Mucolipidosis type II α/β with a homozygous missense mutation in the GNPTAB gene

摘要

The uridine diphosphate (UDP)-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (termed GlcNAc-1-phosphotransferase; EC 2.7.8.17) is a Golgi-resident 540-kDa hexameric transmembrane enzyme composed by three subunits, (X2P2Y2! which catalyzes the first step in the formation of the M6P recognition marker on lysosomal enzymes. This marker is essential for the proper recognition of newly synthesized lysosomal hydrolases by specific M6P receptors, required for lysosomal targeting. The receptor-enzyme complexes are selectively transported and, upon arrival in the endosomal/lysosomal compartment, dissociate due to the typical low pH. Lysosomal proteins are then delivered to the lysosomes, while the M6P receptors return to the Golgi apparatus for subsequent rounds of [Braulke and Bonifacino, 2009] transport. Impairments in the formation of the M6P recognition marker due to defective GlcNAc-1 -phosphotransferase are the basis of two rare lysosomal storage disorders: Mucolipidosis II (ML II) and Mucolipidosis III (ML III).