TY - JOUR
T1 - Anatomical changes and pathophysiology of the brain in mucopolysaccharidosis disorders
AU - Bigger, Brian W.
AU - Begley, David J.
AU - Virgintino, Daniela
AU - Pshezhetsky, Alexey V.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Mucopolysaccharidosis (MPS) disorders are caused by deficiencies in lysosomal enzymes, leading to impaired glycosaminoglycan (GAG) degradation. The resulting GAG accumulation in cells and connective tissues ultimately results in widespread tissue and organ dysfunction. The seven MPS types currently described are heterogeneous and progressive disorders, with somatic and neurological manifestations depending on the type of accumulating GAG. Heparan sulfate (HS) is one of the GAGs stored in patients with MPS I, II, and VII and the main GAG stored in patients with MPS III. These disorders are associated with significant central nervous system (CNS) abnormalities that can manifest as impaired cognition, hyperactive and/or aggressive behavior, epilepsy, hydrocephalus, and sleeping problems. This review discusses the anatomical and pathophysiological CNS changes accompanying HS accumulation as well as the mechanisms believed to cause CNS abnormalities in MPS patients. The content of this review is based on presentations and discussions on these topics during a meeting on the brain in MPS attended by an international group of MPS experts.
AB - Mucopolysaccharidosis (MPS) disorders are caused by deficiencies in lysosomal enzymes, leading to impaired glycosaminoglycan (GAG) degradation. The resulting GAG accumulation in cells and connective tissues ultimately results in widespread tissue and organ dysfunction. The seven MPS types currently described are heterogeneous and progressive disorders, with somatic and neurological manifestations depending on the type of accumulating GAG. Heparan sulfate (HS) is one of the GAGs stored in patients with MPS I, II, and VII and the main GAG stored in patients with MPS III. These disorders are associated with significant central nervous system (CNS) abnormalities that can manifest as impaired cognition, hyperactive and/or aggressive behavior, epilepsy, hydrocephalus, and sleeping problems. This review discusses the anatomical and pathophysiological CNS changes accompanying HS accumulation as well as the mechanisms believed to cause CNS abnormalities in MPS patients. The content of this review is based on presentations and discussions on these topics during a meeting on the brain in MPS attended by an international group of MPS experts.
KW - Gangliosides
KW - Heparan sulfate proteoglycans
KW - Mucopolysaccharidosis
KW - Neuropathology
UR - http://www.scopus.com/inward/record.url?scp=85052082216&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2018.08.003
DO - 10.1016/j.ymgme.2018.08.003
M3 - Article
AN - SCOPUS:85052082216
SN - 1096-7192
JO - MOLECULAR GENETICS AND METABOLISM
JF - MOLECULAR GENETICS AND METABOLISM
ER -
