectively collect data on age at onset, age at diagnosis, gender, and clinical or biochemical features. The findings were used to develop a diagnostic workflow to assist pediatricians in identifying LOPD in routine clinical practice.

Key Findings and Insights

• Among the 38 LOPD patients, 50% sought medical attention due to muscle weakness, while the other 50% were diagnosed incidentally through persistently elevated CK levels during routine exams.
• Of the symptomatic patients, 79% showed clinical manifestations before age 3, and 21% between ages 3 and 18.
• All patients exhibited elevated CK levels, with most also showing mild transaminitis.
• Diagnostic delays ranged from 2 to 12 years, even when symptoms appeared early.
• The research team proposed a diagnostic algorithm, recommending GAA enzyme activity testing when myopathy symptoms, persistent high CK, or elevated transaminases are observed.

Significance and Future Directions
This study is the first systematic description of the clinical and biochemical features of pediatric LOPD patients in Italy. It emphasizes the importance of clinical recognition for early diagnosis in countries without newborn screening programs. The proposed diagnostic workflow has the potential to enhance LOPD detection efficiency, optimize treatment timing, and serve as a reference for future multinational epidemiological studies. As Pompe disease screening is gradually incorporated into newborn screening programs, this study offers practical guidance for clinical management during the transition period.

 

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Conclusion
Through a nationwide survey of 38 pediatric patients with late-onset Pompe disease in Italy, this study revealed the clinical and biochemical features of the disease in childhood and proposed a practical diagnostic workflow. It was found that nearly half of the patients experienced diagnostic delays due to mild or non-specific symptoms, even when onset occurred before age 3. The other half were diagnosed through elevated CK levels detected during routine physical exams, highlighting the critical role of biochemical abnormalities in disease recognition. The research team emphasized the need for systematic GAA enzyme activity screening in routine pediatric practice, especially when myopathy symptoms, persistently elevated CK, or transaminitis occur. This diagnostic algorithm is expected to improve early detection rates of LOPD globally, particularly in regions without widespread newborn screening. Furthermore, as Pompe disease screening becomes more integrated into newborn screening programs, this study provides valuable insights for clinical management and genetic counseling during the transition period.

 

Marco Spada, Serena Gasperini, Massimiliano Filosto, Albina Tummolo, and Francesco Porta. Late-onset Pompe's disease in pediatrics: results from an Italian national survey on 38 patients and proposal of a targeted diagnostic algorithm. Orphanet Journal of Rare Diseases.