A cross-sectional quantitative analysis of the natural history of Farber disease: an ultra-orphan condition with rheumatologic and neurological cardinal disease features
PurposeFarber disease (OMIM 22800) is an ultrarare progressive multisystemic neurodevelopmental storage disorder caused by a deficiency of the lysosomal enzyme acid ceramidase (AC). Hard clinical end points for future clinical trials remain to be defined.MethodsWe quantitatively analyzed published c...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2018
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| In: |
Genetics in medicine
Year: 2017, Volume: 20, Issue: 5, Pages: 524-530 |
| ISSN: | 1530-0366 |
| DOI: | 10.1038/gim.2017.133 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/gim.2017.133 Verlag, Volltext: https://www.nature.com/articles/gim2017133 
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| Author Notes: | Matthias Zielonka, Sven F. Garbade, Stefan Kölker, Georg F. Hoffmann & Markus Ries |
| Summary: | PurposeFarber disease (OMIM 22800) is an ultrarare progressive multisystemic neurodevelopmental storage disorder caused by a deficiency of the lysosomal enzyme acid ceramidase (AC). Hard clinical end points for future clinical trials remain to be defined.MethodsWe quantitatively analyzed published cases with Farber disease (N = 96). The main outcome variables were survival and diagnostic delay. As a potential predictor of survival, the influence of residual AC enzyme activity was investigated. The analysis was performed in compliance with STROBE criteria.ResultsThe median survival period of the study population was 3 years. The median age at disease onset was 3 months, and the median age at diagnosis was 17 months. The median diagnostic delay was 13.75 months. Patients with residual AC activity in fibroblasts at more than 5.1% of the normal level survived significantly longer than patients with residual AC activity below this threshold. In addition, higher residual AC activity was associated with a later onset of symptoms.ConclusionFarber disease onset is in infancy. Diagnostic delay is typically substantial. Our data suggest a phenotype-biomarker association with implications for future clinical and therapeutic trials. In the absence of a prospective multicenter natural-history study protocol, we believe that our modeling approach, based on published case descriptions, is the best and most timely approximation for generalizability. |
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| Item Description: | Advance online publication 19 October 2017 Published: 19 October 2017 Gesehen am 16.08.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1530-0366 |
| DOI: | 10.1038/gim.2017.133 |