Neurología guideline: Late-onset Pompe disease
By Litha Mfiki
Key updates in the diagnosis and management of late-onset Pompe disease
The 2026 La Sociedad española de Neurología expert consensus statement updates recommendations for the diagnosis, treatment, and follow-up of late-onset Pompe disease (LOPD).1 The guideline reflects over 15 years of experience with enzyme replacement therapy (ERT) and incorporates evidence for newer enzyme therapies, respiratory monitoring strategies, and multidisciplinary care pathways.
Emphasis on early and confirmed diagnosis of LOPD
The guideline recommends dried blood spot (DBS) testing as the preferred initial screening method for patients with suspected LOPD, particularly those presenting with limb-girdle or axial muscle weakness, elevated creatine kinase levels, or respiratory involvement. Reduced enzyme activity on DBS testing should be confirmed with genetic testing.
Additional screening may support diagnosis in selected cases:
- Genetic testing and whole blood analysis: Recommended when standard sequencing does not identify pathogenic variants despite strong clinical suspicion
- Genetic assessment of family members: Recommended for all family members when LOPD has been confirmed
- Muscle magnetic resonance imaging (MRI) and biopsy: Used to evaluate the distribution and severity of muscle involvement
- Computed tomography (CT), magnetic resonance angiography (MRA), electrocardiography, and echocardiography: Used for assessment of potential rare vascular abnormalities and cardiac arrhythmias
Structured assessment of respiratory involvement in LOPD
Respiratory muscle weakness remains a major contributor to morbidity and mortality in LOPD. The guideline recommends pulmonology assessment from the time of diagnosis, regardless of symptoms.
Initial respiratory evaluation includes:
- Seated and supine forced vital capacity
- Maximal inspiratory and expiratory pressures
- Sniff nasal inspiratory pressure
- Cough peak flow
- Nocturnal oxycapnography
- Arterial blood gas analysis
Regular respiratory follow-up, including nocturnal oxycapnography, is emphasized to detect early nocturnal hypoventilation and to guide timely escalation or initiation of ventilatory support.
The guideline also defines functional and gas-exchange thresholds to support clinical decision-making around starting noninvasive ventilation and, where required, escalation to invasive ventilatory support.
Initiating enzyme replacement therapy in LOPD
ERT remains the standard treatment for LOPD and is recommended for patients with objective evidence of muscle weakness or respiratory impairment. However, the guideline recognizes that clinical benefit from ERT may diminish over time in some patients.
Switching to alternative enzyme therapies is recommended for patients demonstrating lack of response or progressive deterioration. Newer enzyme therapies have demonstrated comparable safety and efficacy to standard ERT during the first year of treatment, though no head-to-head comparisons are available to support preferential selection. Therefore, the expert panel notes that no preferential first-line option can currently be recommended, and treatment response should be reviewed over time to inform switching decisions.
Multidisciplinary follow-up and long-term monitoring of LOPD
The guideline recommends regular follow-up by multidisciplinary teams experienced in managing LOPD. Symptomatic patients require close, frequent follow-up, while asymptomatic patients should be reviewed at least annually. Follow-up includes standardized evaluations of muscle strength, motor function, respiratory status, and patient-reported activity limitations to monitor disease progression and treatment effectiveness.
Reference
- Domínguez-González, 2026. Recommendations for the diagnosis, treatment, and follow-up of late-onset Pompe disease. https://www.doi.org/10.1016/j.nrleng.2025.501933
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