title: The natural course of gross motor deterioration in metachromatic leukodystrophy.
abstract: OBJECTIVE
  Motor deterioration is a key feature in metachromatic leukodystrophy (MLD). The lack of data about its natural course impedes evaluation of therapeutic interventions. This study aimed to provide data about motor decline in MLD.
  
  
  METHODS
  Fifty-nine patients (27 males, 32 females) with MLD (21 with late-infantile MLD and 38 with juvenile MLD) were recruited within a nationwide survey (the German LEUKONET). Median (range) age at onset was 17 months (9-27) for the group with late-infantile MLD and 6 years 2 months (2y 11mo-14y) for the group with juvenile MLD. Gross motor function was assessed using the Gross Motor Function Classification for MLD.
  
  
  RESULTS
  In late-infantile MLD, all patients showed loss of all gross motor function until 3 years 4 months of age. Patients with juvenile MLD showed a more variable and significantly longer motor decline (p<0.001). For a patient with the juvenile form showing first gait disturbances, the probability of remaining stable for more than 1 year was 84%, and 51% for more than 2 years. Having lost independent walking, subsequent motor decline was as steep as in the late-infantile form (median 5 mo, interquartile range 3-22).
  
  
  CONCLUSIONS
  The course of motor disease was more variable in juvenile MLD with respect to onset and dynamics. However, the motor decline after the loss of independent walking was similarly steep in both forms. These data can serve as a reference for clinical studies that are topics of current research and allow definition of inclusion/exclusion criteria.
authors.affiliation:  Department of Paediatric Neurology and Developmental Medicine, University Children's Hospital Tübingen, Tübingen. Department of Medical Biometry, University of Tübingen, Tübingen. Department of Physiology, University of Bonn, Bonn, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kehrer
authors.affiliation:  Department of Paediatric Neurology and Developmental Medicine, University Children's Hospital Tübingen, Tübingen. Department of Medical Biometry, University of Tübingen, Tübingen. Department of Physiology, University of Bonn, Bonn, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Blumenstock
authors.affiliation:  Department of Paediatric Neurology and Developmental Medicine, University Children's Hospital Tübingen, Tübingen. Department of Medical Biometry, University of Tübingen, Tübingen. Department of Physiology, University of Bonn, Bonn, Germany.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gieselmann
authors.affiliation:  Department of Paediatric Neurology and Developmental Medicine, University Children's Hospital Tübingen, Tübingen. Department of Medical Biometry, University of Tübingen, Tübingen. Department of Physiology, University of Bonn, Bonn, Germany.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Krägeloh-Mann
authors.affiliation:  Department of Paediatric Neurology and Developmental Medicine, University Children's Hospital Tübingen, Tübingen. Department of Medical Biometry, University of Tübingen, Tübingen. Department of Physiology, University of Bonn, Bonn, Germany.
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001192:Arylsulfatases / Q000172:deficiency; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D006306:Health Surveys; D006801:Humans; D053208:Kaplan-Meier Estimate; D007966:Leukodystrophy, Metachromatic / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D008297:Male; D009069:Movement Disorders / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D001192:Arylsulfatases