Cystinosis is a rare, degenerative, inherited disease in which the amino acid, cystine, accumulates abnormally in all cells of the body due to a defective mechanism to transport it out of the cells. This in turn leads to early cell death. Cystinosis therefore slowly destroys all the organs of the body; the kidneys, liver, eyes, muscles, pancreas, thyroid and the brain.
There are three clinical forms of Cystinosis:
Infantile nephropathic Cystinosis is the most common and severe form of Cystinosis. Symptoms begin in infancy, often before one year old and include failure to thrive, height retardation, rickets, vomiting, loss of appetite, constipation, photophobia (sensitivity to light).
The earliest abnormalities are seen in the kidney and are known as Fanconi Syndrome. Symptoms of Fanconi Syndrome include excessive thirst and excessive urination. Minerals and nutrients are lost in the urine and results in several problems such as rickets which occurs when low levels of phosphate and vitamin D are present.
Late-onset nephropathic Cystinosis is not usually diagnosed before the age of 12 and the disease progresses slowly. Cystine crystals are present in the cornea and conjunctiva of the eye and in the bone marrow. Kidney function is impaired and individuals with this form of Cystinosis may also develop Fanconi Syndrome.
Adult (benign or non-nephropathic) Cystinosis begins in adulthood and does not result in any kidney impairment. Cystine crystals accumulate in the cornea and conjunctiva of the eye and photophobia is present.
As the disease progresses other complications can include muscle wasting, swallowing difficulties, breathing difficulties, diabetes, hypothyroidism, late puberty, dementia, blindness.
How is Cystinosis Inherited?
Each person carries more than 30,000 genes, among which there is an estimated defect in approximately seven of them. Cystinosis is known as a recessive genetic disease because parents do not exhibit symptoms but they each carry the same genetic defect for Cystinosis.
Each time two carriers of this gene of have a child together there is a 25% risk of having a child with Cystinosis. The risk is the same for both boys and girls and unaffected siblings of a child with Cystinosis have a 66% risk of being a carrier of the gene.
The incidence of Cystinosis is estimated to be 1 case per 100,000 – 200,000 live births.
How is Cystinosis Diagnosed?
- Cystinosis can be confirmed by measuring the level of cystine in the white blood cells which is always elevated in a positive diagnosis.
- An ophthalmologist will make a slit lamp examination of the eyes to check for the presence of crystal deposits on the cornea.
- Prenatal diagnosis is available for families known to be at risk for having a child with Cystinosis. Chorionic villus sampling is performed at 8-9 weeks of gestation and amniocentesis is performed at 14-16 weeks of gestation.
Treatment of Cystinosis
There is a specific treatment for Cystinosis but there is not a cure. The drug cysteamine bitartrate, known as Cystagon™, helps reduce cystine accumulation within the cells and has proven effective in delaying renal failure and improving growth. It is not yet known whether this benefits all organs of the body as some complications of the disease appear much later than others.
Cysteamine treatment is only effective if taken every six hours, day and night for life. It does however have some very unpleasant side effects including nausea, vomiting, abdominal pain, body and breath odour. There are also some very rare and extremely serious side effects which can cause changes in bones and skin tissue. Any unusual
clinical occurrences must be discussed with the patient's physician.
There is also a slow release formulation of this drug, known as Procysbi™ which is only taken twice a day, every twelve hours. However this is not yet available in Ireland.
Eyedrops to remove corneal crystals, Cystadrops™, are given four times a day, every day.
- Due to impaired kidney function children and adolescents need to take mineral supplements such as calcium, potassium, vitamin D, phosphate and sodium bicarbonate to replace those lost.
- As the kidneys are the first organ to be severely affected, kidney function slowly diminishes and a transplant may be needed. The transplanted kidney is not affected by Cystinosis.
- Some children with particularly poor growth may receive growth hormone treatments.
- Some children may have difficulty swallowing, may vomit a lot and experience abdominal pain. They will be evaluated by a gastroenterologist and may require additional treatments or medications to help alleviate their symptoms.