Schindler disease type 1

Schindler disease type 1 is caused by mutations in the NAGA gene. This gene provides instructions for making the enzyme alpha-N-acetylgalactosaminidase.This enzyme works in the lysosomes  (compartments within cells that digest and recycle materials) to help break down complexes called glycoproteins and glycolipids (sugar molecules attached to certain proteins and fats). More specifically, alpha-N-acetylgalactosaminidase helps remove a molecule called alpha-N-acetylgalactosamine from sugars in these complexes.^[1]

Mutations in the NAGA gene interfere with the ability of the alpha-N-acetylgalactosaminidase enzyme to perform its role in breaking down glycoproteins and glycoliipids. These substances accumulate in the lysosomes and cause cells to malfunction and eventually die. Cell damage in the nervous system and other tissues and organs of the body leads to the signs and symptoms of Schindler disease type 1.^[1]   

The NAGA gene is located on the long (q) arm of chromosome 22 at position 13.2.^[2][3]

Schindler disease type 1 is caused by a homozygous NAGA gene (22q13.2) mutation resulting in a Glu325-to-Lys (E325K) (amino acid) substitution.^[2][3] These mutations are believed to change the three dimensional shape of the alpha-N-acetylgalactosaminidase enzyme, leading to its dysfunction, instability, and rapid degradation.^[2]