Topic: SGSH

Mucopolysaccharidosis type IIIA (MPS-IIIA) is a rare genetic metabolism disorder, belonging to the class of Lysosomal Storage Disorders (LSD). MPS-IIIA is caused by a mutation in the gene SGSH, leading to lysosomal enzyme sulfamidase deficiency and impaired degradation of heparan sulfate. Although the disease manifests during early childhood as an autistic spectrum disorder (ASD), the causes of ASD in MPS-IIIA are only poorly explored. Using a genetic mouse model of MPS-IIIA, we have recently discovered that these autistic-like behavioural symptoms (ALBs), which are known to be subtly regula

Mucopolysaccharidosis IIIA (MPS-IIIA) is a severe inborn error of metabolism caused by mutations in the sulfamidase gene (SGSH), which encodes a lysosomal enzyme involved in the metabolism of heparan sulfate (HS). Defective sulfamidase activity leads to the accumulation of HS within lysosomes, resulting in lysosomal dysfunction and ultimately leading to neurodegeneration and dementia in affected children. However, preceding dementia, individuals often exhibit severe and debilitating autistic-like behaviors, including self-injury, stereotypic behaviors, and social impairment. These autistic sym

Since the first enzyme replacement therapy (ERT) for Gaucher disease was approved in 1991, ERT has become standard of care for several lysosomal storage diseases (LSD), collectively characterized by dysfunctional lysosomal enzymes leading to pathological substrate accumulation. Sanfilippo Syndrome type A (MPSIIIA) is a monogenetic disease caused by >150 different loss-of-function mutations in the lysosomal enzyme N-Sulfoglucosamine Sulfohydrolase (SGSH), resulting in accumulation of heparan sulfate (HS). This accumulation disrupts cellular homeostasis with consequences for autophagy and mit