title: A Prospective Natural History Study of Mucopolysaccharidosis Type IIIA.
abstract: OBJECTIVE
  To characterize the clinical course of mucopolysaccharidosis type IIIA (MPS IIIA), and identify potential endpoints for future treatment trials.
  
  
  METHODS
  Children with a confirmed diagnosis of MPS IIIA, functioning above a developmental age of 1 year, were followed for up to 2 years. Cognitive status and brain atrophy were assessed by standardized tests and volumetric magnetic resonance imaging, respectively. Liver and spleen volumes and cerebrospinal fluid and urine biomarker levels were measured.
  
  
  RESULTS
  Twenty-five children, from 1.1 to 18.4 years old, were enrolled, and 24 followed for at least 12 months. 19 exhibited a rapidly progressing (RP) form of MPS IIIA, and 5, a more slowly progressing form. Children with RP plateaued in development by 30 months, followed by rapid regression after 40-50 months. In patients with RP, cognitive developmental quotients showed consistent steep declines associated with progressive cortical gray matter atrophy. Children with slowly progressing had a similar but more prolonged course. Liver and spleen volumes were approximately double normal size, and cerebrospinal fluid and urine heparin sulfate levels were elevated and relatively constant over time.
  
  
  CONCLUSIONS
  Developmental quotient and cortical gray matter volume are sensitive markers of disease progression in MPS IIIA, and may have utility as clinical endpoints in treatment trials. For optimal outcomes, treatment may need to be instituted in children before the onset of steep cognitive decline and brain atrophy.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01047306.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN. Electronic address: shapi004@umn.edu.
authors.forename: Elsa G
authors.initials: EG
authors.lastname: Shapiro
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN.
authors.forename: Igor
authors.initials: I
authors.lastname: Nestrasil
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Delaney
authors.affiliation: Division of Biostatistics, University of Minnesota, Minneapolis, MN.
authors.forename: Kyle
authors.initials: K
authors.lastname: Rudser
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN.
authors.forename: Victor
authors.initials: V
authors.lastname: Kovac
authors.affiliation: Shire, Lexington, MA.
authors.forename: Nitin
authors.initials: N
authors.lastname: Nair
authors.affiliation: Shire, Lexington, MA.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Richard
authors.affiliation: Shire, Lexington, MA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Haslett
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, MN.
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
mesh_terms: D000293:Adolescent; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000652:urine; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D003071:Cognition; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D007223:Infant; D008099:Liver / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009084:Mucopolysaccharidosis III / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000523:psychology / Q000652:urine; D009929:Organ Size; D011446:Prospective Studies; D012720:Severity of Illness Index; D013154:Spleen / Q000473:pathology
chemical_list: D015415:Biomarkers