A cross-sectional quantitative analysis of the natural history of Farber disease

• Verfasst von: Zielonka, Matthias [VerfasserIn]
• Verfasst von: Garbade, Sven [VerfasserIn]
• Verfasst von: Kölker, Stefan [VerfasserIn]
• Verfasst von: Hoffmann, Georg Friedrich [VerfasserIn]
• Verfasst von: Ries, Markus [VerfasserIn]
• Titel: A cross-sectional quantitative analysis of the natural history of Farber disease
• Titelzusatz: an ultra-orphan condition with rheumatologic and neurological cardinal disease features
• Verf.angabe: Matthias Zielonka, Sven F. Garbade, Stefan Kölker, Georg F. Hoffmann & Markus Ries
• Jahr: 2018
• Jahr des Originals: 2017
• Umfang: 7 S.
• Fussnoten: Advance online publication 19 October 2017 ; Published: 19 October 2017 ; Gesehen am 16.08.2018
• Titel Quelle: Enthalten in: Genetics in medicine
• Ort Quelle: London, UK : Springer Nature, 1998
• Jahr Quelle: 2018
• Band/Heft Quelle: 20(2018), 5, Seite 524-530
• ISSN Quelle: 1530-0366
• DOI: doi:10.1038/gim.2017.133
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580124267

Abstract

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.