Farber disease is one of the rarest forms of lysosomal diseases; it is caused by a deficiency in the lysosomal enzyme acid ceramidase, which hydrolyses ceramide to form sphingosine and fatty acids. The deficiency of acid ceramidase leads to the deposition of glycolipid ceramide in different tissues. Clinical features include periarticular subcutaneous nodules, contractures, hoarseness, neurological symptoms, and sometimes hepatosplenomegaly.
Mutations in the gene ASAH1, which encodes N-acylsphingosine amidohydrolase (acid ceramidase) 1 were found to cause Farber disease. Such mutations cause enzymatic deficiency and therefore a defect in the synthesis and degradation of ceramide leading to intracellular accumulation of ceramides in the joints, tissues, and central nervous system.