Pompe disease – a progressive multisystemic disorder: diagnostic and treatment challenges

Pompe disease is a progressive multisystemic disease caused by defi ciency of lysosomal enzyme acid alfa glucosidase, which leads to impaired lysosomal glycogen breakdown, subsequent glycogen accumulation, and cascade of pathological processes. Pompe disease presents as a continuous spectrum of phenotypes, from infantile onset to less severe late-onset type. Infantile-onset Pompe disease is characterized by progressive hypertrophic cardiomyopathy with fatal course within the fi rst year of life, if untreated. Enzyme replacement therapy has dramatically changed the natural course of the disease and resulted in much longer survival. In children with infantile-onset disease, who survived thanks to the treatment, a new phenotype is emerging. Late-onset Pompe disease can present with variable signs, and although muscle weakness and respiratory involvement are dominant features, it is a multisystemic disease. The characteristic triad of clinical manifestation is limb-girdle, paraspinal and respiratory muscle weakness, which is usually present in later stages of the disease. However, in earlier stages, only some of the characteristic signs, or other unspecifi c signs may be present. Therefore, recognition of the disease and treatment are often delayed. A simple diagnostic method is dried blood spot enzyme activity assay. Analysis should be performed in the patients with positive family history, high serum creatine kinase of unclarifi ed aetiology, including asymptomatic ones, and/or with other signs and symptoms of Pompe disease. Long term follow-up of patients with late-onset form treated with enzyme replacement therapy has shown that treatment lowers mortality rate, stabilizes respiratory function and slows down progression of the disease. Modifi cations of enzyme replacement treatment and novel therapeutic approaches are being developed to overcome the perceived limitations of currently available therapy.
Keywords: RARE DISEASES; CHILDREN
Category: Review
Volume: Vol. 64, No 4, october - december 2020
Authors: Danijela Petković Ramadža
Reference work: Paediatr Croat. 2020;64:253-9
DOI: http://dx.doi.org/10.13112/PC.2020.37

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