title: Natural history of alpha mannosidosis a longitudinal study.
abstract: BACKGROUND
  Alpha-Mannosidosis is a rare lysosomal storage disorder, caused by the deficiency of the enzyme alpha-Mannosidase. Clinically it is characterized by hearing impairment, skeletal and neurological abnormalities and mental retardation. In order to characterize the clinical features and disease progression of patients affected by alpha-Mannosidosis, a survey study was conducted. 43 patients from 4 European countries participated in this longitudinal study. Age range of the participants was 3 to 42 years. For each patient a medical history, complete physical and neurological examination, joint range of motion and assessment of physical endurance and of lung function were completed. In addition, serum and urinary oligosaccharide levels were analysed.
  
  
  METHODS
  In this multicenter longitudinal study clinical data of 43 alpha-Mannosidosis patients were collected. In addition to objective clinical measurements biochemical assays were performed.
  
  
  RESULTS
  Data analysis revealed a wide spectrum of clinical presentation regarding the severity and disease progression. Most clinical abnormalities were observed in the musculoskeletal and neurological system. All patients showed mental retardation and hearing loss from early childhood. An impairment in physical endurance was revealed by the 6-minute walk and 3-minute stair stair climb tests. There was only slight progression of a few clinical findings: Psychiatric troubles in both groups essentially, and respiratory dysfunction under 18 years. The serum and urinary oligosaccharide levels were increased in all affected individuals and correlated well with the 6-minute walk and 3-minute stair climb test results.
  
  
  CONCLUSIONS
  This study confirms that alpha-Mannosidosis is a very heterogeneous disorder regarding both, disease severity and progression. As it has been shown that Mannosidosis patients are able to perform lung function tests and the 6MWT and stair-climb test, these clinical parameters apparently can be used as clinical endpoints for clinical trials. Oligosaccharide levels appeared correlated with functional testing and may serve as biomarkers of disease severity, progression and response to treatment.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier = NCT00498420 and EuropeanCommission FP VI contract LHSM-CT-2006-018692.
authors.affiliation: Center for Pediatric and Adolescent Medicine, University Medical Center, Langenbeckstraße 1, 55131 Mainz, Germany. Michael.Beck@unimedizin-mainz.de
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Olsen
authors.forename: James E
authors.initials: JE
authors.lastname: Wraith
authors.forename: Jiri
authors.initials: J
authors.lastname: Zeman
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Michalski
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
authors.forename: Jens
authors.initials: J
authors.lastname: Fogh
authors.forename: Dag
authors.initials: D
authors.lastname: Malm
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D010807:Physical Endurance; D012129:Respiratory Function Tests; D013429:Sulfatases / Q000097:blood / Q000652:urine; D016138:Walking; D055815:Young Adult; D008363:alpha-Mannosidosis / Q000503:physiopathology*
chemical_list: D013429:Sulfatases; C053174:oligosaccharyl sulfatase