P 781. A Cross-sectional Quantitative Analysis of the Natural History of Farber Disease: An Ultra-Orphan Condition with Rheumatologic and Neurological Cardinal Disease Features

Purpose: Farber’s 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.

Methods: We quantitatively analyzed published cases with Farber’s 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.

Results: The 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.

Conclusion: Farber’s 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.