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.
N1 - Funding Information:
Dr. Bigger is a shareholder and SAB member of Orchard Therapeutics and Phoenix Nest and received honoraria and grant support from Orchard Therapeutics , BioMarin as well as several MPS charities including the UK Society for Mucopolysaccharide Diseases; Dr. Begley has received grant support and honoraria from Actelion, BioMarin Pharmaceutical Inc., Brains for Brain Onlus, Genzyme, GlaxoSmithKline, Hadley Hope Fund, Shire HGT, UK Engineering and Physical Science Research Council, UK Gauchers Association, UK Society for Mucopolysaccharide Diseases, Spanish Society for Mucopolysaccharide Diseases, Syngeneva, The Addi and Cassi Fund, and the European Union; Dr. Virgintino received funding from the Foundation Puglia 2015; Dr. Pshezhetsky received educational grants, travel grants, and honoraria from Genzyme/Sanofi, BioMarin, Alexion Pharma, Canadian Institutes of Health Research, JJB Foundation, and JLK Foundation.
Funding Information:
This work was supported by BioMarin Pharmaceutical Inc .
Funding Information:
The authors are grateful to Ismar Healthcare NV for their assistance in the writing of this manuscript, which was funded by BioMarin Pharmaceutical Inc. The expert meeting in Stockholm was also sponsored by BioMarin Pharmaceutical Inc.
Publisher Copyright:
© 2018 The Authors
PY - 2018/12
Y1 - 2018/12
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
UR - http://www.mendeley.com/research/anatomical-changes-pathophysiology-brain-mucopolysaccharidosis-disorders
U2 - 10.1016/j.ymgme.2018.08.003
DO - 10.1016/j.ymgme.2018.08.003
M3 - Article
SN - 1096-7192
VL - 125
SP - 322
EP - 331
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 4
ER -