Cystinosis is a rare inherited, lysosomal storage disorder caused by a defect in the CTNS gene. The CTNS gene is responsible for providing the instruction code for the production of an essential protein called cystinosin, which is essential for transporting the amino acid, cystine, out of lysosomes. When cystinosin is deficient, cystine accumulates and forms crystals. The build-up of cystine crystals in lysosomes leads to tissue and organ damage causing the progressive symptoms of cystinosis.1
Like other lysosomal storage diseases, patients with cystinosis have a wide range of symptoms depending on the age of onset and degree of severity. The diagnosis of cystinosis is often delayed due to the rarity of the disease and the varied and often times, incomplete set of symptoms.
Nephropathic-infantile cystinosis is the most common and severe form of cystinosis. The kidneys and eyes are most vulnerable to the accumulation of cystine crystals. Infants with the disorder are extremely fussy babies and initially show failure to thrive and later failure to grow normally. By 6 months of age, infants experience clinical symptoms of renal Fanconi syndrome (kidneys are unable to conserve water and essential salts and proteins). Symptoms include excessive thirst, dehydration, frequent urination and vomiting. Infants also develop secondary complications due to their kidney problems, including loss of vitamin D and calcium, leading to rickets and seizures. As the disease progresses, cystine crystals deposit in the cornea of the eye causing significant pain and sensitivity to light (photophobia).2
Juvenile or late-onset nephropathic cystinosis is generally diagnosed in childhood or adolescence. Signs and symptoms are similar to infantile-nephropathic cystinosis including renal disease and muscle weakness and atrophy.3
There is also a non-nephropathic form of cystinosis that involves the cornea of the eye, causing photophobia, and is typically diagnosed in adulthood.4
Cystinosis is a rare, lysosomal storage disorder with an estimated incidence of 1 in 100,000 to 200,000 live births.5 In the United States, approximately 500 children and young adults are affected and roughly 2,000 individuals worldwide are affected.6 There is an increased frequency of cystinosis in Brittany, France noted at 1 in 26,000 due to the local population being descended from a common ancestor (founder effect).4
How is Cystinosis Inherited?
Cystinosis is inherited in an autosomal recessive manner. Normally, a person has two working copies of the gene that provides the instruction code for making the CTNS transport protein. When a person has one normal gene and one faulty gene they are a “carrier” for cystinosis and do not develop the disease. When two carriers have children, each parent will pass one of their genes (either the normal gene or the faulty gene) to their child. With each pregnancy, two carrier parents have a 25% chance of having an unaffected child, a 1 in 2 (50%) chance of having a carrier child, and a 1 in 4 chance (25%) of having a child affected by cystinosis.7 Males and females are equally affected.
How Common is Cystinosis?
Cystinosis is a rare, lysosomal storage disorder with an estimated incidence of 1 in 100,000 to 200,000 live births in the general population.5 In the United States, approximately 500 children and young adults are affected and roughly 2,000 individuals worldwide are affected.6 There is an increased frequency of cystinosis in Brittany, France (1 in 26,000) due to the local population descending from a common ancestor (founder effect).4
1 Wilmer MJ et al. Cystinosis: practical tools for diagnosis and treatment.
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3 Nesterova G et al. Cystinosis: the evolution of a treatable disease.
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4 Gahl WA et al. Cystinosis.
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5 Nesterova G et al. Cystinosis.
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6 Cystinosis Research Foundation https://www.cystinosisresearch.org/about-cystinosis/diagnosis. Accessed August 8, 2017.
7 National Organization for Rare Diseases (NORD). www.rarediseases.org/cystinosis.