A Comprehensive Update on Late-Onset Pompe Disease.

Area of Science:

• Genetics and rare diseases
• Metabolic disorders
• Enzyme deficiencies

Background:

• Pompe disease (PD) results from GAA gene mutations, causing acid alpha-glucosidase deficiency.
• It presents as infantile-onset Pompe disease (IOPD) or late-onset Pompe disease (LOPD), differing in onset, severity, and organ involvement.
• LOPD is a multi-systemic condition necessitating a multidisciplinary management approach.

Purpose of the Study:

• To review diagnostic advancements in late-onset Pompe disease (LOPD).
• To critically discuss the benefits and drawbacks of existing and emerging therapies for LOPD.
• To provide insights into future therapeutic strategies for Pompe disease.

Main Methods:

• Comprehensive literature review of diagnostic methods for Pompe disease.
• Analysis of current therapeutic strategies, including enzyme replacement therapy (ERT).
• Evaluation of novel treatment modalities, such as gene therapy.

Main Results:

• Dried blood spot screening for acid alpha-glucosidase activity is a primary diagnostic step.
• Enzyme replacement therapy (ERT) has been available for over 15 years, altering disease progression but with limitations.
• ERT efficacy can decrease over time, and patient responses are variable.

Conclusions:

• Accurate diagnosis of LOPD relies on enzyme activity assessment and genetic confirmation.
• While ERT offers benefits, its long-term efficacy and patient variability present challenges.
• Gene therapy and other novel approaches hold promise for future Pompe disease treatment.