This is an inherited condition causing the accumulation of amino acid cysteine within the cells. An excessive amount of crystals can accumulate and cause damage to the cells affecting several parts of the body particularly the kidney and the eyes. Cystinosis is generally characterized into three forms; nephropathic cystinosis, intermediate cystinosis and non-nephropathic cystinosis. The nephropathic cystinosis is the most common and a severe form that occurs in infancy. It can cause poor growth and kidney damage (renal Fanconi syndrome) where certain substances that should be reabsorbed into the bloodstream are instead excreted in the urine. These children require early detection and the initiation of treatment can help slow the progression of the symptoms. Children who are untreated can experience complete kidney failure by the age of 10.
Causes
Nephropathic cystinosis develops because of a genetic mutation identified in the gene CTNS. This genetic mutation can cause the deficiency of a protein called cystinosin. Within the cellular structure, the lysosomes are present which are responsible for the digestion and recycling of materials. The protein cystinosin helps move the cysteine out of the lysosomes. The genetic mutation can cause the defective or absent cystinosin and as the result, cysteine can accumulate forming crystals in the lysosomes. This accumulation can damage the cells of several organs of the body such as the kidneys and the eyes. Nephropathic cystinosis is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective.
Symptoms
The symptoms can become evident after 6 months of the infant’s life. The initial symptoms are the growth failure and renal Fanconi syndrome that are the complications of the condition. They may also present episodes of vomiting, poor appetite and feeding difficulties that contribute to their failure to gain weight and grow at the expected rate. Fanconi syndrome is a rare condition characterized by the kidney dysfunction that becomes apparent by the age of 6 and 12 months of age. The kidney tubules are not effectively functioning by failing to reabsorb certain essential chemicals in the body such as potassium, calcium, phosphate, certain proteins and electrolytes. As the result, they often have an abnormally low level of these substances in the body. Additional symptoms of Fanconi syndrome include excessive production and passage of urine, excessive thirst, vomiting and dehydration. The affected children also have the progressive softening and weakening of bones (rickets) because of the kidney’s inability to reabsorb phosphorus.
Diagnosis
The diagnosis is based on the identification of characteristic symptoms, a thorough clinical evaluation and with various diagnostic tests. The cystine level can be measured in the white blood cells which can diagnose the cystinosis. The urinary examination can show the excessive loss of various nutrients that can indicate the renal Fanconi syndrome. A molecular genetic test can also help confirm the diagnosis by detecting the mutation responsible for causing this condition.
Treatment
The cysteine depleting therapy can lower the cysteine levels within the cells. This can slow the development and the progression of kidney damage. Also, this therapy can help delay the need for a kidney transplant. The renal Falconi syndrome is treated by including a high intake of fluids to prevent dehydration. Sodium bicarbonate, magnesium and potassium can also help regulate the normal balance of electrolyte. Phosphates and vitamin D can help with the prevention of rickets.
References
https://rarediseases.org/rare-diseases/cystinosis/
https://rarediseases.info.nih.gov/diseases/9755/nephropathic-cystinosis
https://ghr.nlm.nih.gov/condition/cystinosis#inheritance
