Gastrointestinal manifestations and enzyme replacement therapy in late-onset Pompe disease: insights from a cross-sectional analysis

TL;DR

This study explores how gastrointestinal symptoms in late-onset Pompe disease are affected by enzyme replacement therapy and other factors like income and treatment dosage.

Contribution

The study provides new insights into the impact of ERT dosage and socioeconomic factors on GI symptoms in late-onset Pompe disease.

Findings

Standard-dose ERT significantly reduces GI symptoms compared to lower doses or no treatment.

Longer ERT duration correlates with increased constipation severity.

Lower income and respiratory involvement are linked to more severe GI symptoms.

Abstract

Late-onset Pompe disease (LOPD) is an autosomal-recessive disorder caused by acid α-glucosidase (GAA) deficiency, typically presenting after the first year of life and resulting in systemic glycogen accumulation. Beyond motor and respiratory manifestations, gastrointestinal (GI) symptoms have been increasingly reported. Although enzyme replacement therapy (ERT) improves skeletal and respiratory function, its impact on GI symptoms remains unclear.

There were 124 LOPD patients recruited to complete the Gastrointestinal Symptom Rating Scale (GSRS), together with questionnaires on clinical manifestations and demographic data. Spearman’s correlation and multiple linear regression were used to analyze the factors associated with GI symptoms.

In this cross-sectional study, patients receiving standard-dose ERT (20 mg/kg, biweekly) exhibited the mildest GI symptoms compared with untreated patients and those on reduced-dose ERT (< 20 mg/kg or < biweekly). Lower family income, reduced ERT dosage, requirement for respiratory support, and tongue hypertrophy or atrophy were associated with more severe GI symptoms. With increasing ERT dose, improvements in scores of halitosis, loose stools, and the dyspepsia domain were most pronounced, and the time to onset of obvious GI symptoms was correspondingly delayed. However, longer ERT duration correlated positively with constipation severity.

GI symptoms in LOPD are influenced by income, involvement of other organs or systems, and treatment-related factors. Standard-dose ERT significantly alleviates abdominal pain, diarrhea, and dyspepsia, but may exacerbate constipation over time. Future studies should explore novel therapeutic strategies to improve GI symptoms and nutritional status in patients with LOPD.

The online version contains supplementary material available at 10.1186/s13023-025-04171-8.

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