Cystinosis
The disease is inherited by an autosomal recessive type. The nature of the gene mutation is not established. Currently, the following forms of cystinosis are distinguished.
1. Heavy children's uniform. Children are born phenotypically healthy, but in the first months of life they have polyuria( more urine output than normal), dehydration( loss of large amounts of fluid), persistent or recurring fever. Then growth slows down and signs of rickets appear. However, they can not be treated with vitamin D. There is photophobia, on the retina of the eye, the areas of absence of the pigment are combined with point pigmented clusters. An early sign is the evenly distributed areas of corneal opacity, in the blood cells, even without coloration, cystine crystals are found. The further course is characterized by a sharp lag in the growth and development of the child and the rapid development of renal failure with acidosis( a shift in the acid-base balance of the body to the acidic side), edema, anemia. Children die in cases of uremia( the appearance of urine components in the blood), not reaching 10 years of age. Diathesis is a predisposition to the development of nephropathy.
2 .The juvenile form of cystinosis is manifested later, the growth of children slows down, the retinal damage, photophobia are also detected. Crystals of cystine are found in blood cells, bone marrow cells, cornea and conjunctiva. The pathology of the kidneys develops slowly at the age of 10-12 years. There is no appearance of amino acids in the urine, Fanconi syndrome does not develop. Chronic kidney failure is formed in adolescence.
3. The benign form of cystinosis ( adult type) is known, which is not clinically apparent, although cystine crystals can be found in blood cells and cornea.
Detailed description deserves an early pediatric form of cystinosis. An early biochemical indication is the appearance of glucose in the urine( from traces to a fairly large number).Also characteristic feature of this disease is the appearance in the urine of a significant number of amino acids. Excretion in the urine of cystine is increased to the same extent as the excretion of other amino acids increases. Cystine stones in the kidneys are rare. The excretion of phosphate in the urine is combined with a violation of absorption of inorganic phosphates in the intestine. Almost always there is a protein in the urine. Despite the metabolic acidosis( shifting the pH to the acid side) in the blood, the urine reaction remains alkaline. In this case, significant amounts of ammonium ions are emitted. With damage to the glomerular apparatus of the kidneys, erythrocytes appear in the urine. A decrease in the content of phosphates and potassium in the blood serum is detected. The residual nitrogen and urea of blood in the early stages are not changed.
The concentration of cystine in cells exceeds the normal values by 100 times. In blood plasma, it does not reach the maximum permissible threshold. Intracellular deposition of cystine with cystinosis occurs with the completely normal activity of the enzymes that effect its degradation and oxidation. Almost 80% of intracellular cystine is included in special cell granules, so it is inaccessible to enzymes that split it. In the cells of parents of children with this disease, the content of cystine is 6 times higher than normal. It significantly increases in the cells of amniotic fluid during pregnancy with a homozygous fetus, which can be used as a diagnosis of the pathology in question even before the birth of the child.
Treatment. The use of penicillamine( dimethylcysteine, cysteamine) preparations is suggested. The kidney transplantation is applied, thus the expressed cystinosis in the transplanted kidneys does not develop. A non-cystine diet is proposed, as well as protein replacement in nutrition with a mixture of amino acids( without cystine).The effectiveness of treatment "synthetic diet" could not be proved.