Cognitive outcome of patients with classic infantile Pompe disease receiving enzyme therapy.

OBJECTIVE: Classic infantile Pompe disease affects many tissues, including the brain. Untreated infants die within their first year. Although enzyme-replacement therapy (ERT) significantly increases survival, its potential limitation is that the drug cannot cross the blood-brain barrier. We therefore investigated long-term cognitive development in patients treated with ERT. METHODS: We prospectively assessed cognitive functioning in 10 children with classic infantile Pompe disease who had been treated with ERT since 1999. Brain imaging was performed in 6 children. RESULTS: During the first 4 years of life, developmental scores in 10 children ranged from above-average development to severe developmental delay; they were influenced by the type of intelligence test used, severity of motor problems, speech/language difficulties, and age at start of therapy. Five of the children were also tested from 5 years onward. Among them were 2 tetraplegic children whose earlier scores had indicated severe developmental delay. These scores now ranged between normal and mild developmental delay and indicated that at young age poor motor functioning may interfere with proper assessment of cognition. We found delayed processing speed in 2 children. Brain imaging revealed periventricular white matter abnormalities in 4 children. CONCLUSIONS: Cognitive development at school age ranged between normal and mildly delayed in our long-term survivors with classic infantile Pompe disease treated with ERT. The oldest was 12 years. We found that cognition is easily underestimated in children younger than 5 years with poor motor functioning.

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

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.