Cystinosis (Cystinosis) - Gen TSSC
Cystinosis is a disorder caused by the accumulation of the amino acid cystine in the lysosomes of cells. The accumulation of cystine damages cells and often form crystals can accumulate and cause problems in many organs and tissues. Kidneys and eyes are particularly vulnerable to damage, but can also be affected muscles, thyroid, pancreas and testes.
There are three different types of cystinosis, in descending order of severity, are: nephropathic cystinosis, intermediate cystinosis and non - nephropathic or ocular cystinosis.
The nephropathic cystinosis begins in childhood, causing poor growth and a particular type of kidney damage (renal Fanconi syndrome) in which certain molecules to be reabsorbed into the bloodstream, are excreted in the urine. Kidney problems lead to loss of important minerals, fluids and many other nutrients. Loss of nutrients alters growth and may cause hypophosphatemic rickets, especially in the legs. Nutrient imbalances in the body lead to increased diuresis, thirst, dehydration and acidosis. At the age of 2 years, the cystine crystals may be present in the cornea. The accumulation of these crystals causes pain in the eye and photophobia. Untreated children develop complete renal failure in approximately 10 years. Other signs and symptoms that can occur in untreated, especially after adolescence people, including muscle deterioration, blindness, inability to swallow, diabetes, thyroid abnormalities, nervous system problems and infertility in affected males.
Signs and symptoms of cystinosis intermediate are the same as nephropathic cystinosis, but occurs at a later age because usually become apparent in adolescence. The kidney malfunction and corneal crystals are the main initial characteristics of this process. If left untreated, the intermediate cystinosis develop complete renal failure, but usually does not occur until late teens to mid-twenties.
People with non - nephropathic or ocular cystinosis often manifest photophobia, but usually do not develop kidney failure or other signs and symptoms of cystinosis. Due to the absence of severe symptoms, the age at which this form of cystinosis diagnosed is very variable.
The three types of cystinosis are due to mutations in the CTNS gene, located on the short arm of chromosome 17 (17p13), encoding the carrier protein cystinosin. Inside the cells, this protein is normally located outside the lysosomes, which are compartments in cells that digest and recycle molecules. When cystinosin is defective or absent, cystine accumulates and forms crystals in lysosomes. Accumulation damages the kidney and eye cells, but can also affect other organs.
There are more than 80 different mutations that can trigger cystinosis. The most frequent mutation is a deletion of a large part of the TSSC gene (sometimes referred to as deletion of 57 kb), which causes the complete loss of cystinosin. This deletion is responsible for approximately 50% of patients with cystinosis in people of European descent. Other mutations result encoding an abnormally short protein that can not perform its function of normal transport. Mutations that change small regions of the TSSC gene may allow the carrier protein keep part of its normal activity, resulting in a milder form of cystinosis.
This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell have mutations. The parents of an individual with an autosomal recessive disorder each has 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 cystinosis, by complete PCR amplification of the exons of the TSSC 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).