Abstract
Pompe disease (glycogenosis type II) is a rare autosomal recessive lysosomal storage disorder due to mutations of the GAA gene, leading to the deficiency of acid α-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 α-glucosidase. More than 200 different mutations of GAA gene have been described and genotype/phenotype correlations have been established for some of them. Traditionally three forms have been described, i.e. early onset classical and non-classical 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.
Highlights
Affected skeletal muscles are the respiratory hypertrophic cardiomyopathy, while efficacy PD has been untreatable until 2006 when and proximal muscles of the limbs, patients seems to be variable on manifestations due to enzyme replacement therapy (ERT) with usually show severe respiratory problems, skeletal muscle involvement, mainly in late- recombinant human GAA has been characterized by recurrent respiratory infec
When the vital capacon a male who developed cardiomyopathy at 12 costals muscles, typical of Pompe disease. ity falls below 55% of predicted normal values, years of age and died of heart failure at age 15 Patients should always be asked if they suffer the onset of insidiously progressive hypercapyears without any clinical and/or histological from orthopnea, exertional dyspnea and inef- nia is likely.[38]
The marketing approval of NB-DNJ for treatment of Gaucher and Niemann-Pick type C diseases represents an advantage for its clinical use in PD, the feasibility of this approach appears limited, considering that only a small percentage of PD patients with responsive mutations could benefit from this therapy
Summary
Second University of Naples, Italy e on Abstract us Pompe disease (glycogenosis type II) is a l rare autosomal recessive lysosomal storage ia disorder due to mutations of the GAA gene, leading to the deficiency of acid a-glucosidase c and consequent glycogen storage in various r tissues, mainly in the skeletal muscle, heart e and liver. More than 200 different mutations of GAA gene n have been described and genotype/phenotype o correlations have been established for some of N them. The disease is characterized by broad phenotypic heterogeneity and varying levels of residual enzyme activity, which are inversely related to the severity of clinical manifestations. Distinct phenotypes have been described, based on age at onset, organ involvement, severity, and rate of progression (Table 1).
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