Ultra-orphan lysosomal storage diseases: a cross-sectional quantitative analysis of the natural history of alpha-mannosidosis
Purpose Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disorder caused by a deficiency of the enzyme alpha-mannosidase. Recently, enzyme replacement therapy was approved in the European Union for the treatment of alpha-mannosidosis, but evaluation regarding long-term efficacy and safet...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 June 2019
|
| In: |
Journal of inherited metabolic disease
Year: 2019, Volume: 42, Issue: 5, Pages: 975-983 |
| ISSN: | 1573-2665 |
| DOI: | 10.1002/jimd.12138 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1002/jimd.12138 Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/jimd.12138 
|
| Author Notes: | Matthias Zielonka, Sven F. Garbade, Stefan Kölker, Georg F. Hoffmann, Markus Ries |
| Summary: | Purpose Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disorder caused by a deficiency of the enzyme alpha-mannosidase. Recently, enzyme replacement therapy was approved in the European Union for the treatment of alpha-mannosidosis, but evaluation regarding long-term efficacy and safety is hard to assess due to missing quantitative natural history data, in particular survival. Methods We performed a quantitative analysis of published cases (N=111) with alpha-mannosidosis. Main outcome measures were age of disease onset, diagnostic delay and survival (overall and by subgroup exploration). Residual alpha-mannosidase activity and age of onset were explored as potential predictors of survival. STROBE criteria were respected. Results Median age of onset was 12 months. Median diagnostic delay was 6 years. At the age of 41 years 72.3% of patients were alive (N=111). Residual alpha-mannosidase activity (N=34) predicted survival: Patients with a residual alpha-mannosidase activity below or equal to 4.5% of normal in fibroblasts had a median survival of 3.5 years, whereas patients with alpha-mannosidase activity above this threshold all survived during the observation period reported. Patients with age of onset above 7 years survived significantly longer than patients with age of onset below or equal to 7 years. Patient distribution was panethnic with hotspots in the USA and Germany. Synopsis We defined age of onset, diagnostic delay and survival characteristics in a global cohort of 111 patients with alpha-mannosidosis by retrospective quantitative natural history modeling. These data expand the quantitative understanding of the clinical phenotype. This article is protected by copyright. All rights reserved. |
|---|---|
| Item Description: | Gesehen am 30.10.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1573-2665 |
| DOI: | 10.1002/jimd.12138 |