Farber Disease (Acid Ceramidase Deficiency): The First Natural History Study of This Rare Disease Involving Symptoms Which Can Mimic JIA

Alexander Solyom¹, Erik Sundberg ², John Mitchell ³, Christina Grant ⁴, Carlos Ferreira ⁵, Paul Harmatz ⁶, Neslihan Mungan ⁷, Fatma Bulut ⁷, Christina Lampe ⁸, Andreas Hahn ⁸, Norberto Guelbert ⁹, Nur Arslan ¹⁰, Balahan Makay ¹⁰, Ratna Puri ¹¹, Sunita Bijarnia-Mahay ¹¹, Laila Selim ¹², Iman Gamal el Din ¹², Seema Kapoor ¹³, Maja DiRocco ¹⁴, Seza Ozen ¹⁵, Ezgi Batu ¹⁵, Gulden Gokcay ¹⁶, Marta Torcoletti ¹⁷, Alan Kimura ¹⁸ and Bo Magnusson ², ¹Enzyvant, Basel, Switzerland, ²Karolinska University Hospital, Stockholm, Sweden, ³Montreal Children's Hospital, Montreal, Canada, ⁴Children's National Medical Center, Washingotn, DC, ⁵Children's National Medical Center, Washington, DC, ⁶UCSF Benioff Children's Hospital Oakland, Oakland, CA, ⁷Cukurova University Hospital, Adana, Turkey, ⁸University Hospital Giessen, Giessen, Germany, ⁹Children's Hospital of Cordoba, Cordoba, Argentina, ¹⁰Dokuz Eylul University Hospital, Izmir, Turkey, ¹¹Sir Ganga Ram Hospital, Delhi, India, ¹²Cairo University Children's Hospital, Cairo, Egypt, ¹³13Lok Nayak Hospital and Maulana Azad Medical College, Delhi, India, ¹⁴Istituto Giannina Gaslini, Genoa, Italy, ¹⁵Hacettepe University Hospital, Ankara, Turkey, ¹⁶Istanbul University, Istanbul, Turkey, ¹⁷University of Milan, Milan, Italy, ¹⁸Enzyvant, Cambridge, MA

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ASAH1, Farber disease, juvenile idiopathic arthritis (JIA), natural history and disease burden

Session Information

Date: Tuesday, November 12, 2019

Title: Pediatric Rheumatology – ePoster III: Systemic JIA, Fever, & Vasculitis

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: The cardinal clinical symptoms of Farber disease (arthritis/contractures, subcutaneous granulomatous nodules, dysphonia) may be misdiagnosed as JIA. Mutations in the ASAH1 gene and the resulting deficiency of the lysosomal enzyme acid ceramidase leads to accumulation of the pro-inflammatory sphingolipid ceramide, causing a broad spectrum of disease severity and presentation of symptoms, which may delay diagnosis or lead to misdiagnosis. This study represents the first comprehensive, systematic collection of retrospective and prospective clinical data on the natural history of Farber disease.

Methods: The Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease (NCT03233841) is collecting retrospective and prospective data, including demographics, clinical presentation, phenotype, and diagnostic history, of patients diagnosed with Farber disease who have or have not undergone hematopoietic stem cell transplantation (HSCT). This data, along with specific prospective clinical evaluations in living patients, will be communicated.

Results: Since November 2017, 43 patients (26 living, 17 deceased) have been enrolled in the study. To date, patients have been enrolled at 15 centers in 9 countries. In patients whose data was available for analysis, the average age of the living patients is 9 years (range 1 to 28 years), and the average time from onset of first symptoms to diagnosis is 2 years (range < 1 to 12 years). Of the non-HSCT patients, 32% were treated with a biologic. Childhood Health Assessment Questionnaire Disability Index Scores (CHAQ DI) ranged from 1.25 to 3 across the non-HSCT population (n=14), including those patients treated with DMARDs and/or biologics.

Conclusion: Among patients representing the broad phenotypic spectrum of Farber disease, from rapidly progressive (severe) to slowly progressive (attenuated), the data confirms that patients can be misdiagnosed as having JIA, and that there is a high disease-related burden as demonstrated by the CHAQ DI scores, which symptomatic treatment with biologics does not resolve. Demographic information and numbers of patients enrolled indicate that Farber disease is likely not as rare as previously thought.

Disclosure: A. Solyom, Enzyvant, 3, 4; E. Sundberg, Enzyvant, 9; J. Mitchell, Enzyvant, 9; C. Grant, None; C. Ferreira, None; P. Harmatz, None; N. Mungan, None; F. Bulut, None; C. Lampe, None; A. Hahn, None; N. Guelbert, None; N. Arslan, None; B. Makay, None; R. Puri, None; S. Bijarnia-Mahay, None; L. Selim, None; I. Gamal el Din, None; S. Kapoor, None; M. DiRocco, None; S. Ozen, Enzyvant, 8; E. Batu, None; G. Gokcay, None; M. Torcoletti, None; A. Kimura, Enzyvant, 3, 4; B. Magnusson, None.

To cite this abstract in AMA style:

Solyom A, Sundberg E, Mitchell J, Grant C, Ferreira C, Harmatz P, Mungan N, Bulut F, Lampe C, Hahn A, Guelbert N, Arslan N, Makay B, Puri R, Bijarnia-Mahay S, Selim L, Gamal el Din I, Kapoor S, DiRocco M, Ozen S, Batu E, Gokcay G, Torcoletti M, Kimura A, Magnusson B. Farber Disease (Acid Ceramidase Deficiency): The First Natural History Study of This Rare Disease Involving Symptoms Which Can Mimic JIA [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/farber-disease-acid-ceramidase-deficiency-the-first-natural-history-study-of-this-rare-disease-involving-symptoms-which-can-mimic-jia/. Accessed .

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