title: Long-term cognitive follow-up in children treated for Maroteaux-Lamy syndrome.
abstract: BACKGROUND
  It remains unclear to what extent the brain is affected by Maroteaux-Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood-brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT.
  
  
  METHODS
  In a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning and brain magnetic resonance imaging prospectively at the start of ERT and at regular times thereafter up to 4.8 years. We also assessed the children's clinical characteristics, their siblings' cognitive development, and their parents' educational levels.
  
  
  RESULTS
  The patients' intelligence scores ranged from normal to mentally delayed (range test scores 52-131). In 90%, their scores remained fairly stable during follow-up, generally lying in the same range as their siblings' test scores (median for patients = 104, median for siblings = 88) and comparing well with the parental educational levels. Native-speaking patients had higher intelligence test scores than non-native-speaking patients. Two patients, both with high baseline glycosaminoglycan levels in their urine and severe mutations in the arylsulfatase B gene, scored clearly lower than expected. Patients with pY210C performed best. Brain abnormalities were aspecific, occurring more in patients with severe symptoms.
  
  
  CONCLUSIONS
  Our study shows that cognitive development in MPS VI patients is determined not only by familial and social-background factors, but, in patients with a severe form of the disease, also by the disease itself. Therefore in patients with severe disease presentation cognition should be monitored carefully.
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center - Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Berendine J
authors.initials: BJ
authors.lastname: Ebbink
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center - Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Marion M G
authors.initials: MM
authors.lastname: Brands
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center - Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.|Department of Pediatric Neurology, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Johanna M P
authors.initials: JM
authors.lastname: van den Hout
authors.affiliation: Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Lequin
authors.affiliation: Department of Pediatrics, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Robert R J
authors.initials: RR
authors.lastname: Coebergh van den Braak
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center - Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Rianne L
authors.initials: RL
authors.lastname: van de Weitgraven
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center - Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands.
authors.forename: Iris
authors.initials: I
authors.lastname: Plug
authors.affiliation: Department of Pediatric Neurology, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Femke K
authors.initials: FK
authors.lastname: Aarsen
authors.affiliation: Center for Lysosomal and Metabolic Diseases, Department of Pediatrics, Erasmus MC University Medical Center - Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nl.
authors.forename: Ans T
authors.initials: AT
authors.lastname: van der Ploeg
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology*; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007223:Infant; D007360:Intelligence / Q000502:physiology; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology* / Q000652:urine; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics
chemical_list: D006025:Glycosaminoglycans; D020051:N-Acetylgalactosamine-4-Sulfatase