Cystinuria

The Cystinuria is a genetic metabolic disease in humans, in which there is an increased excretion of the amino acid cystine, as well as the structurally related amino acids arginine, lysine and ornithine in the urine. The disease is inherited as an autosomal recessive trait and is one next to the Hartnup syndrome and Glycinurie to the amino acid transport disorders. In the case of cystinuria the defect is in a homozygous or heterozygous for this mutation of rBAT gene on chromosome 2 (also SLC3A1, 2pter - q32.3 ) encoding the heavy subunit of the Cystintransporters ( molecular weight 90 kDa). Affected persons lacking this transmembrane transport protein in the epithelial cells of the small intestine and the proximal tubule cells, the cystine reabsorbed ( extracellular, oxidized form of cysteine ​​) and the amino acids mentioned above from the primary. Consecutively the separation, in particular cystine, to the 20 - to 30 -fold increase of the standard, while the concentration in the blood remains unchanged.

Epidemiology

The Cystinuria is a relatively rare disease with a prevalence of about 1:20,000. According to another source, the prevalence of all three subclasses ( type I to III) of classic cystinuria together 1:7000.

Clinic

Cystine has only one of the dibasic amino acids on a poor solubility in normal urine pH. From a concentration of ≥ 300 mg / l, there is a precipitation with to form hexagonal crystals in the urine or of cystine stones in the urinary tract ( about 1 % of all urinary stones ). 50 % of patients with cystinuria develop urinary stones, and of these 75 % show a bilateral occurrence. Symptoms of nephrolithiasis, urolithiasis, respectively, are colicky pain in the kidney bearing in stone passage, which may radiate to the groin. Haematuria may occur concomitantly, complicating a urinary tract infection can occur.

Diagnostics

Leading the way in cystinuria the characteristic amino acid pattern in the urine. The cyanide - nitroprusside test can be a qualitative determination of the amino acid cystine. A positive test indicates a concentration in the urine of more than 75 mg / l, and speaks for diagnosis. A negative test excludes the existence of cystinuria with high probability. Definitive clarity provides a molecular genetic analysis. In many cases the diagnosis is made ​​but only in the aftermath of the first manifestation of a stone suffering, because the disease is previously asymptomatic. For the diagnosis of urolithiasis include, besides the typical history and clinical findings, urinalysis, ultrasonography and urography.

Therapy

The acute therapy aimed to cater for smaller oligosymptomatischer stones on the trial of medical lysis with D- penicillamine or α - mercaptopropionylglycine with increased fluid intake, diuresis and Harnalkalisierung. Otherwise, comes, depending on the size of the stone, the entire urological or interventional - operative spectrum used (ESWL Extracorporeal shock wave lithotripsy =, PNL = percutaneous nephrolithotomy etc.). The actual therapy depends mainly on the prevention of chronic recurrent stone suffering, to avoid complications such as chronic urinary tract infections, renal failure, etc.. The basis for this is a consistently high fluid intake, to be achieved with a urine volume of ≥ 3 L / day. In order to avoid aggregation of the nocturnal cystine, should be supplied to the fluid and during the night. Since cystine is readily soluble in water at a pH of 7.5-8.0, a Harnalkalisierung with this target range, eg with sodium bicarbonate should be administered orally, sought. D-penicillamine and mercaptopropionylglycine - α may also be used in the prophylaxis, as better soluble form of cystine disulfides. Here, α - mercaptopropionylglycine to give due to the greater therapeutic margin of preference. A cystine- and methioninarme diet can be additionally useful.

Cystinuria in animals

In dogs the disease is known. Primarily occur urinary stones on that cause clinical symptoms, often in puppies at the age of 4 to 6 months. In kidney and bladder small to large stones and grit can form, leading to the closure of the organs. Without medical treatment ( surgery ) leads to kidney failure, bladder rupture and eventual death of the animal. Females are less affected than males, which can be explained by the short and longer urethra in males. The genetic defect leading to this cystinuria in some breeds of dogs, is now known, and by means of a DNA test of the genetic defect can be detected directly. This test not only already diseased animals, but also clinically healthy carriers can be identified that would spread this disease in the population further, and can not be detected by conventional laboratory tests. Previously known breeds in cystinuria are occurring increasingly Mastiff, Newfoundland and Irish Terrier.