The Invitae Cystinosis Test analyzes the CTNS gene; which is associated with cystinosis, or the accumulation of crystals from the amino acid cystine within multiple tissues of the body. This test is useful for the diagnosis of patients in whom cystinosis is suspected due to clinical symptoms or biochemical findings. Identification of disease-causing variants provides accurate risk assessment and carrier status of at-risk relatives.
Cystinosis is a lysosomal storage disorder caused by the inability to pump the amino acid cystine out of the lysosome. This leads progressive cystine accumulation, the formation of cystine crystals and cellular damage. There are three commonly recognized clinical types defined by age of onset and clinical presentation: nephropathic cystinosis, intermediate cystinosis, and non-nephropathic or ocular cystinosis.. The most common type, nephropathic cystinosis, typically presents around age 6 months with renal Fanconi syndrome. Clinical and laboratory findings typically include failure to thrive, vomiting, constipation, dehydration, polyuria, polydipsia, rickets, hypokalemia, metabolic acidosis, hypophosphatemia, hypocalcemia, and increased urinary excretion of electrolytes, minerals, glucose and amino acids. Without treatment using cystine depletion therapy, affected individuals progress to end-stage renal disease in childhood. Additionally, affected individuals typically develop cystine crystals in the cornea by 16 months of age. This later leads to photophobia and other ocular abnormalities by mid-childhood or adolescence. Additional complications can develop over time including hypothyroidism, primary hypogonadism in males, delayed puberty, impaired sweating, pancreatic insufficiency, hypopigmentation, coarsening of facial features, and myopathy. Intelligence is typically normal, however some individuals may have mild neurocognitive abnormalities such as deficits in visual spatial and visual memory skills, and mild motor deficits.
Treatment is available for cystinosis via cystine depletion therapies. Cysteamine bitartrate can prevent or delay onset of some of the systemic complications of cystinosis while cysteamine ophthalmic solution is used for the ocular manifestations. Renal transplant may be necessary for those with advanced renal disease. Life expectancy is variable and based on management, however for individuals treated early with cystine depletion therapy survival into the 6th decade of life or later is possible.
An estimated 5% of affected individuals have intermediate cystinosis, characterized by onset of symptoms in childhood or adolescence. Individuals with intermediate cystinosis typically have a milder form of renal Fanconi syndrome and slower progression of disease compared to those with infantile onset of symptoms. In rare cases adults can present with non-nephropathic cystinosis, which is characterized by isolated corneal cystine crystals and photophobia.
100% of patients with a clinical diagnosis of cystinosis are expected to have biallelic pathogenic variants in the CTNS gene.
Cystinosis is inherited in an autosomal recessive manner.
The incidence of cystinosis is estimated to be around 1 in 100,000 to 200,000. The incidence may be higher in certain populations, such as in Brittany, France, which has an estimated incidence of 1 in 26,000, and Saguenay-Lac-St-Jean, Canada, which has an estimated incidence of 1:62,500 live births.
For considerations for testing please refer to:
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|