Management of presymptomatic juvenile patients with late-onset Pompe disease (LOPD)

Late-onset Pompe disease (LOPD) includes patients from 1 year of age to adulthood. The vast heterogeneity in clinical manifestations and disease progression is not fully explained; however, a short disease duration and a young age seem to be good predictors of a better response to treatment. For this purpose, we investigated and followed up a cohort of 13 juvenile patients with LOPD from the clinical and therapeutic point of view, mainly pointing out the transition from presymptomatic to symptomatic status. We retrospectively collected clinical, morphological, biochemical and molecular data from 13 juvenile LOPD patients. Motor and respiratory functional data, obtained during annual follow-up visits, were analyzed. The data included serial evaluations of the Medical Research Council (MRC) scale, the 6-Minute Walking Test (6MWT), the Gait, Stairs, Gower, and Chair (GSGC) score, and seated and supine Forced Vital Capacity (FVC). Muscle Magnetic Resonance Imaging (MRI) was also included, although it was not performed in all cases. Currently, patients mean age is 18 years. All patients but one were diagnosed because of an isolated hyperCKemia: the mean age at diagnosis was 6.8 years (range 1-18). The onset of symptoms occurred from 6 months to 12 years after the diagnosis. The mean clinical follow-up duration was 9 years (range 2-18). From the genetic point of view, the most shared mutation was c.32-13T>G, found in twelve patients as compound heterozygosis. Seven patients underwent muscle biopsy, which showed vacuolar myopathy with glycogen accumulation in four of them with unspecific changes in the other three cases. Five patients developed proximal muscle weakness during the follow-up with a mild waddling gait and a positive Gowers manoeuver. Muscle MRI revealed mild hypotrophy of the thighs at the development of symptoms in four out of five cases. Four patients started alglucosidase alfa, and one avalglucosidase alfa. These five patients on Enzyme Replacement Therapy (ERT) showed motor and respiratory stability in the following years. Timely identification of emerging clinical manifestations in presymptomatic LOPD patients, as a result of careful follow-up, is essential to start prompt treatment to modify the disease natural course.