From Big Medical Encyclopedia

TsISTINURYYa (cystinuria; + Greek iiron wetting cystine) — the hereditary disease which is characterized by disturbance of transport of a number of amino acids (cystine, a lysine, arginine, ornithine) in epithelial cells of renal tubules and intestines and formation of tsistino-vy concrements in kidneys.

Existence of tsistinovy stones in kidneys was known at the beginning of 19 century. In 1908 A. E. Garrod called a cystinuria an inborn error of a metabolism. The first considerable research of functional and biochemical changes at C. Dent and sotr belongs., to-rye in 1954 established that in a basis patol. process increase in renal clearance of cystine and diaminomono-carboxylic amino acids lies. They stated a hypothesis of existence in kidneys uniform stereospetsifichesko-go the transport mechanism for cystine (see), a lysine (see), arginine (see) and ornithine, confirmed later nearby experimental and a wedge, researches. In 1965. Shooting gallery (S. The lake of Thier) with sotr. established that at C. similar disturbance of transport of amino acids is available in intestines.

The C given about frequency. are contradictory. At inhabitants of Europe the raised renal excretion of cystine is found by biochemical methods in 1 of 250 people, however this group included also heterozygotes with partial manifestation of a recessive gene; homozygous C. meets frequency of 1:20 000. In England, according to Robertson (W. G. Robertson, 1983), frequency homozygous C. makes 1:6000. Tsistinovy stones in kidneys are found approximately in 2% of patients with a nephrolithiasis (see), is more often at men in connection with anatomic features of a structure of their urinary tract.

Etiology and pathogeny. The cystinuria is inherited on autosomes - but - recessively to type. There are full and incomplete recessive forms of a disease. At parents, heterozygous on completely recessive gene, a wedge, and biochemical symptoms of a disease are not found, at the heterozygotes having not completely recessive gene increase in renal excretion of cystine and diaminomonocarboxylic amino acids is noted, however it remains to lower, than at homozygotes. Existence of several phenotypical forms C. is defined, apparently, by a multiple allelism (see. And llet).

Development of C. it is connected with strengthening of cystine in primary urine whereas increase in contents in it has no diaminomonocarboxylic amino acids of pathogenetic value. In fiziol. conditions cystine is filtered in the glomerular device of kidneys and nearly 90 its % re-are absorbed in renal tubules thanks to activity of active transport system. At the same time its renal clearance (see) does not exceed 2 ml! min. The mutant gene in a homozygous state causes inaction of membrane transport systems, as a result of it the reabsorption of cystine and (or) diaminomonocarboxylic acids stops. At the same time the clearance of cystine can be equal to clearance of inulin — a standard of glomerular renal filtering (on average 127 ml! mines) or to exceed it. We will badly dissolve cystine in water (concentration of saturated solution of cystine at pH equal 7,0, makes no more than 400 mg/l). Exceeding of this threshold leads to loss of crystals of cystine in a deposit and to formation of concrements. Removal of cystine with urine at patients reaches 250 mg on 1 g of creatinine a day and more (it is normal of 75 — 125 mg on 1 g of creatinine a day). At the studying of transport of cystine and diaminomonocarboxylic amino acids in kidneys which became possible thanks to development by Formen (J. W. Foreman, 1981) and sotr. technology of allocation of the isolated membranes of proximal renal tubules and receiving membrane vesicles, existence of two transport systems (I and II) for cystine and two (II and III) — for diaminomonocarboxylic amino acids was installed. It turned out that and the diaminomonokarbono-Vyya amino acids have cystine both independent, and one general (II) transport system. Separate transport systems are located in basolateral (side) membranes of tubules, the general — in lyuminalny (turned into a gleam of a tubule). At classical C. the general transport system of a lyuminalny membrane suffers, than increase in renal excretion of all four amino acids speaks. However owing to genovariation it can be switched off only transport system, specific to cystine, that is shown isolated by C. Separate transport systems of cystine (I) and diaminomonocarboxylic acids (III) provide generally metabolic requirements of the cell. At defect of the general (II) transport system the cystine accumulated in a cell comes out in a gleam of tubules, creating visibility of canalicular secretion of cystine, at the same time its clearance exceeds the size of glomerular renal filtering.

In a crust, time allocate three genotypic options C., differing on extent of disturbance of absorption in intestines and size of excretion with urine of cystine and diaminomonocarboxylic to - t: The I type is characterized by lack of transport of cystine and diaminomonocarboxylic amino acids in intestines and kidneys,

the II type — decrease (to 50%) transport of cystine in kidneys and total absence of transport of diaminomonocarboxylic amino acids in kidneys and intestines, the III type — decrease in transport of all listed amino acids in kidneys at their normal absorption in intestines. At heterozygotes of the I type renal excretion of cystine normal, at heterozygotes

II and III types increase in excretion of cystine and other diaminomonocarboxylic amino acids is noted. Existence of various types C. connect with allelic mutations of one gene.

Pathoanatomical r t and the N and is characterized by hl. in the way inflammatory changes of kidneys as intersticial nephrite (see), pyelonephritis (see), a nephrolithiasis (see).

The clinical picture of a cystinuria can be shown at any age, a thicket in 10 — 20 years. The main symptoms of a disease are renal colic, disturbances of urodynamic owing to obstruction of urinary tract and pyelonephritis. Later arterial hypertension (see arterial hypertension), a chronic renal failure develops (see). Certain children have a lag in physical development that is caused by loss by an organism of irreplaceable amino acids.

Diagnosis. In each case of a nephrolithiasis at the child it is necessary to exclude a cystinuria. At the same time use cyanide-nitro-prussiate or iodine-azidny tests, and also microscopic examination of an uric deposit for the purpose of detection of crystals of cystine. At positive takes quantitative definition of cystine in urine by methods of a thin-layer chromatography (see), a high-voltage electrophoresis is carried out (see) or by means of a chromatography on ion-exchange resins.

Treatment consists in purpose of a large amount of liquid (2 l a day and more), diets with restriction of sulfur-containing proteins and inclusion of the products alkalizing urine. For this purpose use a potato diet, edges to a dress e potatoes made in the different ways includes vegetable soups, jam and cabbage pies, creamy and vegetable oils, fruit, sweets. The amount of methionine (the predecessor of the cystine) arriving with food (cottage cheese, cheeses, lactic products, meat, fish, eggs, bean), at the same time is limited to 0,7 g a day. However because long restriction of this irreplaceable amino acid is not indifferent for the growing organism, such diet is appointed no more than to

3 — 4 weeks then patients receive usual food, but with an exception of cottage cheese, fish, eggs. Appoint hydrosodium carbonate, citrate mixes, Diacarbum, hypothiazid. Renal excretion of cystine manages to be lowered by means of a glutamine and a diet with restriction of sodium chloride. For the purpose of solubilization of cystine apply Penicillaminum (dimethylcysteine) on 1 — 2 g a day. Because at many patients at administration of drug allergic reactions, arthralgias, in nek-ry cases a nephrotic syndrome, etc. develop, treatment is recommended to be begun with small doses (0,1 — 0,2 g a day), gradually increasing amount of the administered drug. In connection with the introduction of Penicillaminum in chemical reaction with pi-ridoksal-5-phosphate and an inactivation of the last it is necessary to appoint in addition piridoksinony in recent years use less toxic N........................ At emergence of obstruction of urinary tract resort to an operative measure.

The forecast, as a rule, favorable, worsens at emergence of a renal failure.

Prevention consists in medicogenetic consultation of a family (see. Medicogenetic consultation) and establishment of a risk degree of the repeated birth of the sick child. For the purpose of detection of a disease in a preclinical stage conduct mass examinations of the children's contingents. For the prevention of a nephrolithiasis and hron. the renal failure needs the early purposeful inspection of the child allowing to reveal a condition of homozygosity on a gene of a cystinuria and purpose of a diet. Due to a possibility of recuring of tsistinovy stones patients shall be under constant dispensary observation.

Bibliography: Ignatova M. S. and Vel-tishchev Yu „E. Children's nephrology, page 302, L., 1982; ForemanJ.W.,

McNamara P. D. a. Segal S. Renal transport of cystine by isolated renal tubu-ies and brush-border membrane vesicles, in book: Transport and inherited disease, ed. by N. R. Belton a. C. Toothill, p. 263, Lancaster a. o., 1981; Thier S. O. a.,

S e g a 1 S. Cystinuria, in book: Metabolic basis of inherited disease, ed. by J. B. Stan-bury a. o., p. 1578, N. Y. a. o., 1978.

BB. E. Veltishchev.