Farber disease

Farber disease, also known as Farber lipogranulomatosis or acid ceramidase deficiency, is an extremely rare autosomal recessive lysosomal storage disorder caused by mutations in the ASAH1 gene, which encodes the enzyme acid ceramidase. This enzyme is responsible for breaking down ceramide, a fatty substance (lipid) found in cells. When acid ceramidase is deficient or absent, ceramide accumulates in various tissues throughout the body, leading to progressive damage. The classic triad of symptoms includes painful and progressively swollen joints (arthropathy), subcutaneous nodules (lipogranulomas) that develop near joints and over pressure points, and a progressive hoarseness of the voice due to laryngeal involvement. The disease affects multiple body systems, including the musculoskeletal system, skin, respiratory tract, nervous system, liver, and spleen. In severe forms, the central nervous system is significantly affected, leading to progressive neurological deterioration. The severity and age of onset vary considerably, with the most severe forms presenting in the neonatal or early infantile period and leading to death within the first few years of life. Milder forms may present later in childhood with predominantly joint and subcutaneous involvement and relatively preserved neurological function. Currently, there is no cure or specific enzyme replacement therapy approved for Farber disease. Treatment is primarily supportive and symptomatic, including pain management, physical therapy, and surgical removal of nodules when they cause functional impairment. Hematopoietic stem cell transplantation (HSCT) has been attempted in some patients, particularly those without severe neurological involvement, and has shown some benefit in reducing nodules and joint symptoms. Gene therapy and recombinant enzyme replacement approaches are under investigation. Prognosis depends on disease severity, with the most severe forms being fatal in early childhood.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Farber disease