Farber's disease is a rare inherited condition involving the breakdown and use of fats in the body (lipid metabolism). In affected individuals, lipids accumulate abnormally in cells and tissues throughout the body, particularly around the joints. The deficiency of an enzyme is called ceramidase resulting in the harmful accumulation of certain chemicals in the body which causes damage and inflammation.
Three classic signs occur in Farber lipogranulomatosis: a hoarse voice or a weak cry, small lumps of fat under the skin and in other tissues (lipogranulomas), and swollen and painful joints. Affected individuals may also have difficulty breathing, an enlarged liver and spleen (hepatosplenomegaly), and developmental delay.
Researchers have described seven types of Farber lipogranulomatosis based on their characteristic features:
Type 1 is the most common, or classical, form of this condition and is associated with the classic signs of voice, skin, and joint problems that begin a few months after birth. Developmental delay and lung disease also commonly occur. Infants born with type 1 Farber lipogranulomatosis usually survive only into early childhood.
Types 2 and 3 generally have less severe signs and symptoms than the other types. Affected individuals have the three classic signs and usually do not have developmental delay. Children with these types of Farber lipogranulomatosis typically live into mid- to late childhood.
Types 4 and 5 are associated with severe neurological problems. Type 4 usually causes life-threatening health problems beginning in infancy due to massive lipid deposits in the liver, spleen, lungs, and immune system tissues. Children with this type typically do not survive past their first year of life. Type 5 is characterized by progressive decline in brain and spinal cord (central nervous system) function, which causes paralysis of the arms and legs (quadriplegia), seizures, loss of speech, involuntary muscle jerks (myoclonus), and developmental delay. Children with type 5 Farber lipogranulomatosis survive into early childhood.
Types 6 and 7 are very rare, and affected individuals have other associated disorders in addition to Farber lipogranulomatosis.
- hoarse voice or weak cry
- small lumps of fat under the skin and in other tissues (lipogranulomas)
- swollen and painful joints
- Joint swelling
- Limitation of joint mobility
- Short stature
- Psychomotor deterioration
- Subcutaneous nodules
- Failure to thrive
- Mental retardation
- Enlarged liver and spleen
- Painful joint swelling
- Joint deformity
- Breathing difficulty
- Failure to thrive
- Cherry-red macular spots
- Eye granulomas
- Impaired deep tendon reflexes
- Impaired psychomotor development
This condition is caused by mutations in the ASAH1 gene and is inherited in an autosomal recessive manner. The ASAH1 gene provides instructions for making an enzyme called acid ceramidase. This enzyme is found in cell compartments called lysosomes, which digest and recycle materials. Acid ceramidase breaks down fats called ceramides into a fat called sphingosine and a fatty acid. These two breakdown products are recycled to create new ceramides for the body to use. Ceramides have several roles within cells. For example, they are a component of a fatty substance called myelin that insulates and protects nerve cells.
- Currently, there are no specific methods or guidelines to prevent Farber’s Disease genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
Normally, a case of Farber’s Disease is easily recognized from its distinct clinical presentations and on studying the family history. The 3 key features that are basically used to confirm the disease are:
- Sub-surface skin nodules (subcutaneous nodules)
- Joint deformities
- Hoarseness of voice
Nevertheless, differential diagnostic tests may be required to rule out other lysosomal storage deficiencies. Some of the exams and tests conducted include:
- Skin biopsy - the specimen is examined under a microscope by a pathologist to arrive at a definitive diagnosis
- Genetic analysis to detect abnormal gene
- Prenatal diagnosis (during pregnancy), using amniocentesis
- Blood tests, such as complete blood count
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
Most children with Farber disease die by age 2, usually from lung disease. In one of the most severe forms of the disease, an enlarged liver and spleen (hepatosplenomegaly) can be diagnosed soon after birth. Children born with this form of the disease usually die within 6 months.
There is no specific treatment for Farber disease. Corticosteroids may be prescribed to relieve pain. Bone marrow transplants may improve granulomas (small masses of inflamed tissue) on patients with little or no lung or nervous system complications. Older patients may have granulomas surgically reduced or removed.
Refer to research Publications.