Facial‐muscle weakness, speech disorders and dysphagia are common in patients with classic infantile Pompe disease treated with enzyme therapy

Abstract

Classic infantile Pompe disease is an inherited generalized glycogen storage disorder caused by deficiency of lysosomal acid α-glucosidase. If left untreated, patients die before one year of age. Although enzyme-replacement therapy (ERT) has significantly prolonged lifespan, it has also revealed new aspects of the disease. For up to 11 years, we investigated the frequency and consequences of facial-muscle weakness, speech disorders and dysphagia in long-term survivors. Sequential photographs were used to determine the timing and severity of facial-muscle weakness. Using standardized articulation tests and fibreoptic endoscopic evaluation of swallowing, we investigated speech and swallowing function in a subset of patients. This study included 11 patients with classic infantile Pompe disease. Median age at the start of ERT was 2.4 months (range 0.1-8.3 months), and median age at the end of the study was 4.3 years (range 7.7 months −12.2 years). All patients developed facial-muscle weakness before the age of 15 months. Speech was studied in four patients. Articulation was disordered, with hypernasal resonance and reduced speech intelligibility in all four. Swallowing function was studied in six patients, the most important findings being ineffective swallowing with residues of food (5/6), penetration or aspiration (3/6), and reduced pharyngeal and/or laryngeal sensibility (2/6). We conclude that facial-muscle weakness, speech disorders and dysphagia are common in long-term survivors receiving ERT for classic infantile Pompe disease. To improve speech and reduce the risk for aspiration, early treatment by a speech therapist and regular swallowing assessments are recommended.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-011-9404-7) contains supplementary material, which is available to authorized users.

Phase I/II Trial of Adeno-Associated Virus–Mediated Alpha-Glucosidase Gene Therapy to the Diaphragm for Chronic Respiratory Failure in Pompe Disease: Initial Safety and Ventilatory Outcomes

“…Although ERT has become the standard of care for Pompe disease, the clinical benefits of ERT have been confounded by immune responses (Kishnani et al, 2007) and progression of neuromuscular impairments (Nicolino et al, 2009;Chakrapani et al, 2010;van Gelder et al, 2012). In particular, longer-term evaluations reveal progressive respiratory insufficiency and a requirement for invasive ventilation in many surviving subjects, despite the chronic use of ERT (Nicolino et al, 2009;Chakrapani et al, 2010).…”

Lower Urinary Tract Symptoms and Incontinence in Children with Pompe Disease

“…Retrospective reviews have shown improvement in cardiac and lung function and gross motor function in long-term survivors . Persistent deficiencies in hearing loss, risk of arrhythmias, dysphagia, osteopenia, fecal incontinence, and other longterm complications have been addressed (Jones et al 2010;van Gelder et al 2012;Tan et al 2013). However, we are unaware of any published data on LUTS and urinary incontinence in children with PD.…”

“…Urinary incontinence is an often undertreated condition that can greatly affect quality of life (Jones et al 2010;van Gelder et al 2012;Tan et al 2013;Thibodeau et al 2013). Ninety percent of children achieve daytime urinary continence by the age of 5 (Hunskaar et al 2003).…”

Molecular Basis and Clinical Management of Pompe Disease

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