Farber’s Lipogranulomatosis or Ceramidase Deficiency: Types, Causes, Symptoms, Treatment

Farber’s lipogranulomatosis is also known as ceramidase deficiency, Farber disease and acid ceramidase deficiency.

Farber’s lipogranulomatosis is a rare genetic disease, which involves breaking down and use of fats present in the body. In Farber’s lipogranulomatosis harmful amounts of lipids build up in the tissues and cells all over the body, specifically around the joints of the patient.

Farber’s lipogranulomatosis typically involve signs like a weak cry and a hoarse voice, small lumps of fat below the skin and in other tissues i.e. lipogranulomas, and painful and swollen joints. Apart from this, the patient may also suffer with problems like intellectual disability, an enlarged spleen and liver i.e. hepatosplenomegaly, and difficulty while breathing.

Farber’s lipogranulomatosis is an inherited disease, which passes on to the child if both the parents are carrier of the gene. This pattern of inheritance is known as autosomal recessive. However, the parents who are carriers of the Farber’s lipogranulomatosis gene do not themselves show any signs or symptoms of Farber’s lipogranulomatosis.

• Type 1 Farber’s Lipogranulomatosis or Ceramidase Deficiency: Type 1 Farber’s lipogranulomatosis is the most common type of Farber’s lipogranulomatosis. Type 1 Farber’s lipogranulomatosis involves problems associated with skin, joint, and voice. Lung disease and intellectual disability are often reported by patients of type 1 Farber’s lipogranulomatosis. Infants who are born with type 1 Farber’s lipogranulomatosis usually do not survive beyond early childhood.
• Type 2 and 3 Farber’s Lipogranulomatosis or Ceramidase Deficiency: Type 2 and 3 Farber’s lipogranulomatosis are mild in nature when compared to other types of Farber’s lipogranulomatosis. People affected with the disease have the three classic signs of painful joint deformity, subcutaneous nodules, and hoarseness of voice with sometimes mild intellectual disability. These patients generally are alive for a longer duration than those affected with type 1.
• Type 4 Farber’s Lipogranulomatosis or Ceramidase Deficiency: Type 4 Farber’s lipogranulomatosis involves severe intellectual disability. Type 4 Farber’s lipogranulomatosis leads to life threatening problems starting in infancy because of the massive fat deposition in the lymph nodes, lungs, thymus, spleen, and liver.
• Type 5 Farber’s Lipogranulomatosis or Ceramidase Deficiency: Type 5 Farber’s lipogranulomatosis is usually characterized by progressive declining of central nervous system that may result in intellectual disability, irregular involuntary muscle contraction i.e. myoclonus, paralysis of the legs and arms i.e. quadriplegia, seizures and loss of speech.
• Types 6 and 7 Farber’s Lipogranulomatosis or Ceramidase Deficiency: Types 6 and 7 usually involve few other disorders along with the regular problems characteristic of Farber’s lipogranulomatosis.

Farber’s lipogranulomatosis is a rare disease.

• Approximately 80 cases of Farber’s lipogranulomatosis have been reported worldwide.
• Infants often get affected with it.
• Farber’s lipogranulomatosis affects both men and women.

Farber’s lipogranulomatosis is caused due to mutations in the ASAH1 gene. The ASAH1 gene is a gene that gives instructions for production of an enzyme known as acid ceramidase. Acid ceramidase is present in the compartments, which digest and recycle materials in the cell by breaking down the fats known as ceramides for the purpose of getting them used by the body.

The building up of the ceramide in Farber’s lipogranulomatosis is caused due to failure of breaking down of ceramides in lysosomes. ASAH1 gene mutations result in storing the functional acid ceramidase that stops the lysosomes from appropriate breaking down of ceramides. Lack of activity of acid ceramidase can develop ceramides in the lysosomes of tissues and cells in the colon, muscles used for movement, bone, cartilage, lung and liver. The severity of the disease varies from mild to severe depending upon the amount of ceramide that has accumulated in the body.

• Hoarseness in voice.
• Swollen joints and lymph nodes.
• Impaired motor and mental ability.
• Difficulty while swallowing.
• Vomiting.
• Arthritis.
• Inflammatory nodules in the lungs and interstitial pneumonitis.
• Nodules beneath the skin and the lungs or body parts are also occasionally seen.
• Chronic shortening of tendons and muscles surrounding the joints.
• Enlargement of spleen and liver.

There is no proper cure available for treating Farber’s lipogranulomatosis. However, corticosteroids may help in relieving the pain. Bone marrow transplants help in improving the small masses of inflamed tissue in patients with less or no nervous system or lung problems. Surgical removal or reduction of granulomas is often done in case of older patients.

Clinical trial of painful joint deformity, subcutaneous nodules especially near the joints and on pressure points, and hoarseness is the typical presentation of Farber’s lipogranulomatosis. Diagnosis of the disease is confirmed by determination of acid ceramidase activity.

Diagnostic tests include:

• Genetic test.
• Biopsy.