Fibrocytic dysmucopolysaccharidosis

Genetics

Variants in the ASAH1 gene, which codes for acid ceramidase, cause Farber disease. Affected individuals inherit two non‑functioning copies of this gene, one from each parent; each parent is a carrier with one functional and one non‑functional copy.

Siblings have a 25% chance of having the disease, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. No definitive genotype‑phenotype correlations are known. The ASAH1 gene also causes spinal muscular atrophy with progressive myoclonic epilepsy (SMA‑PME), and some individuals have overlapping symptoms of both disorders.

Diagnosis

Disease onset is typically in early infancy, though later onset can occur. Classic symptoms appear within the first weeks to months of life; moderate or attenuated forms may develop at any time in childhood. Symptoms can be misdiagnosed as Juvenile Idiopathic Arthritis. Diagnosis is confirmed by molecular genetic testing of the ASAH1 gene or by measuring acid ceramidase enzyme activity.

Treatment

No disease‑specific treatment exists. The anti‑inflammatory drug tocilizumab, an interleukin‑6 receptor inhibitor, has improved inflammation and pain in some patients.

Bone marrow transplant may reduce granulomas and inflammation in patients with little or no lung or nervous system involvement. Supportive therapies include physical therapy, respiratory support, and mobility aids. Enzyme replacement therapy has shown proof‑of‑concept in cells and mice, and an investigational therapy is being developed with a clinical study planned.