Nocturnal sleep abnormalities occur before motor function deterioration in early-treated patients with infantile-onset Pompe disease: a two-decade newborn screening cohort study.

Early institutions of enzyme replacement therapy (ERT) for infantile-onset Pompe disease (IOPD) greatly improved patients' outcome. However, the long-term prognosis of patients' muscular and respiratory systems has not been fully elucidated. We conducted a longitudinal study for a cohort of early-treated IOPD patients with continuous monitoring of motor and respiratory functions (spirometry and polysomnography). Statistical analyses were performed for the relationship between Gross Motor Function Measure (GMFM), forced vital capacity (FVC), apnea-hypopnea index (AHI), and oxygen desaturation index (ODI). Sixteen patients (13 classical and 3 nonclassical IOPD) were followed up to a median age of 16.0 years (range 7.5-19.6), providing approximately 244 patient-years of observation and 132 polysomnographic assessments. Eleven of the 16 patients developed an AHI greater than 5 events/hour (indicating moderate obstructive sleep apnea, with nearly all events being obstructive apneas or hypopneas) at a Kaplan-Meier-estimated median age of 7.8 years. Night-time respiratory support was prescribed for 7 patients at a median age of 17.5 years. Data analyses revealed that FVC and AHI deteriorated faster in patients who became non-ambulatory than in other patients with better motor outcome. However, although FVC and AHI correlated slightly (r = -0.48), cases with sleep apnea were observed in patients with relatively normal gross motor or FVC. Nocturnal sleep abnormalities can occur in early-treated IOPD patients before frank deterioration of motor and respiratory function. Polysomnography is recommended for all those patients, and night-time respiratory support may be necessary to prevent morbidity and mortality.