Lipogranulomatosis Farber (Farber lipogranulomatosis) - Gen ASAH1.
Farber lipogranulomatosis is the rare congenital disorder that affects lipid metabolism. In affected individuals, the lipids accumulate in cells and abnormally in tissues throughout the body, particularly around the joints. The classic features of the disease include a hoarse voice or a weak cry, lipogranulomas and swollen and painful joints. In addition, affected individuals may have difficulty breathing, hepatosplenomegaly and developmental delay.
They described seven types of lipogranulomatosis Farber according to their characteristics:
- Type 1, classic type is the most common form of the disease and is associated with the classic signs of voice, skin and joint problems starting a few months after birth. The developmental delay and lung disease also commonly occur. Generally, infants born with type 1 disease, survive only in early childhood.
- Types 2 and 3 have signs and symptoms usually less important than the other types. Affected individuals have the three classic symptoms and usually have no developmental delay. Children with this type of disease usually live until mid- to late childhood.
- Types 4 and 5 are associated with serious neurological problems. Type 4 generally cause health problems that threaten life in children due to massive lipid deposits in the liver tissue, spleen, lungs and immune system. In general, children with this type do not survive beyond their first year of life. Type 5 is characterized by the progressive decline of the function of the central nervous system, resulting in quadriplegia, seizures, loss of speech, myoclonus, and developmental delays.
- Types 6 and 7 are very rare, and affected individuals have other associated disorders.
This disease is due to mutations in the gene ASAH1, located on the short arm of chromosome 8 (8p22). This gene encodes an enzyme called ceramidase acid, which is located in lysosomes. The enzyme decomposes ceramides fat a fat called sphingosine and a fatty acid are recycled to create new ceramides for the body in use. Ceramides have several functions within cells. For example, they are a component of myelin that insulates and protects nerve cells.
They have identified at least 20 mutations in the gene ASAH1 causing disease. Mutations in the gene give rise to a marked reduction of acid ceramidase, generally below 10% of normal. As a result, the enzyme can not break correctly ceramides, accumulating in the lysosomes of various cells, including lung, liver, colon, skeletal muscle, cartilage and bone. Accumulating ceramide, along with reducing its degradation products of fatty acids, leading to the signs and symptoms of the disease. It is unclear whether the activity level of enzyme acid ceramidase is related to the severity of the disorder.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Farber lipogranulomatosis, by complete PCR amplification of exons ASAH1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).