What is acid ceramidase deficiency?
Acid ceramidase deficiency is an umbrella term which includes a spectrum of conditions including Farber Disease and SMA-PME. ACD manifesting as Farber Disease, is a lysosomal storage disorder. Lysosomal storage diseases are inherited metabolic errors that result in the lack or malfunction of a particular enzyme. The enzyme is needed to break down complex compounds, such as excess lipid (fat) within lysosomes, which are cellular structures responsible for digesting and recycling materials. Without enough enzyme, the material is not broken down and builds up to harmful amounts..
In acid ceramidase deficiency, the body does not make enough of the enzyme acid ceramidase, which is normally found in lysosomes and breaks down a fatty substance called ceramide. Without ceramidase, ceramide accumulates in cells all over the body, affecting the joints, liver, lungs, nervous system and more.
Acid ceramidase deficiency is a very rare disease, with only approximately 80 cases of the Farber Disease manifestation reported in medical literature to date. ACD including SMA-PME brings that number up to over 200 cases as of 2018(Yu 2018). It affects males and females in equal numbers and has a broad presentation. The onset of symptoms may occur in infancy, childhood or adulthood.
What are the symptoms of acid ceramidase deficiency manifesting as Farber Disease?
Acid ceramidase deficiency is usually recognized by three characterizing symptoms:
- Painful and progressive deformity in the joints
- Nodules under the skin
- Progressive hoarseness and/or a weak cry
Other symptoms may also appear, including:
- Poor weight gain
- Difficulty breathing
- Developmental delay
- Diminished muscle tone
- Moderately enlarged liver and spleen
- Moderate swelling in lymph nodes
- Impaired vision
What causes acid ceramidase deficiency?
Acid ceramidase deficiency is caused by mutations in the ASAH1 gene. This gene is responsible for the production of the acid ceramidase enzyme. Alterations in the ASAH1 gene result in abnormally low enzyme levels and a toxic accumulation of ceramide.
The disease is inherited in an autosomal recessive manner, which means the condition does not appear unless a person inherits a mutation in the ASAH1 gene from both parents.
Researchers have determined the location of the ASAH1 gene: chromosome 8, region 8p22-821.3. Chromosomes carry the genetic characteristics of individuals, contain thousands of genes each, and are located in the nucleus of all body cells. Human body cells normally have 23 pairs of chromosomes, so 46 chromosomes in total. Each chromosome has a short arm designated “p” and a long arm designated “q,” and then is divided even more into numbered bands. In this instance, the location of the mutated gene is a region on the short arm of chromosome 8, between bands 21.3 and 22.
How is acid ceramidase deficiency diagnosed?
Acid ceramidase deficiency is diagnosed using the following procedures:
- Prenatal diagnosis is possible in the fifteenth to sixteenth week of pregnancy via amniocentesis (testing cells taken from the fluid in the water sac surrounding the fetus)
- Physical exam that notices characterizing symptoms
- Genetic testing
- Enzyme activity assay
What are the treatments for acid ceramidase deficiency?
There is no cure for acid ceramidase deficiency, so treatment focuses on pain relief and targeting specific symptoms. This includes, but is not limited to:
- Anti-inflammatory medications, such as corticosteroid drugs to relieve joint pain
- Bone marrow transplant to improve skin and joint problems
- Surgical removal of nodules
- Genetic counseling