Question

…..Fabry Disease is a genetic defect in a lysosomal glycoconjugate processing (catabolizing) enzyme with serious clinical consequences (see, e.g.,

a) Expression of what nonreducing terminal monosaccharide residue would be most desirable in the N-linked oligosaccharides of a recombinant human lysosomal hydrolase designed to be used as a biotherapeutic for an inherited lysosomal storage disease (in this case, a recombinant α-galactosidase for the treatment of Fabry Disease)?

b)What is the advantage (i.e., what is the biological role) conferred by expression of the nonreducing terminal monosaccharide you identified above in a therapeutic designed to treat an inherited lysosomal storage disease?

Answer 1

a)Fabry disease is a condition of deficiency of alpha galactosidase enzyme. The patiennts with Fabry disease pocess a variant form of galactosidase i.e., Alpha-galactosidase B. The  α-N-acetylgalactosamine is the non reducing terminal monosaccharide residue can be used as biotherapeutic for an inherited lysosomal storage disease.It inhibits the alpha galactosidase B activity.