Cystinosis is a rare metabolic disease affecting children. It is a genetic metabolic disorder causing excess of fluid (cystine) accumulation in vital organs including pancreas, liver, kidneys, muscles and even eyes. If not given early treatment, such children may develop kidney dysfunction at young ages. Under normal condition, amino acid and other fluids pass into the blood. But due to abnormality in metabolism, amino acid cystine gets collected in several body parts causing major complications.
Cystinosis is believed to be caused by wrong genetic mutation. Symptoms of cystinosis vary with the severity of fluid accumulation and the parts that are affected. Diagnosis can be made by urine culture and by measuring the cystine level secreted by the brain. Treatment involves only addressing the symptoms and nothing much can be done to control genetic mutation. Detecting the disease in early stage and prompt intervention can improve the symptoms. Kidneys and eyes are largely affected in people living with cystinosis.
Cystinosis Symptoms :
Symptoms of cystinosis are not the same for every person. The intensity of disease and the parts that are affected varies from one person to the other. And signs of cystinosis differ according to the organ affected.
- Nephropathic Cystinosis
It starts at the stage of infancy and this kind of cystinosis is severe. Kidney function is largely affected in the babies and passing urine becomes difficult. Kidney transplant is the only solution left in such cases. The symptoms of nephropathic cystinosis can be detected before the child completes one year. Normal development is lacking in such infants and they are deficient in height and weight like normal children of that age. Infants would have problems in feeding leading to lack of nutrition and weight loss.
They develop fanconi syndrome leading to kidney dysfunction. Babies would not have normal appetite and indulge in frequent vomiting. Some of the symptoms of nephropathic cystinosis include poor appetite, difficulty in feeding, excess of thirst, frequent urination and dehydration. Kidneys will not be able to reabsorb essential nutrients needed for the growth of body. If treated promptly there may be improvements in symptoms. Medications are prescribed to reduce the cystine levels in blood and to boost the function of kidneys. If not treated, it may gradually lead to kidney failure and death. Rate of survival is poor in such infants.
- Non Nephropathic Cystinosis
In this type, cornea of the eyes is affected causing vision problem. Symptoms unrelated to renal (kidneys) appear in these children. The symptoms vary according to the intensity of disease and age of the child. Several organs like liver, pancreas, intestine, spleen, brain and eyes are affected. The child may develop photophobia (high sensitivity to light) due to excess of deposits of cystine in the cornea. Corneal erosions are common in such children.
For some children, cystinosis can cause hypothyroidism (reduced thyroid hormone) or insufficient thyroid causing many complications like fatigue, dryness of skin, severe constipation and depression. Eyes may run out of tears and such children do not salivate or sweat like others. If left untreated, non nephropathic cystinosis can cause delay in puberty. In males, it can gradually cause hypogonadism, reduced production of testosterone. Children with cystinosis may have poor intelligence and often have learning disabilities in addition to vision problem. They may have psychological problems and some of them may have different facial features or abnormality in morphology.
Cystinosis Causes :
Cystinosis is a kind of lysosomal disorder. Lysosomes are essential part of cell that are actively involved in the process of digestion and removal of wastes. Lysosomes are enriched with special kinds of digestive enzymes that help in removing excess of food particles from the cell. Lysosomes are responsible for breaking down important nutrients like fats and carbohydrates and hence they are primary organ in the cell that carries digestive function.
When the lysosomes are not functioning normally, it leads to accumulation of cystine (leftover metabolic products) causing cystinosis. Cystine is present in the form of crystals in many types of cells gradually affecting many organs. Genetic mutation of CTNS gene can gradually cause cystinosis. CTNS genes are responsible for encoding cystinosin protein which is responsible for transporting cystine (a type of amino acid) from lysosomes. Due to lysosomal dysfunction cystine gets deposited in excess in various organs and tissues and forms crystals thus damaging several organs.
Cystinosis is a very rare disorder affecting one in 2 million people. Cystinosis is believed to the major cause of renal Fanconi syndrome causing renal failure in children.
- Since the symptoms are often confusing cystinosis is not detected easily and confused for other diseases.
- The doctor would observe for Fanconi syndrome and confirm his diagnosis with various testing procedure. This includes blood culture (for measuring amounts of cystine levels), urine culture (for identifying excess of minerals, amino acids and electrolytes) and various other tests. Renal function test is done based on the findings of blood test.
- If the eyes/vision is affected special magnification instrument is used by ophthalmologist to detect presence of cystine crystals in the cornea.
- Molecular genetic testing is done for confirming CTNS gene mutation.
- At present, cystine levels can be measured from the amniotic fluid of the womb to identify cystinosis even before birth.
Cystinosis Treatment :
Treatment is to be done based on the intensity of symptoms which differs in each child. Each child is to be treated on customized manner with teamwork of pediatricians, nephrologists and gastroenterologists. Kidney transplantation will be the last resort for treating cystinosis.
1 . Cystine Depletion
- FDA has approved drug by name Cystagon for cystinosis patients in 1994 and further Procysbi in 2013. Both act in helping extended release of cysteamine thus reducing cystine accumulation in the cells. This therapy indirect improves kidney function and reduces its damage significantly.
- Cystine depletion therapy should be started in early ages or once the diagnosis of cystinosis is confirmed. Probably your doctor would recommend such children to continue taking cysteamine throughout the life to prevent any kidney complications in future.
- For children affected with eyes due to cystinosis, cysteamine is given in the form of eye drops.
- Cysteamine therapy can cause adverse effects like vomiting, nauseated feeling and digestive problems.
2. Symptomatic Therapy
- For people with renal fanconi syndrome, it is recommended to take excess of fluids intake to prevent loss of fluids from the body. Supplemental ions containing sodium citrate and potassium are given to regulate the electrolyte balance of the body. ACE inhibitors are prescribed for some cases to slow down the kidney problem. Indomethacin is given to control loss of electrolytes in urine. In addition, the patients are given vitamin D and phosphates to prevent rickets.
- Health of affected children is closely monitored and proper nutritious diet is to be given. L-thyroxine and other growth hormone therapy are suggested for treating individuals with hypothyroidism.
- Suitable sunglasses are prescribed for children whose eyes are affected and they are asked to avoid bright light anywhere. Lubricating eye-drops are to be applied to prevent dryness of eyes. In case of corneal erosions, surgery is done for corneal transplant.
- For children with severe case of gastronomy problem surgical intervention is necessary for placing thin tubing in the stomach permanently for absorbing the nutrients.
Kidney Transplantation :
For more severe cases of kidney dysfunction and where other medications and therapy are not working, transplant is considered. Dialysis is done wherein supporting machine is attached to maintain the functions of kidney artificially. Transplantation is done for few cases depending on the progressive kidney dysfunction.