title: Cognitive, medical, and neuroimaging characteristics of attenuated mucopolysaccharidosis type II.
abstract: The phenotype of attenuated mucopolysaccharidosis type II (MPS II), also called Hunter syndrome, has not been previously studied in systematic manner. In contrast to the "severe" phenotype, the "attenuated" phenotype does not present with behavioral or cognitive impairment; however, the presence of mild behavior and cognitive impairment that might impact long-term functional outcomes is unknown. Previously, significant MRI abnormalities have been found in MPS II. Recent evidence suggests white matter abnormalities in many MPS disorders.
  
  
  METHODS
  As the initial cross-sectional analysis of a longitudinal study, we studied the association of brain volumes and somatic disease burden with neuropsychological outcomes, including measures of intelligence, memory, and attention in 20 patients with attenuated MPS II with a mean age of 15.8. MRI volumes were compared to 55 normal controls.
  
  
  RESULTS
  While IQ and memory were average, measures of attention were one standard deviation below the average range. Corpus callosum volumes were significantly different from age-matched controls, differing by 22%. Normal age-related volume increases in white matter were not seen in MPS II patients as they were in controls. Somatic disease burden and white matter and corpus callosum volumes were significantly associated with attention deficits. Neither age at evaluation nor age at starting treatment predicted attention outcomes.
  
  
  CONCLUSIONS
  Despite average intelligence, attention is compromised in attenuated MPS II. Results confirm an important role of corpus callosum and cortical white matter abnormality in MPS II as well as the somatic disease burden in contributing to attention difficulties. Awareness by the patient and caregivers with appropriate management and symptomatic support will benefit the attenuated MPS II patient.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Brianna
authors.initials: B
authors.lastname: Yund
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Rudser
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Alia
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Kovac
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Nestrasil
authors.affiliation: Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.affiliation: Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Eva
authors.initials: E
authors.lastname: Mamak
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.affiliation: Department of Pediatrics, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Steiner
authors.affiliation: Department of Neurology, New York University, New York, NY, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Lau
authors.affiliation: Department of Child and Adolescent Psychiatry, New York University, New York, NY, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Vekaria
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Wozniak
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Kelvin O
authors.initials: KO
authors.lastname: Lim
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Delaney
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Chester
authors.initials: C
authors.lastname: Whitley
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: shapi004@umn.edu.
authors.forename: Elsa G
authors.initials: EG
authors.lastname: Shapiro
mesh_terms: D000293:Adolescent; D000328:Adult; D001288:Attention; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D003337:Corpus Callosum / Q000473:pathology; D003430:Cross-Sectional Studies; D056947:Enzyme Replacement Therapy; D005260:Female; D006801:Humans; D007360:Intelligence; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D016532:Mucopolysaccharidosis II / Q000473:pathology* / Q000503:physiopathology* / Q000523:psychology; D059906:Neuroimaging; D010641:Phenotype; D066127:White Matter / Q000473:pathology; D055815:Young Adult
keywords: Attenuated; MRI brain volumes; Mucopolysaccharidosis type II; Neuropsychological outcomes