Contents
Lysosomal storage disorder caused by acid ceramidase deficiency and associated with distinct clinical phenotypes.
- Autosomal recessive inheritance
History:
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:
- Joint stiffness & deformation
- Prominent subcutaneous nodules
- Progressive hoarseness (d/t laryngeal involvement)
Diagnosis
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