Internal Medicine

Farber disease (FD)

Lysosomal storage disorder caused by acid ceramidase deficiency and associated with distinct clinical phenotypes.

Lysosomal storage disorder caused by acid ceramidase deficiency and associated with distinct clinical phenotypes.

  • Autosomal recessive inheritance


Dr. Sidney Farber described the first case of “disseminated lipogranulomatosis” in a 14-month-old infant at a Mayo Foundation lecture in 1947. Farber later published a case series of three patients in 1952, as a transaction for the 62nd annual meeting of the American Pediatric Society. He later expanded the descriptions in 1957. Farber originally hypothesized that the disease shared the lipid storage aspects of Niemann-Pick disease as well as the inflammation observed in Hand-Schüller-Christian disease. Although Farber demonstrated an increase in lipids in his early biochemical studies, the main lipid that accumulates in Farber disease (FD), i.e., ceramide, was not identified until 1967, when it was isolated from a biopsy of a patient’s kidney. Acid ceramidase (ACDase), which was first purified in 1963, catalyzes the synthesis and degradation of ceramide into sphingosine and fatty acid. In 1972, Sugita and colleagues established that ACDase activity was not detectable in post-mortem tissue from a FD patient. In 1996, the ASAH1 gene that encodes ACDase was fully sequenced and characterized.

Clinical features

Clinical triad:

  1. Joint stiffness & deformation
  2. Prominent subcutaneous nodules
  3. Progressive hoarseness (d/t laryngeal involvement)
The typical clinical manifestations by organ type that have been reported in cases of Farber Disease (FD) and SMA-PME in the published literature. FD symptoms organized by neurological symptoms, ophthalmic symptoms, cardinal triad symptoms, respiratory symptoms, hematopoietic symptoms, gastrointestinal involvement, dermatological manifestations, liver disease, motor neuron and muscle weakness, and bone disease phenotypes | Yu, F., Amintas, S., Levade, T., & Medin, J. A. (2018). Acid ceramidase deficiency: Farber disease and SMA-PME. Orphanet journal of rare diseases, 13(1), 121.


Acid ceramidase activity :

Measured in cultured skin fibroblasts, white blood cells or amniocytes
  • < 6% of control values

Tissue biopsy:

Typical histopathologic features
  • Granulomas with macrophages containing lipid cytoplasmic inclusions in subcutaneous nodules or other tissues

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