Enzyvant is partnering with PerkinElmer Genomics to support no-cost genetic testing of the ASAH1 gene to support diagnosis of patients with acid ceramidase deficiency. Enzyvant is a biopharmaceutical company focused on developing transformative therapies for patients with rare diseases.

About Acid Ceramidase Deficiency

Acid ceramidase deficiency is a spectrum of clinical diseases that includes Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). Both manifestations are autosomal recessive lysosomal storage disorders caused by mutations in the ASAH1 gene which leads to the deficiency of the acid ceramidase enzyme. This deficiency leads to the accumulation of the sphingolipid ceramide within cells. Like other lysosomal storage disorders, Farber disease and SMA-PME represent a broad spectrum of symptoms and disease severity and are progressive in nature1,2.

Farber Disease

Acid ceramidase deficiency manifesting as Farber disease is characterized by cardinal symptoms that include:

  •     subcutaneous nodules
  •     joint swelling/arthritis
  •     hoarse or weak voice

Additional symptoms may also include impaired cognitive development due to brain involvement as well as impact on lungs, liver and bones (osteolysis). Disease onset is usually in early childhood but may occur later in life. In its most rapidly progressive form, many patients with Farber disease do not live beyond the age of two years1.

More slowly progressive forms of Farber disease are susceptible to misdiagnosis due to symptoms which overlap with other diseases and is likely under-represented in the medical literature3. Farber disease should be suspected in patients presenting with any combination of the cardinal symptoms, or patients exhibiting an overlapping pattern of neurological and rheumatological manifestations1.


SMA-PME (Spinal Muscular Atrophy with Progressive Myoclonic Epilepsy)

SMA-PME is a neurological phenotype of acid ceramidase deficiency almost always without rheumatologic manifestations. Neurologic symptoms can present during childhood after a period of normal development. Symptoms resemble those of other types of SMA, including loss of coordination, difficulty with ambulation, falls due to proximal muscle weakness, tremors, and lower motor neuron disease. A myoclonic seizure disorder may develop that includes a variety of seizure types that can be refractory to treatment. Epilepsy or SMA may develop first and either may be present for years before the other becomes evident. Therefore, acid ceramidase deficiency should be part of the differential diagnosis of children or young adults with progressive myoclonic epilepsy syndromes as well as those with spinal muscular atrophy1.

Diagnosis

To facilitate earlier diagnosis, no-cost genetic sequencing and deletion/duplication testing is available for the ASAH1 gene for those patients suspected of having acid ceramidase deficiency that presents as Farber disease or SMA-PME.

When to consider testing:

Consider ASAH1 gene testing for:

  •     Any patients that demonstrate an overlap of rheumatologic and neurologic symptoms
  •     Any patients with a history of juvenile idiopathic arthritis (JIA) and at least one of the following symptoms:
    •     Failure to respond to multiple biologic therapies
    •     Subcutaneous nodules
    •     Chronic joint contractures
    •     Dysphonia
    •     Neurologic symptoms
    •     Peripheral osteolysis4
  •     Any patients with progressive myoclonic epilepsy and/or spinal muscular atrophy

No-cost ASAH1 gene testing

Please provide the following information when placing your order:

  • Name and position of person placing kit request
  • Ordering physician
  • Institution
  • City, state
  • Email and phone contacts
  • Number of patients requiring testing/number of kits requested
  • Any additional relevant information

Order no-cost ASAH1 gene testing

Specimen instructions:

Result information:
Results are sent from PerkinElmer Genomics to the ordering physician within 14-21 days. No result or patient identifying data is shared with Enzyvant.

References

  1.  Yu, F. P., Amintas, S., Levade, T., & Medin, J. A. (2018). Acid ceramidase deficiency: Faber disease and SMA-PME. Orphanet Journal of Rare Diseases, 121.
  2.  Schuchman, E. H. (2016). Acid ceramidase and the treatment of ceramide diseases: The expanding role of enzyme replacement therapy. Biochemica et Biophysica Acta, 1459-1471.
  3.  Huele, B., Mueller, L., & Levade, T. (2014). Why Farber Disease May be Misdiagnosed as Juvenile Idiopathic Arthritis. The Rheumatologist, 8, 35. Retrieved from www. the-rheumatologist. org/article/why-farber-disease-may-be-misdiagnosed-as-juvenile-idiopathic-arthritis/
  4. Bonafé L, Kariminejad A, Li J, Royer-Bertrand B, Garcia V, Mahdavi S, Bozorgmehr B, Lachman R, Mittaz-Crettol L, Campos-Xavier B, Nampoothiri S, Unger S, Rivolta C, Levade T, Superti-Furga A. (2016). Peripheral osteolysis in adults linked to ASAH1 (acid ceramidase) mutations: A new presentation of Farber’s disease. Arthritis Rheumatol, 68 (9):2323-7.