Natural history of alpha mannosidosis a longitudinal study

Orphanet Journal of Rare Diseases

Dag Malm³  Jens Fogh¹  Paul Saftig⁶  Jean-Claude Michalski²  Jiri Zeman⁵  James E Wraith⁷  Klaus J Olsen⁸  Michael Beck⁴ 

[1] Zymenex A/S, Roskildevej 12 C, 3400 Hillerød, Denmark;Unite’ Mixte de Recherche CNRS/USTL 8576-UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, IFR 147, Bat C9, Université des Sciences et Technologies de Lille, 59655 Villeneuve d’Ascq Cedex, France;The Tromsø Centre of Internal Medicine (TIS as), House of Health, Sjøgata 31/33, NO9008 Tromsø, Norway;Center for Pediatric and Adolescent Medicine, University Medical Center, Langenbeckstraße 1,55131 Mainz, Germany;Department of Pediatrics, First Faculty of Medicine, Charles University, Ke Karlovu 2, Prague 2 120 00 Czech Republic;Department of Biochemistry, Christian-Albrechts-Universität Kiel, Olshausenstr. 40, 24098 Kiel, Germany;Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, St Mary’s Hospital, Oxford Road, Manchester, M13 9WL, United Kingdom;Larix ApS, Tempovej 44,1, 2750, Ballerup, Denmark

关键词: Survey study;    Oligosaccharides;    Oligosaccharidosis;    Natural history;    Alpha-mannosidosis;   

Others  :  863713
DOI  :  10.1186/1750-1172-8-88

 received in 2013-02-03, accepted in 2013-06-13,  发布年份 2013

【 摘 要 】

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.

Trial registration

ClinicalTrials.gov Identifier = NCT00498420 and EuropeanCommission FP VI contract LHSM-CT-2006-018692.

【 授权许可】

   
2013 Beck et al.; licensee BioMed Central Ltd.

【 图 表 】

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