The AGA gene provides instructions for producing an enzyme called aspartylglucosaminidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Within lysosomes, the enzyme helps break down complexes of sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins). Specifically, this enzyme cuts glycoproteins between a protein building block (amino acid) called asparagine and a sugar molecule called N-acetylglucosamine. This cut is one of the last steps in breaking down a glycoprotein in the lysosome.
More than 30 mutations in the AGA gene have been found to cause aspartylglucosaminuria. Most of these mutations change one amino acid in aspartylglucosaminidase. One mutation found in 98 percent of people with this condition in Finland replaces the amino acid cysteine with the amino acid serine at position 163 in the enzyme (written as Cys163Ser or C163S). Many mutations, including C163S, disrupt the proper folding of aspartylglucosaminidase, resulting in an enzyme that cannot effectively break down glycoproteins. A buildup of glycoproteins seems to particularly affect nerve cells in the brain; loss of these cells causes a progressive decline in mental functioning and the other signs and symptoms of aspartylglucosaminuria.
- N4-(N-acetyl-beta-glucosaminyl)-L-asparagine amidase