Cystinuria
Biochemical Cystinuria is the most common anomaly in the metabolism of the amino acid cystine, which is characterized by its appearance in the urine. Population studies have shown that its frequency is 1: 500, in 12.9% of children with different renal pathology develops secondary cystinuria.
The existence of cystine stones in the kidneys was known as early as the beginning of the nineteenth century, and in 1908 cystinuria was categorized as a congenital "error" in the metabolism. The first significant study of functional and biochemical changes on the part of the kidneys in cystinuria occurred in 1951. Subsequent studies have established that in the intestine there are similar disorders in the transport of amino acids.
Cystinuria is a hereditary autosomal recessive disease for which the existence of complete and incomplete recessive forms has been established. Parents heterozygous for a complete recessive gene do not show any clinical and biochemical abnormalities. In heterozygotes with an incomplete recessive gene, the excretion of amino acids of cystine and other amino acids through the kidneys is increased. These variations depend on the degree of occurrence of the mutant gene and determine the existence of several forms of cystinuria.
Data on the incidence of the disease are contradictory. According to different authors, the population frequency of the primary autosomal recessive cystinuria is from 1: 14,000 to 1: 40,000. Biochemical methods increase the excretion of cystine through the kidneys in 1 out of 250 Europeans, but here also include heterozygotes with an incomplete recessive gene. Homozygous cystinuria occurs at a frequency of 1: 20 LLC.Cystine kidney stones are found in about 2% of patients with kidney stone disease, more often in men, which is associated with anatomical features of the structure of the urinary tract.
The occurrence of cystinuria is associated with an increase in the concentration of cystine in the primary urine. In physiological conditions( normally), the cystine is filtered in the glomerular apparatus of the kidneys, and almost 90% of it is reabsorbed( reabsorbed) in the renal tubules due to the activity of the active transport system. The mutant gene in the homozygous state determines the inactivity of the transport systems, which leads to the cessation of the reabsorption of cystine. Cystine is poorly soluble in water: the saturation concentration of the cystine solution is not more than 400 mg per liter of liquid. Exceeding this threshold leads to the precipitation of cystine crystals into the sediment and the formation of stones( stones).
Currently, there are 3 genotypic variants of cystinuria that have differences in intestinal transport.
Type I - no transport of cystine in both the intestine and the kidneys.
Type II - reduced transport of cystine in the kidneys( 50%), complete absence of transport in the kidneys and intestines.
Type III - reduced transport of all amino acids in the kidneys with normal absorption in the intestine.
Clinically, cystinuria can manifest itself at almost any age, but more often it occurs at the age of 10-20 years. The main symptom of the disease is renal colic, which develops suddenly. Colic can be combined with obstruction( blockage) of the urinary tract and the attachment of a microbial-inflammatory process - pyelonephritis. At later stages of the disease, hypertension and chronic renal failure develop. Individual children have a lag in physical development due to a violation of back absorption and loss of essential amino acids by the body.
Cystinuria should be excluded in every case of kidney stone disease. As a screening, a special cyanide nitroprusside or iodine azide test is used, as well as a microscopic examination of urinary sediment to detect cystine crystals. With positive results, a quantitative determination of cystine in the urine is carried out.
Treatment of cystinuria primarily involves methods of diet therapy, which aims to restrict the intake of sulfur-containing proteins, intake of large amounts of liquid( 2 liters per day or more), the use of funds that alkalinize urine. A potato diet is offered, which, in addition to the potato prepared in various ways, includes vegetable soups, pies with jam, cabbage, cream and vegetable oils, fruits, sweets. The intake of methionine( a precursor of cystine) with food is limited in this case. However, a long restriction in the diet of methionine, an indispensable amino acid, is unacceptable for a growing organism, so this diet is prescribed for 3-4 weeks. Then, individuals with this disease receive normal nutrition, but with the inclusion of citrate mixtures, medications( diacarb, hypothiazide) at age dosages. The excretion of cystine from the body can be reduced by the appointment of glutamine and a diet with restriction of table salt. Penicillamine( dimethylcysteine) increases the solubility of cystine and is prescribed in a dose of 1-2 g per day. However, many respond to the introduction of the drug develop allergic reactions, arthralgia( joint pain) and even nephrotic syndrome. In order to avoid allergic reactions it is recommended to administer penicillamine inwards gradually, starting with low doses( 0.1-0.2 g per day), gradually increasing them. In recent years, less toxic penicillamine has been used to treat cystinuria. In cases of obstruction( obstruction) of the urinary tract, they resort to surgical treatment.
Medical genetic counseling of the family allows you to establish the degree of risk of re-birth of a sick child, an early targeted examination of which will allow you to assign the appropriate diet. The prognosis is generally favorable, if there is no infection and the development of chronic renal failure. It should be borne in mind the likelihood of repeated occurrence of cystine stones.
Persons suffering from the examined disease should be under constant medical supervision.