Cystinosis is a rare, inherited metabolic disorder characterized by the accumulation of the amino acid cystine within the cells of the body. This accumulation is caused by a genetic mutation that impairs the transport of cystine out of the lysosomes, which are compartments within cells responsible for breaking down and recycling cellular waste.
There are three main forms of cystinosis, each classified based on the age of onset and severity of symptoms.
This is the most severe and common form of cystinosis, typically diagnosed in infancy. Babies with nephropathic cystinosis appear normal at birth but develop symptoms within the first year of life. The accumulation of cystine in various organs, especially the kidneys, causes damage to these organs, leading to kidney dysfunction and kidney failure if left untreated. Other symptoms may include growth retardation, excessive thirst and urination, poor appetite, vomiting, and kidney-related electrolyte imbalances.
This form of cystinosis presents in childhood or adolescence. While it is less severe than the nephropathic form, it still affects various organs, leading to symptoms such as kidney dysfunction, growth abnormalities, and vision problems.
This is the mildest form of cystinosis, primarily affecting the eyes. It may not cause significant kidney dysfunction, and individuals with this form may have relatively normal kidney function. The primary symptoms are ocular manifestations, such as photophobia (sensitivity to light), eye pain, and gradual deterioration of vision due to cystine crystals accumulating in the cornea.
Cystinosis is a progressive disorder, and if left untreated, it can lead to serious complications, including kidney failure, muscle wasting, and vision impairment.
Diagnosis of cystinosis involves clinical evaluation, laboratory tests to measure cystine levels in cells and tissues, and genetic testing to confirm the presence of mutations in the CTNS gene, which is responsible for the transport of cystine out of lysosomes.
Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder leading to end-stage renal disease and many extra-renal complications with crystal deposition in the conjunctiva and cornea being the most prominent but also in muscles, liver and many others organs.
First symptoms occur within the first year of life, usually presenting as renal Fanconi syndrome, a dysfunction of the proximal tubule that leads to polydipsia, polyuria, dehydration, proximal renal tubular acidosis, urinary loss of electrolytes, and growth retardation. In the urine, glucosuria and aminoaciduria can be found. In the case of glucosuria and normal serum glucose levels, one should always think of renal glucosuria or Fanconi syndrome. Glucosuria is the only parameter to be detected by urine dipstick in the Fanconi tubulopathy. The high protein turnover in the proximal tubule may explain why Fanconi syndrome is the first symptom of cystinosis.
Patients with the juvenile type of nephropathic cystinosis develop symptoms at an older age, often presenting with more unspecific symptoms than patients with infantile cystinosis like nephrotic syndrome or mild proximal tubulopathy, but not necessarily the complete picture of Fanconi syndrome. End-stage renal disease may occur. Most patients are diagnosed in the second decade of life, when onset of photophobia leads to ocular examination and cystine crystals in the cornea can be found.
Treatment for cystinosis aims to reduce the accumulation of cystine in the cells and manage its associated complications. The mainstay of treatment is cystine-depleting therapy, which involves the regular administration of cysteamine, a medication that helps remove excess cystine from the cells. The cysteamine prevent kidney damage and delay the onset of kidney failure, can also help improve growth and delay other complications related to cystinosis, such as muscle wasting and vision problems. This treatment can slow down the progression of the disease and improve outcomes, especially if started early in life. The treatment is generally started as early as possible, ideally shortly after the diagnosis, to optimize its benefits.
It is available in the form of capsules or a powder that can be mixed with food or liquid for easier administration, especially for children who may have difficulty swallowing capsules.
It is important to note that the treatment has to be continue throughout the whole person's life. Regular monitoring of cystine levels in the cells and overall kidney function is essential to adjust the dosage and ensure optimal management.
As with any medication, cysteamine may have potential side effects, and individual responses to the drug can vary. Common side effects may include gastrointestinal symptoms such as nausea, vomiting, and stomach pain. Regular follow-ups with a healthcare provider are crucial to assess treatment effectiveness, monitor side effects, and address any concerns or issues related to the medication.
Unfortunately, cysteamine is known for having a strong and distinct odor. The strong smell is primarily due to chemical composition of cysteamine, as it contains sulfur atoms, and sulfur compounds are notorious for pungent odors.
The strong odor can be bothersome to some patients and caregivers, especially when administering the medication to children or individuals sensitive to smells. However, it is essential to remember that the odor is not an indication of medication spoilage or inefficacy.
Other supportive measures, such as kidney function monitoring, kidney transplant (in severe cases of kidney failure), and management of related complications, are also part of the treatment. To mitigate the smell cysteamine can be taken with food or mixed with a small amount of applesauce or pudding to mask the taste and smell.
Cystinosis is a chronic condition that requires lifelong management and close medical supervision. With early diagnosis and appropriate treatment, individuals with cystinosis can lead relatively fulfilling lives and reduce the risk of severe complications associated with the disorder.
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Nephrol Dial Transplant 2014; 29: iv87-iv94