Farber disease is an ultra-rare lysosomal storage disease caused by a mutation in both alleles of the ASAH1 gene, resulting in the deficiency of the lysosomal enzyme acid ceramidase. This leads to the accumulation of the pro-inflammatory sphingolipid ceramide, and a macrophage driven inflammatory process causing the development of typical clinical symptoms. Like many other lysosomal storage diseases, Farber disease has a broad phenotypic spectrum, and is likely underdiagnosed.
Farber patients typically present with the cardinal symptoms of:
Joint contractures or arthritis
Weak or hoarse voice
It may take years for all three cardinal symptoms to appear together, and they may vary greatly in severity. Patients may also present with systemic inflammation (fever), severe pain, peripheral osteolysis, failure to thrive, and developmental delay.
In addition to Farber disease, a mutation in the ASAH1 gene and the resulting acid ceramidase deficiency may also lead to a severe neurological disorder called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) that causes muscle weakness and wasting (atrophy) and a combination of seizures and uncontrollable muscle jerks (myoclonic epilepsy).