Clinical and therapeutic clues from a long-term follow-up: a single center experience on a large LOPD population.

Abstract

Pompe disease is an inherited metabolic disorder, caused by acid alpha-glucosidase (GAA) enzyme deficiency. Late-onset form (LOPD) usually presents with proximal and axial myopathy, followed by progressive respiratory involvement. Since 2006, enzyme replacement therapy (ERT) has been the gold standard treatment. Recently, two ERTs of second generation have been approved. Several studies have demonstrated the benefits of the first generation ERT (FG-ERT), although outcomes are quite variable, and very long-term data are limited. In fact, functional long-term studies are still needed to clearly point out the prolonged efficacy of FG-ERT. We describe a cohort of 49 LOPD patients, providing a very long-term follow-up of motor and pulmonary function of 30 of them treated by FG-ERT (from 2 to 20 years), using 6MWT, FVC, and GSGC score to evaluate patients' responses. 6MWT remained quite stable in the first 4 years of therapy, followed by a slow decline of its value of about 21%. FVC showed an improving trend in the first 4 years, followed by a decline of about 12%. Along the follow-up, GSGC score worsened with an increasing of about 30% of the total score values. Although long-term results evidenced variable therapeutic responses, the general trend is an improvement in motor and respiratory functions during the first 2-4 years of treatment, followed by a variable degree of decline. According to these results, and in line with recent EPOC recommendations, it is strongly suggested to start therapy in symptomatic patients, but also to carefully manage presymptomatic patients to timely supply ERT treatment.