Mucopolysaccharidosis type III Novel insights and challenges

Mucopolysaccharidosis type III, also known as MPS III or Sanfilippo syndrome, is a lysosomal storage disorder with an autosomal recessive (AR) inheritance pattern. MPS III is part of the mucopolysaccharidoses (MPSs), a group of seven different genetic disorders, all accumulating different types of glycosaminoglycans (GAGs). MPS III is caused by an enzyme deficiency of one of the four lysosomal enzymes involved in the degradation of the GAG heparan sulfate (HS). The four enzymes correspond with the four different subtypes: MPS IIIA (heparan N-sulfatase; SGSH), MPS IIIB (N-α-acetylglucosaminidase; NAGLU), MPS IIIC (acetyl CoA:α-glucosaminide N-acetyltransferase; HGSNAT), and MPS IIID (N-acetylglucosamine 6-sulfatase; GNS). Clinically, these subtypes are indistinguishable.
This thesis comprises a number of studies aiming to improve knowledge about the MPS III disease course and the phenotypic spectrum, to provide insights in the attitudes towards preconception expanded carrier screening and the psychosocial well-being of parents of MPS III patients, and finally, to provide an overview of possible future therapies, highlighting the challenges.