Navigating Pompe Disease Assessment: A Comprehensive Scoping Review

Pompe disease (PD) is a rare progressive autosomal recessive disorder resulting from the deficiency of acid alpha-glucosidase (GAA) enzyme activity. Due to its multisystemic involvement, PD leads to significant morbidity and impacts patients' quality of life. Despite the availability of approved disease-modifying treatments, the prompt diagnosis and management of PD, which are crucial for patient outcomes, still present several challenges. This scoping review aimed to synthesize the evidence regarding methods for screening, diagnosing, and following up PD. We searched articles in English and Spanish published from 2017 to February 8, 2022, across 11 databases (i.e., Cochrane Database of Systematic Reviews, Directory of Open Access Journals (DOAJ), Epistemonikos, Ingenta Connect, Medline/PubMed, SAGE, SciELO Citation Index, ScienceDirect, Springer Link, Virtual Health Library, and Wiley Online Library). We included primary studies (i.e., case reports, case series, cross-sectional studies, case controls, cohorts, clinical trials, and qualitative studies), reviews, and guidelines that described at least one assessment method for patients with confirmed clinical, genetic, or biochemical PD. Two independent reviewers screened and extracted data from articles, with a third reviewer solving conflicts. We synthesized data with narrative summaries and descriptive statistics. After screening 2,139 titles and abstracts, we included 96 eligible articles. Cross-sectional studies (n = 30) and guidelines (n = 1) were the most and least prevalent designs, respectively. Most studies targeted late-onset PD (LOPD, n = 48) and infantile-onset PD (IOPD, n = 21). Eleven articles described newborn screening programs, highlighting their potential to improve PD prevalence estimations and still limited availability among countries. Overall, 81 articles documented clinical manifestations of PD. Hypotonia (n = 7) and hypertrophic cardiomyopathy (n = 7) were the most documented for IOPD, while progressive muscle weakness (n = 21) and dyspnea (n = 11) were the most prevalent for LOPD. We found 26 articles reporting biochemical assays, with dried blood spots (DBS) for GAA enzyme deficiency detection being the most cited (n = 19). We also noted a lack of standardization in documenting DBS results. Additionally, 21 articles mentioned genetic studies, with next-generation sequencing emerging as the gold standard for identifying mutated alleles. Functional studies were the most utilized to follow up with patients. However, monitoring strategies for pediatric and adult PD lacked consensus, and only one article assessed patients' quality of life. This review comprehensively evaluated the literature on PD screening, diagnosis, and follow-up methods, identifying prevalent techniques within each assessment category. We emphasized the need for a more standardized approach to reporting biochemical assays, genetic testing, and clinical presentations. Our review also underscored the critical lack of standardization in PD follow-up. Addressing these gaps will enhance the comparability of future research findings and improve the quality of PD-related healthcare. Limitations of this review included restricting eligible languages and publication years to the latest five, the methodological heterogeneity of selected articles, and the lack of individual study bias assessment.