Cystinosis is a rare, inherited disease characterized by the abnormal accumulation of the amino acid cystine. The build-up of cystine in the cells eventually destroys all major organs of the body. Currently there is no cure, only a time demanding, around the clock treatment. This rare metabolic disease afflicts 75 children and young adults in Canada, and only 2,000 worldwide.

 

Cystinosis is a metabolic disease in which the amino acid cystine gets into the cells, but has no transporter out. Because of the defect in transportation, the cell crystallizes causing early cell death. Cystinosis slowly destroys the organs in the body including the kidneys, liver, eyes, muscles and the brain. With such a rare disease affecting such a small population, research money is scarce to nonexistent. And yet research on complicated diseases like cystinosis often lead to advancements in other rare diseases.

 

Cystinosis is an autosomal recessive genetic disease. This means that both parents are carriers of the abnormal gene that leads to this condition. The parents do not exhibit any of the symptoms of cystinosis. In such couples, the odds are that one-in-four of their children will have cystinosis. The gene for cystinosis, CTNS, was mapped to chromosome 17p13.

 

As proteins are degraded within the lysosomes of cells, the individual amino acids that make up the proteins are transported from the lysosome to the cell’s cytoplasm via specific transporters. The transporter for cystine is defective in children with cystinosis and this defect causes the cystine to crystallize within tissue. The cystine content of the cell is 50-100 times the normal value.

 

 

 

 

 

 

 

 

Diagnosis

As proteins are degraded within the lysosomes of cells, the individual amino acids that make up the proteins are transported from the lysosome to the cell’s cytoplasm via specific transporters. The transporter for cystine is defective in children with cystinosis, which causes the cystine to crystallize within tissues. This build up eventually destroys all the body’s organs including the kidneys, liver, muscles, white blood cells, eyes and central nervous system.

 

Cystinosis is a common cause of the Fanconi Syndrome, a renal tubular disease. By about one year of age, patients eliminate large volumes of urine and lose large amounts of salt and other minerals in their urine.

 

Without specific treatment, these children progress to end-stage renal failure by an average age of nine years. In the past, this meant death. Today these patients can receive renal dialysis or transplantation, but even with successful transplantations, they develop abnormalities in other organs.

 

Fortunately, the drug cysteamine slows the progression of cystinosis by removing the cystine from cells, but for the drug treatment to be effective, it must be taken every six hours. Although this has led to a much better future for these children, cysteamine is not a cure.

 

Cystinosis is an autosomal recessive genetic disease, which means that both parents are carriers of the abnormal gene that leads to this condition. In such couples, the odds are one in four that their children will have cystinosis.

 

Symptoms

There are three clinical forms of cystinosis: Infantile (nephropathic) cystinosis; late-onset cystinosis; and benign cystinosis. Infantile cystinosis is the most severe and the most common type of cystinosis. Children with nephropathic cystinosis appear normal at birth, but by 9-10 months of age have symptoms that include excessive thirst and urination and failure to thrive. Children often appear pale and thin and have short stature. The abnormally high loss of phosphorous in the urine leads to rickets.

After one year of age, cystine crystals appear in the cornea and cause a severe sensitivity to light (photophobia). Children with cystinosis also have an increased level of cystine in their white blood cells. In time, patients can develop problems such as hypothyroidism, severe muscle weakness and central nervous system complications. These children have normal intelligence, but have an unusual defect in short-term visual memory. Many have poor GI motility. Cystagon TM causes hyper secretion of gastric acid, resulting in gastric distress.

 

Effects of Cystinosis

Over a period of years, the cystine damages various organs inlcuding the kidneys, liver, muscles, white blood cells, eyes and central nervous system. The cystine crystallizes in celss throughout the body, slowly destroying the organs. The earliest abnormalities are seen in the kidney. Cystinosis is a common cause of the Fanconi syndrome, a renal tubular disease. By about one year of age, patients have very large volumes of urine and lose large amounts of salt and other minerals in their urine.

 

Without specific treatment, these children progress to end-stage renal failure by an average age of nine years. In the past, this meant death. Now these patients can receive renal dialysis or renal transplantation. However, even with successful renal transplantation, these children go on to develop abnormalities in other organs.

 

Fortunately, the drug cysteamine slows the progression of cystinosis by removing the cystine from the cells. In order for the drug treatment to be effective, it must be taken every six hours. Although this has led to a much better future for these children, cysteamine is not a cure.

 

 

 

 

 

 

 

Treatment

Cystinosis is a common cause of the Fanconi Syndrome, a renal tubular disease. Fanconi Syndrome is treated symptomatically. Fanconi Syndrome causes a loss of minerals and nutrients in the urine. Treatment requires free access to water and oral replacement of salts and minerals that are lost in the urine. High doses of vitamin D and phosphate are required to replace the lost nutrients and minerals and to prevent rickets.

 

The only specific treatment for cystinosis is cysteamine. Cysteamine is the only drug that slows the progression of cystinosis by removing the cystine from the cells. Cysteamine is a cystine depleting agent that helps to lower cystine levels in the cells. Cysteamine was designated an “orphan drug” as defined under the Orphan Drug Act of 1983. In 1992, Mylan Laboratories assumed responsibility for developing cysteamine in a capsule form. In 1994, the new product, called CystagonTM was available for use. Unfortunately CystagonTM has a very bad taste and smell and must be taken every six hours, every day.

 

Cysteamine eye drops help to dissolve cystine crystals on the cornea. In patients with severe photophobia, using these drops every hour while awake can remove the cystine crystals from the cornea. A pharmaceutical company is proposing these drops for FDA approval.

 

Although renal transplantation is usually required in patients with cystinosis who are diagnosed late and do not begin CystagonTM treatment at an early age, even patients who start CystagonTM at an early age may eventually require transplantation. This may be because patients find it impossible to continue taking CystagonTM four times a day at six hour intervals for their entire lives.

 

(Information from Cure Cystinosis International Registry - www.cystinosis.patientcrossroads.org)