Gen SPTLC1 - hereditary sensory neuropathy IA (Hereditary sensory neuropathy type IA) type
Hereditary sensory neuropathy Type IA is a condition characterized by peripheral neuropathy. Many affected people have paresthesia, numbness, and a decreased ability to feel pain and distinguish between hot and cold. Some affected individuals do not lose the feeling, but instead feel sharp pains in the legs and feet. As the disease progresses, sensory disturbances can affect the hands, arms, shoulders, joints and abdomen. Affected individuals may also develop muscle weakness and atrophy as they age. As the disease progresses, some affected individuals require a wheelchair.
People with hereditary sensory neuropathy usually develop type IA and foot ulcers and infections of the soft tissues of the fingers that are slow to heal. Because affected individuals may not feel the pain of these injuries sometimes they do not seek immediate treatment. If left untreated, ulcers can become infected and even require amputation of the limb or its surroundings. Some people have sensorineural hearing loss usually in late adulthood.
Signs and symptoms of sensory hereditary neuropathy type IA may begin at any time between adolescence and adulthood late. While the characteristics of this disease tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are treated properly.
Hereditary sensory neuropathy Type IA is due to mutations in the gene SPTLC1 (serine palmitoyltransferase long chain based subunit 1), located on the long arm of chromosome 9 (9q22.2), encoding a subunit of the enzyme serine palmitoyltransferase (SPT) . The SPT enzyme is involved in obtaining sphingolipids. Sphingolipids are important components of cell membranes that play a role in many cellular functions. The SPT enzyme initiates the first stage of production of sphingolipids, in which the molecules of serine and palmitoyl CoA join to form a molecule called cetodihidrosfingosina (ketodihydrosphingosine). Certain additional chemical reactions convert cetodihidrosfingosina in various types of sphingolipids. Inside the cell, the PTS enzyme found primarily in the endoplasmic reticulum.
They described at least nine mutations in the gene responsible for hereditary SPTLC1 sensory neuropathy type IA. These mutations consist of amino acid changes in the SPTLC1 subunit. A particular mutation has been identified in multiple families affected worldwide replaces the amino acid cysteine with the amino acid tryptophan at position 133 in the SPTLC1 subunit (Cys133Trp or C133W). Gene mutations SPTLC1 SPTLC1 reduce the amount of functional subunit is synthesized, which results in an enzyme with altered activity SPT. This altered enzyme makes molecules called deoxiesfingoides bases, do not occur. As a result, the production of the enzyme SPT sphingolipid is reduced. Overall, there appears to be a decrease in production of sphingolipids because the body can compensate for the reduced production of the enzyme SPT. Accumulation deoxiesfingoides bases is toxic to neurons. The progressive destruction of neurons caused by the accumulation of toxic molecules resulting in a loss of sensation and muscle weakness.
Hereditary sensory neuropathy Type IA is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with hereditary sensory neuropathy Type IA by complete PCR amplification of exons SPTLC1 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).