Acid ceramidase (N-acylsphingosine amidohydrolase 1) (ACDase; ASAH1)

Acid ceramidase (ACDase) is a lysosomal enzyme encoded by the ASAH1 gene that catalyzes the breakdown of ceramide, a bioactive lipid, into sphingosine and free fatty acid.[1][6][8] Mutations in ASAH1 cause deficiency of this enzyme, leading to pathological accumulation of ceramide in various tissues and triggering a spectrum of rare disorders collectively termed acid ceramidase deficiency.[1][2] The two primary manifestations are Farber disease, characterized by the classical triad of subcutaneous nodules, joint contractures, and voice hoarseness with potential multi-organ involvement, and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME), featuring progressive muscle weakness and drug-resistant seizures.[1][2][5] Fewer than 200 cases have been reported in the literature.[1] Currently, there is no cure, with treatment focused on symptom management and, in rare cases, hematopoietic stem cell transplantation for non-neurologic aspects.[1][6] ACDase restoration through gene therapy or enzyme replacement represents a theoretical therapeutic approach, though no disease-modifying treatments are currently available.

Other names

Farber lipogranulomatosis enzymeceramidase deficiencyacid N-acylsphingosine amidohydrolase 1N-acylsphingosine amidohydrolase

Enzyme replacement or restoration of ACDase activity to reduce ceramide accumulation