Molecular basis and clinical management of Pompe disease

• Main Authors: Giancarlo Parenti, Giuseppe Di Iorio, Simone Sampaolo, Giuseppe Fiorentino, Vincenzo Farina, Simona Fecarotta, Fabio Valente, Serena Ascione, Mario Caputi, Generoso Andria
• Format: Article
• Language: English
• Published: MDPI AG 2013-02-01
• Series: Cardiogenetics
• Subjects: Pompe disease, glycogen storage disease type II, acid a-glucosidase, acid maltase, metabolic myopathy.
• Online Access: http://www.pagepressjournals.org/index.php/cardiogen/article/view/905

Pompe disease (glycogenosis type II) is a rare autosomal recessive lysosomal storage disorder due to mutations of the <em>GAA</em> gene, leading to the deficiency of acid &alpha;-glucosidase and consequent glycogen storage in various tissues, mainly in the skeletal muscle, heart and liver. The consequent clinical picture is mainly due to the muscle and heart involvement, although clinical manifestations may be multi-systemic. The phenotype of patients is heterogeneous and the severity is inversely related to the residual enzymatic activity of acid &alpha;-glucosidase. More than 200 different mutations of <em>GAA</em> gene have been described and genotype/phenotype correlations have been established for some of them. Traditionally three forms have been described, <em>i.e. </em>early onset <em>classical</em> and <em>non-classical</em> forms and late onset attenuated forms. A severe hypertrophic cardiomyopathy in combination with conduction disorder in newborns represents a typical feature in the classic infantile presentation, while clinical picture in late onset forms is dominated by skeletal muscle dysfunction, resulting in mobility and respiratory problems. Enzyme replacement therapy with recombinant human GAA is the approved therapeutic approach in Pompe disease patients. Clinical trials on enzyme replacement therapy (ERT) support the efficacy in improving survival and hypertrophic cardiomyopathy, while efficacy seems to be variable on manifestations due to skeletal muscle involvement, mainly in lateonset patients. Considering the limitations of ERT and its high costs, innovative therapeutic approaches are now under development.