Farber's disease is a rare inherited metabolic disorder. It is one of the diseases known as lysosomal storage diseases. These are inherited errors of metabolism that happen as the result of the lack or malfunction of a particular enzyme needed to break down complex chemical compounds in the structures within cells known as lysosomes. In this case, the enzyme that is missing is acid ceramidase. The deficiency of this enzyme leads to the accumulation of a substance known as ceramide and is associated with characteristic symptoms and progressive tissue damage, particularly in the joints, liver, lung, and nervous system.
Farber's disease is usually recognized by the presence of three symptoms: painful and progressively deformed joints, nodules under the skin, and progressive hoarseness. Other organ systems may also be involved. Farber's disease is inherited as an autosomal recessive genetic trait.
Farber’s disease is usually fairly readily diagnosed because the typical features are so characteristic. Symptoms usually appear between the ages of two weeks and four months. They may include painful swelling of the joints, particularly the interphalangeal, metacarpal, ankle, wrist, knee, and elbow; nodules under the skin in relation to the affected joints and over pressure points; and a hoarse cry that may progress to inability to produce speech sounds (aphonia).
Other features may include poor weight gain, intermittent fever, and respiratory difficulties. The disease is progressive. Liver and spleen often are moderately enlarged, and there may be moderate swelling of the lymph nodes (lymphadenopathy). Nervous system involvement includes diminished muscle tone (hypotonia) and muscular atrophy, seizures, and impaired vision. Eye examination may show a diffuse grayish opaqueness (opacification) of the retina with a cherry red center. Intelligence may or may not be normal.
Farber’s disease is characterized by the body’s inability to produce lysosomal acid ceramidase, causing painful and progressive deformity of joints. The affected gene has been traced to a location on chromosome 8 (8p22-p21.3) and has been designated the ASAH gene. The inheritance pattern is autosomal recessive.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 8p22-p21.3” refers to a region on the short arm of chromosome 8 between bands 21.3 and 22. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Treatment for Farber's disease is symptomatic and supportive. Corticosteroid drugs may provide some relief for joint pain. Tracheostomy may be necessary if breathing passages become blocked due to nodular growths. Cosmetic surgery may be useful for removal of growths in the facial area. Genetic counseling will be of benefit for patients and their families. Prenatal diagnosis of FD is possible during the fifteenth to sixteenth weeks of pregnancy through the use of amniocentesis (testing of cells taken from the fluid in the water sac surrounding the fetus).
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Research continues on the metabolic defect that may cause symptoms of Farber’s disease. When this becomes better understood, scientists may be able to develop effective treatments.
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Levade T. Farber lipogranulomatosis. Orphanet. February 2005. 1pp.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Farber Lipogranulomatosis. Entry Number; 228000: Last Edit Date; 4/21/2005.