![]() Patients with the classic infantile onset form, the most severe and rapidly progressive phenotype, die within the first year of life from cardiorespiratory insufficiency if untreated ( 3, 4). This genetic defect leads to the deficient activity of GAA resulting in impaired glycogen degradation and accumulation within the lysosomes ( 1).Ĭlinically, PD encompasses a highly variable range of phenotypes that differ in the age of onset, extent of organ involvement, and rate of progression ( 2). Pompe disease (PD-MIM# 232300), is an autosomal recessive lysosomal storage disorder due to mutations in the acid alpha-glucosidase ( GAA) gene (MIM#606800) encoding the lysosomal GAA. The information collected in this review provides an overview of the molecular genetics of PD and can be used to facilitate diagnosis and genetic counseling of families affected by this disorder. In addition, whenever possible, we discuss the phenotype/genotype correlation. ![]() In this article, we review the spectrum of GAA mutations, their distribution in different populations, and their classification according to their impact on GAA splicing process, protein expression and activity. However, an exception is represented by the c.-32-13T>G splice mutation that is very common in patients of Caucasian origin affected by the childhood/adult form of the disease, with an allelic frequency ranging from 40% to 70%. Most GAA mutations are private or found in a small number of families. All types of mutations have been described missense variants are the most frequent type followed by small deletions. The GAA gene has been localized to chromosome 17q25.2-q25.3 and to date, 582 mutations distributed throughout the whole gene have been reported (HGMD: ). Clinically, the disease has been classically classified in infantile and childhood/adult forms. The enzymatic deficiency leads to the accumulation of glycogen within the lysosomes. Pompe disease (PD) is an autosomal recessive lysosomal disorder caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme due to mutations in the GAA gene.
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