Acid ceramidase deficiency presenting as Farber disease: prospective and retrospective clinical data from an ongoing natural history study
Harmatz P1, Mitchell J2, Lampe C3, Grant C4, Ferreira C R4, Selim L5, Gamal el Din I5, Mungan N6, Bulut F6,
Guelbert N7, Magnusson B8, Sundberg E8, Puri R9, Bijarnia-Makay S9, Kapoor S10, Arslan N11, Makay B11,
DiRocco M12, Ozen S13, Batu E D13, Gokcay G14, Torcoletti M15, Kimura A16, Solyom A17 1UCSF Benioff Children’s Hospital Oakland, Oakland, United States, 2Montreal Children’s Hospital, Montreal, Canada, 3UKGM Universitatsklinikum Giessen, Giessen, Germany, 4Children’s National Medical Center, Washington
DC, United States, 5Cairo University Children’s Hospital, Cairo, Egypt, 6Cukurova University Hospital, Adana, Turkey, 7Children’s Hospital of Cordoba, Cordoba, Argentina, 8Karolinska University Hospital, Stockholm, Sweden, 9Sir Ganga Ram Hospital, New Delhi, India, 10Lok Nayak Hospital, New Delhi, India, 11Dokuz Eylul University Hospital, Izmir, Turkey, 12Istituto Giannina Gaslini, Genoa, Italy, 13Hacettepe University Hospital, Ankara, Turkey, 14Istanbul University, Istanbul, Turkey, 15University of Milan, Milan, Italy, 16Enzyvant, Cambridge, United States, 17Enzyvant, Basel, Switzerland
Background: Farber disease is a rare lysosomal storage disorder caused by mutations in both alleles of the ASAH1
gene. Deficiency of the acid ceramidase enzyme results in the accumulation of the pro-inflammatory and pro-apoptotic sphingolipid ceramide. Typical symptoms include joint disease, subcutaneous nodules, and dysphonia. The broad spectrum of symptom severity may lead to misdiagnosis. This is the first systematic clinical study of the natural history of Farber disease.
Methods/Case Report: The Observational and Cross- Sectional Cohort Study of the Natural History and Phenotypic
Spectrum of Farber Disease (NCT03233841) collects retrospective and prospective data including demographics,
medical and diagnostic history of patients with Farber disease who have or have not undergone hematopoietic stem cell transplantation (HSCT), and specific prospective clinical evaluations (including clinical assessments of subcutaneous nodules, functional tests and patient reported outcomes at baseline, 12 and 36 weeks) in living patients.
Results: From November 2017 to March 2019, 43 patients (26 living, 17 deceased) were enrolled from 15 centers
(9 countries). Selected data from 23 non-HSCT patients alive at baseline: average age was 6.5 years (range 1-28);
88% (21 patients) were less than 18 years old; average number of nodules per patient was 47 (maximum 209); mean childhood health assessment score disability index (CHAQDI) score of 2.48 (14 patients) indicates significant limitation of daily activities.
Results: From November 2017 to March 2019, 43 patients (26 living, 17 deceased) were enrolled from 15 centers
(9 countries). Selected data from 23 non-HSCT patients alive at baseline: average age was 6.5 years (range 1-28);
88% (21 patients) were less than 18 years old; average number of nodules per patient was 47 (maximum 209); mean childhood health assessment score disability index (CHAQDI) score of 2.48 (14 patients) indicates significant limitation of daily activities.
Discussion: The broad phenotypic spectrum of Farber disease, from rapidly progressive (severe), to slowly progressive (attenuated) is represented in the study data. Enrollment indicates that Farber disease is likely not as rare as previously thought. The data confirms that subcutaneous nodules and other typical symptoms are clinically impactful and contribute to expanding and deepening the characterization of Farber disease and potentially to the evaluation of future therapies.
Conflict of Interest declared.
*To download the book of abstracts, please visit https://ssiem2019.org/book-of-abstracts/. Abstract # O-055 found on page 82.