2-25.3 produces an inactive 110 kD precursor which is transported to the lysosomal compartment and processed into the 95 kD intermediate and the fully active forms of 76 and 70 kD (1, 10). More than 200 mutations in the GAA gene have been described up to date (http://www2.eur.nl/fgg/ch1/pompe)

(8-10). GSD II (Pompe disease) is inherited as an autosomal recessive trait. The most common inheritance scenario which results in Pompe disease is when both parents Inhibitors,research,lifescience,medical are carriers, usually asymptomatic. In this case, in each pregnancy the chances are: 1 in 4 (25%) that the child will receive two defective genes and thus inherit the disease 2 in 4 (50%) that the child will inherit only one defective gene and become a carrier 1 in 4 (25%) that the child will be completely unaffected (Fig. 1). Figure 1. Characteristics of an autosomal recessive inheritance. Far less common inheritance scenarios include: Inhibitors,research,lifescience,medical If both parents have Pompe disease, then every child will inherit the disease If one parent has the disease and the other is a carrier, each child has a 50% chance of inheriting the disease and a 50% chance of being a carrier Historically, children with classic infantile Pompe disease do not

survive enough to reproduce, Inhibitors,research,lifescience,medical although the availability of therapy may alter this expectation through improved fitness of those individuals Inhibitors,research,lifescience,medical who respond to enzyme replacement therapy. In contrast, many individuals with later-onset disease survive into their 50′s and 60′s. The offspring of an individual with a later-onset

form of GSD II are obligate carriers for a disease-causing mutation in GAA. Furthermore, each sib of an obligate heterozygote is at a 50% risk of being a carrier (11-14). Carrier detection In families in which Inhibitors,research,lifescience,medical a diagnosis of Pompe disease has been made, there is a risk that relatives may also have the disease or be carriers. Therefore it is important to test siblings of an affected child. Carrier detection can be achieved by two main genetic approach: biochemical testing, and molecular testing (7, 15, 16). Biochemical testing Measurement of acid alpha-glucosidase enzyme activity Fossariinae in skin fibroblasts, muscle, or peripheral blood leukocytes is unreliable for carrier determination because of significant overlap in http://www.selleckchem.com/products/AZD6244.html residual enzyme activity levels between obligate carriers and the general (non-carrier) population. Molecular testing Mutation analysis is the only way to identify carriers, who do not have the disease, but “carry” the gene defect and may pass it on to their own children (15, 16). Genetic counseling Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.