A132: Farber Disease Explains Subset of Juvenile Idiopathic Arthritis

Abstract

Background/Purpose:Farber Lipogranulomatosis (Farber Disease; FD) is an ultra‐;rare lysosomal storage disorder due to the inherited deficiency of the enzyme acid ceramidase, and the resultant accumulation of the lipid substrate, ceramide. Ceramide is a proinflammatory and pro‐;apoptotic lipid that has been implicated in the pathogenesis of cartilage disorders. Farber Disease has a heterogeneous presentation ranging from a severe phenotype with respiratory and CNS involvement with an average life expectancy of 1.3 years (Type 1) to a moderate phenotype which generally includes joint swelling, contractures and pain (Type 3). Awareness of FD in the pediatric arthritis community is limited due to the rarity of the disease. The clinical similarity between the moderate Farber phenotype and Juvenile Idiopathic Arthritis (JIA) suggests that moderate Farber Disease cases would be classified as JIA cases.Methods:To test the hypothesis that moderate Farber Disease is diagnosed as Juvenile Idiopathic Arthritis, we conducted a literature search of Farber Disease case studies since 1990 using search terms “Farber Disease,” “Farber's Disease” and “Farber lipogranulomatosis” in PubMed published in English. Moderate Farber Disease patients were defined as surviving into their third year of life without hepatosplenomegally or significant neurological involvement. Cases where idiopathic arthritis was suspected were noted.Results:The literature search identified 84 unique papers with 35 comprising Farber Disease case studies. Of the overall case studies, 14 or 40% described patients with moderate disease. Five or 36% of these patients were diagnosed as having Juvenile Idiopathic Arthritis.Conclusion:A high percentage of moderate Farber Disease patients are diagnosed as having Juvenile Idiopathic Arthritis. Several of the patients described were referred to secondary or tertiary centers for treatment, which suggests that this percentage may be understated. Given this finding, it is important to increase the awareness of Farber Disease in the pediatric rheumatology community. Differential diagnosis can be made by accounting for the comparatively early onset of FD, the progressive severity of arthritis in FD, the presence of subcutaneous nodules in the joints, scalp and/or spine of FD patients and an unusual, hoarse cry or voice in FD patients, whichi is due to nodule formation on the larynx. Plexcera Therapeutics LLC is a new company focused on developing acid ceramidase enzyme therapy for disorders with ceramide accumulation (www.plexcera.com). Based on experience with bone marrow transplant in Farber Disease patients, enzyme replacement therapy could resolve arthritis phenotype in patients. We propose that FD can account for specific cases of JIA, and that genetic screening of the JIA population will reveal FD patients that will benefit from future treatment with rhAC.