Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Bonafé, Luisa and Kariminejad, Ariana and Li, Jia and Royer-Bertrand, Beryl and Garcia, Virginie and Mahdavi, Shokouholsadat and Bozorgmehr, Bita and Lachman, Ralph L. and Mittaz-Crettol, Lauréane and Campos-Xavier, Belinda and Nampoothiri, Sheela and Unger, Sheila and Rivolta, Carlo and Levade, Thierry and Superti-Furga, Andrea. (2016) Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease. Arthritis & rheumatology, 68 (9). pp. 2323-2327.

[img] PDF
Restricted to Repository staff only


Official URL: https://edoc.unibas.ch/81707/

Downloads: Statistics Overview


To establish a diagnosis and provide counseling and treatment for 3 adult patients from one family presenting with peripheral osteolysis.; Following clinical and radiographic assessment, exome sequencing, targeted gene resequencing, and determination of enzyme activity in cultured fibroblasts were performed.; The proband (age 40 years) had a history of episodic fever and pain in childhood that subsided around puberty. He and 2 of his older sisters (ages 58 and 60 years, respectively) showed adult-onset progressive shortening of fingers and toes with redundancy of the overlying skin. Radiographs showed severe osteolysis of the distal radius and ulna, carpal bones, metacarpal bones, and phalanges. Sequencing of the known genes for recessively inherited osteolysis, MMP2 and MMP14, failed to show pathogenic mutations. Exome sequencing revealed compound heterozygosity for mutations c.505T>C (p.Trp169Arg) and c.760A>G (p.Arg254Gly) in ASAH1, the gene coding for acid ceramidase. Sanger sequencing confirmed correct segregation in the family, and enzyme activity in fibroblast cultures from the patients was reduced to ∼8% of that in controls, confirming a diagnosis of Farber's disease.; Our findings indicate that hypomorphic mutations in ASAH1 may result in an osteoarticular phenotype with a juvenile phase resembling rheumatoid arthritis that evolves to osteolysis as the final stage in the absence of neurologic signs. This observation delineates a novel type of recessively inherited peripheral osteolysis and illustrates the long-term skeletal manifestations of acid ceramidase deficiency (Farber's disease) in what appear to be the oldest affected individuals known so far.
Faculties and Departments:03 Faculty of Medicine
09 Associated Institutions > Institute of Molecular and Clinical Ophthalmology Basel (IOB)
UniBasel Contributors:Rivolta, Carlo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American College of Rheumatology
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
edoc DOI:
Last Modified:12 May 2021 13:40
Deposited On:19 Mar 2021 11:25

Repository Staff Only: item control page