Farber's disease E75.2

Sidney Farber, 1952

Very rare, autosomal recessive inherited lysosomal storage disease caused by a (point) mutation of the ASAH gene The ASAH gene codes for the enzyme "acid ceramidase" which is located on chromosome 8 gene locus p22-p21.3. The enzyme is also known as N-acylsphingosine amidohydroxylase or acronymically as ASAH.

Mutations of the ASAH gene cause a lack of activity of the acid ceramidase. The acid ceramidase is a hydrolase localised in the lysosomes which catalyses the cleavage of ceramides into sphingosine and fatty acids. The enzyme's lack of activity caused by the mutation leads to an intracellular accumulation of toxic ceramide.

Depending on the patient and the degree of lack of activity very different clinic. First symptoms possible already in infancy, a 2nd manifestation peak is puberty. Thus also different course, depending on the time of first appearance of the symptoms.

The clinical picture is mainly characterized by contractures of the joints, periarticular subcutaneous nodules, short stature (hyposomia), anomalies of the larynx (laryngomalacia), corneal opacities. Enlargements of the liver and/or spleen are not uncommon. Recurrent respiratory tract infections are complicating and life-limiting.

Clinic; measurement of ceramidase activity; detection of the mutation

No causal therapy available. Symptomatic therapy.