title: Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment.
abstract: OBJECTIVE
  Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden.
  
  
  METHODS
  Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes. Sixty-seven patients had volumetric MRI. Subjects were grouped by age and phenotype and MRI and compared to 96 normal controls.
  
  
  RESULTS
  Prior to hematopoietic cell transplant, MPS IH patients were all cognitively average, but post-transplant, 59% were below average, but stable. Genotype and age at HCT were associated with cognitive ability. In attenuated MPS I, 40% were below average with genotype and somatic disease burden predicting their cognitive ability. White matter volumes were associated with IQ for controls, but not for MPS I. Gray matter volumes were positively associated with IQ in controls and attenuated MPS I patients, but negatively associated in MPS IH.
  
  
  CONCLUSIONS
  Cognitive impairment, a major difficulty for many MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association with white matter differed from controls. Many attenuated MPS patients have significant physical and/or cognitive problems and receive insufficient support services. Results provide direction for future clinical trials and better disease management.
authors.affiliation: University of Minnesota, United States. Electronic address: shapi004@umn.edu.
authors.forename: Elsa G
authors.initials: EG
authors.lastname: Shapiro
authors.affiliation: University of Minnesota, United States.
authors.forename: Igor
authors.initials: I
authors.lastname: Nestrasil
authors.affiliation: University of Minnesota, United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Rudser
authors.affiliation: University of Minnesota, United States.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Delaney
authors.affiliation: University of Minnesota, United States.
authors.forename: Victor
authors.initials: V
authors.lastname: Kovac
authors.affiliation: University of Minnesota, United States.
authors.forename: Alia
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: University of Minnesota, United States.
authors.forename: Brianna
authors.initials: B
authors.lastname: Yund
authors.affiliation: University of Minnesota, United States.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: University of Minnesota, United States.
authors.forename: Julie
authors.initials: J
authors.lastname: Eisengart
authors.affiliation: University of Minnesota, United States.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Niklason
authors.affiliation: Hospital for Sick Children, University of Toronto, Toronto, CA, United States.
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.affiliation: Hospital for Sick Children, Toronto, CA, United States.
authors.forename: Eva
authors.initials: E
authors.lastname: Mamak
authors.affiliation: UCSF Benioff Children's Hospital, University of California San Francisco, United States.
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Cowan
authors.affiliation: UCSF Benioff Children's Hospital, University of California San Francisco, United States.
authors.forename: Mara
authors.initials: M
authors.lastname: Bailey-Olson
authors.affiliation: UCSF Benioff Children's Hospital Oakland, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.affiliation: Emory University, United States.
authors.forename: Suma P
authors.initials: SP
authors.lastname: Shankar
authors.affiliation: Emory University, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cagle
authors.affiliation: Emory University, United States.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ali
authors.affiliation: Oregon Health & Science University, United States.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Steiner
authors.affiliation: University of Minnesota, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wozniak
authors.affiliation: University of Minnesota, United States.
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
authors.affiliation: University of Minnesota, United States.
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D003072:Cognition Disorders / Q000503:physiopathology / Q000628:therapy*; D056947:Enzyme Replacement Therapy; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D008059:Mucopolysaccharidosis I / Q000503:physiopathology / Q000628:therapy*; D063868:Patient Outcome Assessment; D066127:White Matter / Q000033:anatomy & histology / Q000473:pathology; D055815:Young Adult
keywords: Genotypes; Mucopolysaccharidosis Type I; Neurocognition; Neuroimaging