Orphanet Journal of Rare Diseases | Austrian Consensus Study on Pompe Disease Follow-up Assessment

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This study established a national consensus on Pompe disease follow-up assessment through a rigorous Delphi method, providing a systematic and actionable recommendation framework for clinical practice, which holds significant guidance value.

 

Literature Overview

The article titled 'Austrian Pompe Outcome Consensus (APOC): a national Delphi study', published in the journal Orphanet Journal of Rare Diseases, reviews and summarizes the findings of the Austrian Pompe Outcome Consensus (APOC) study. Using the Delphi method across three rounds of expert consultation, this study systematically developed minimum and optional items for follow-up assessments in Pompe disease patients, defining the strength and frequency of recommendations for each assessment. The goal is to optimize individualized treatment and care, while providing an objective reference framework for healthcare payers and health authorities. The study achieved 34 consensus statements covering assessments across multiple systems, including neuromuscular, respiratory, cardiac, imaging, nutrition, and psychological domains. It is currently one of the few Pompe disease follow-up assessment consensus documents compliant with the AGREE II standard. Applicable not only within the Austrian healthcare system, its methodology also provides a transferable model for standardized management in other rare disease fields.

Background Knowledge

Pompe disease, also known as glycogen storage disease type II, is an autosomal recessive disorder caused by pathogenic variants in the GAA gene, leading to deficiency of lysosomal acid alpha-glucosidase and subsequent abnormal glycogen accumulation within lysosomes. The disease exhibits a broad phenotypic spectrum, ranging from infantile-onset rapidly progressive forms (with cardiomyopathy and severe muscle weakness) to late-onset forms (characterized by slowly progressive skeletal and respiratory muscle dysfunction). Respiratory failure is the primary cause of morbidity and mortality, accompanied by axial and limb-girdle muscle weakness, arrhythmias, swallowing difficulties, and severe fatigue, necessitating multidisciplinary, individualized management. Enzyme replacement therapy (ERT) is the current mainstay of treatment, with several drugs already approved, and gene therapy under development. Although regular follow-up assessments have become standard of care—covering core domains such as functional tests, patient-reported outcomes, imaging, and biomarkers—there is no unified consensus on which assessments constitute essential clinical routines versus those with academic relevance only. Moreover, inconsistent monitoring practices across centers may lead to patient confusion, difficulties in cross-center referrals, and challenges in negotiations with insurers. Therefore, establishing an evidence- and expert consensus-based standardized follow-up protocol is crucial for optimizing patient management, evaluating treatment efficacy, and informing healthcare policy. This study fills this critical knowledge gap through a structured Delphi process, providing nationally representative, systematically weighted recommendations for the long-term management of Pompe disease.

 

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Research Methods and Experiment

The study employed a Delphi method, following the AWMF S2k guideline framework, conducted in Austria between September 2023 and May 2024. A steering committee of five interdisciplinary experts from five medical centers invited 18 clinical experts with experience in Pompe disease management to form the expert panel. The study consisted of three rounds: the first two were online surveys in which experts rated the importance and recommended frequency of follow-up assessments; the second round provided anonymous aggregated feedback from the first; the third was a modified meeting where the steering committee discussed and finalized consensus statements based on the first two rounds to prevent information loss due to expert attrition. The questionnaire was developed based on a scoping literature review and expert workshops, with recommendation strength categorized using AGREE II consensus thresholds (>95% for strong consensus, 75–94% for consensus) and AWMF S2k terminology ('should', 'should consider', 'may'). Data were analyzed by the independent institution Salzburg Research to minimize bias.

Key Conclusions and Perspectives

• The study reached 34 consensus statements, providing a systematic and structured recommendation framework for Pompe disease follow-up assessments
• Strongly recommended assessments include: 6-minute walk test (6MWT), timed tests, the pediatric-specific Pompe PEDI scale, muscle strength testing, hand-held dynamometry, Fatigue Severity Scale (FSS), patient-reported outcomes (e.g., R-Pact), seated/lying forced vital capacity (FVC), morphological muscle imaging, pain, and quality of life assessments
• Recommended assessments include: maximal inspiratory/expiratory pressure (MIP/MEP), sleep studies (polysomnography), creatine kinase (CK), antibody titers, swallowing studies, liver ultrasound, hearing tests, speech and oral motor function, physical therapy and rehabilitation, bone density assessment, and psychosocial care for caregivers
• 6MWT, timed tests, and PROMs should be assessed annually in pediatric patients, with 6MWT initiated at the earliest feasible age (recommended by age 12 at latest)
• Seated/lying FVC should be performed 1–2 times per year; MIP/MEP and sleep studies should be considered 1–2 times per year
• Morphological muscle imaging is strongly recommended, whereas lung/diaphragm MRI and muscle MRI are considered optional
• Quality of life assessments (e.g., EQ-5D-5L) should be conducted regularly, and caregiver psychosocial health should be included in patient/caregiver-reported outcome assessments
• The consensus emphasizes the importance of multidisciplinary, individualized management and sets clear recommendation frequencies and clinical indications for different assessment items

Research Significance and Outlook

This study is the first to establish a nationally representative Pompe disease follow-up assessment consensus compliant with the AGREE II standard, providing a clear and actionable guidance framework for clinical practice. It not only helps improve consistency in patient management across medical centers and enhances comparability of patient outcomes, but also offers an objective basis for negotiations with healthcare payers and authorities. The use of the Delphi method and AWMF S2k framework demonstrates how expert consensus can be efficiently and transparently achieved in rare disease fields where resources and evidence are limited.

Looking ahead, this consensus can be maintained as a 'living guideline' with periodic updates to incorporate new treatments (e.g., gene therapy) and assessment methods. Its methodology can be extended to other rare diseases to establish similar standardized management pathways. Additionally, future research could validate the real-world utility of these recommended assessments in predicting disease progression and treatment response, further optimizing monitoring strategies. Ultimately, such consensus efforts will advance precision medicine in Pompe disease and the broader rare disease landscape.

 

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Conclusion

This study systematically established recommended standards for Pompe disease follow-up assessments through a rigorous national Delphi consensus process (APOC). By aggregating expert opinions from major Austrian medical centers and adhering to AGREE II and AWMF S2k standards, consensus was reached on 34 assessment items. The results clarify core follow-up components—including 6-minute walk test, pulmonary function, muscle imaging, and quality of life assessments—along with their recommended frequencies, offering clinicians a practical decision-support tool. The consensus not only optimizes individualized management and treatment monitoring for Pompe patients but also promotes standardization of clinical practice, helping to address clinical and policy challenges arising from inconsistent monitoring. Its structured methodology provides an efficient and reliable model for guideline development in other rare disease fields. Despite limitations such as a limited number of experts and lack of direct patient involvement, this study lays a crucial foundation for the long-term management of Pompe disease, with significant value in improving patient care quality and informing healthcare policy. Future efforts should focus on implementing, validating, and regularly updating the consensus to keep pace with the evolving treatment landscape.

 

Florian B Lagler, Thomas Scherer, Jörg Weber, Martina Huemer, and Wolfgang Löscher. Austrian Pompe Outcome Consensus (APOC): a national Delphi study. Orphanet Journal of Rare Diseases.