Evaluation of Experienced Clinical Events in Pompe Disease Based on Real-life Data

Abstract

Objective

Pompe disease is a rare lysosomal storage disorder with a wide clinical spectrum ranging from infantile-onset Pompe disease (IOPD) with early severe cardiomyopathy to late-onset Pompe disease (LOPD) with progressive muscle weakness. This study aimed to evaluate clinical features, genotype–phenotype correlations, treatment outcomes, and significant events in a real-life pediatric cohort of Pompe patients.

Methods

We retrospectively analyzed 30 pediatric patients diagnosed with Pompe disease (27 IOPD, 3 LOPD). Demographic, clinical, biochemical, genetic, and radiologic data were collected. Recurrent clinical events were assessed using the Andersen-Gill extension of the Cox model to evaluate the effect of enzyme replacement therapy (ERT).

Results

The median age at diagnosis was 5 (range 20 days to 80 months) months, and consanguinity was present in 83% of cases. IOPD cases predominantly showed hypotonia and cardiac involvement, whereas LOPD cases were asymptomatic or mildly symptomatic, with delayed motor development and increased CK levels. Novel GAA mutations were identified in seven patients. ERT was administered to 24 IOPD patients, leading to improved cardiac function and prolonged survival. Event incidence was significantly lower in the ERT group (HR = 0.06, p < 0.005), despite a longer follow-up. However, 56% of patients—all with IOPD—died during follow-up. Non-muscular findings such as neurogenic bladder in 6.6% (2/30), sensorineural hearing loss in 13.3% (4/30), and white matter abnormalities in 40.9% (9/21) were also documented.

Conclusions

This real-life evidence reinforces the central role of early, individualized ERT and comprehensive multidisciplinary care in altering the natural course of Pompe disease.

Keywords

clinical events - enzyme replacement therapy - genotype–phenotype - IOPD - LOPD - Pompe disease

Informed Consent

A written informed consent for the publication of this manuscript, including identifying images and other personal and clinical details, was obtained from the participants and parents or legal guardians of all participants under the age of 18.

Supplementary Material available at: https://doi.org/10.1055/a-2777-2932.

Publication History

Received: 25 September 2025

Accepted: 19 December 2025

Accepted Manuscript online:
26 December 2025

Article published online:
22 January 2026

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