Cystinosis

Cystinosis is a rare disease characterized by the accumulation of cystine in various tissues (kidneys, retina, thyroid), which leads to its progressive deterioration. Cystine is a dimer made up of two units of cysteine, one of the amino acids that are part of many proteins. Its incidence is low, since it affects one in every 100,000-200,000 newborns each year.

It is an autosomal recessive genetic disease, that is, it requires both genes to be altered for symptoms of the disease to manifest. The affected gene is called CTNS, which is located on the short arm of chromosome 17. More than 100 mutations of this gene associated with the disease have been described.

This gene encodes the protein cystinosine, which is responsible for transporting cystine through the membranes of lysosomes, cellular organelles that contain enzymes responsible for digesting external and internal substances. When cystinosine fails, cystine accumulates in lysosomes, causing progressive deterioration of the affected organs. Cystine crystals are formed in practically all the tissues of the body, the kidneys being the most affected organs.

Types of cystinosis

Infantile cystinosis It is the most frequent of all, it accounts for 95% of cases, and also the most serious. It presents at 3-6 months of life as what is known as in which there is an excessive elimination in the urine of several substances, such as glucose, phosphates, bicarbonates, sodium, potassium, carnitine and amino acids (especially cysteine) .

Loss of these substances leads to increased urine production (polyuria), metabolic acidosis, growth retardation, and rickets resistant to vitamin D treatment. The onset of the disease may be delayed up to 12-18 months and kidney function begins to be affected from the age of six. Without treatment, this leads to chronic kidney failure that becomes terminal around 10 years of age. The first manifestation is excess urine production, which can lead to dehydration episodes, especially when they coincide with other febrile symptoms.

The loss of phosphates and bicarbonates supposes growth retardation, so that by one year of age the patients have fallen from a normal initial percentile in both weight and height to being below the 3 percentile. In general, the mean height is around 143 cm in men and 129 cm in women. Photophobia usually appears at 3-4 years of age, as well as eyelid spasms, progressive retinal depigmentation, decreased color vision from the age of 10 and visual acuity deficits.

Caused by cellular lesions secondary to the accumulation of cystine in the thyroid, it can develop from the age of 10. Other possible alterations are delayed puberty, muscle atrophy, swallowing difficulties, aphonia, diabetes, liver involvement, seizures, visual perception disturbances, memory deficit, skin hypopigmentation or premature aging of the skin.

Juvenile cystinosis It is very rare, appears between 12 and 17 years of age and kidney failure is delayed until the third decade of life.

Cystinosis of the adult It is very unusual and differs from the previous ones in that there is no kidney involvement, which is why it is usually called benign, ocular or non-nephropathic cystinosis, because it essentially causes ocular symptoms such as photophobia and lacrimation caused by the accumulation of cystine crystals in the cornea.

Diagnosis of cystinosis

The diagnosis is initially clinical, carried out by the pediatrician, taking into account the family history of this disease. At an analytical level, the cystine accumulated in white blood cells is determined, which in these patients is very high, above ten times the normal value. Prenatal diagnosis can be made by chorion biopsy or through fetal DNA studies. This diagnosis is recommended if there is a family history of this disease.

Treatment

Treatment should be symptomatic and specific and should be started as soon as possible to delay the progressive deterioration of kidney function as long as possible. Symptomatic treatment will be based on correcting ion disorders, improving nutritional deficits and providing phosphates and vitamin D to prevent rickets. In some cases, improvement has been seen with the use of growth hormone, especially if it is used early.

Today we have cysteamine, which is the drug of choice for the treatment of cystinosis. This drug allows the release of cystine from the lysosomes, which does not accumulate in the tissues and does not have its harmful cellular effect. The use of cysteamine delays the deterioration of renal function, improves growth, reduces ocular damage when used in eye drops or eye gel, and significantly reduces the appearance of hypothyroidism.

Despite everything, kidney function continues to deteriorate, which is why these patients end up requiring a kidney transplant, although luckily now at more advanced ages, towards the third decade of life. Transplantation supposes a significant improvement in the quality of life of patients and it has been seen that, in general, kidney damage is not reproduced in transplanted organs.

It is important to go to the pediatrician's controls to detect this disease early and if there is a family history, consider prenatal diagnosis if you want to have offspring.

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• Genetic disease that consists of the accumulation of cystine in various tissues (kidneys, retina, thyroid), which leads to its progressive deterioration.
• There are three forms of cystinosis, the most common childhood of all, 95% of cases, and also the most serious. The others are the juvenile and the adult.
• It is important to go to the pediatrician's controls to detect it early and, if there is a family history, consider prenatal diagnosis if you want to have offspring.