Cystinuria
| Classification according to ICD-10 | |
|---|---|
| E72.0 | Disorders of the amino acid transport cystinuria |
| ICD-10 online (WHO version 2019) | |
The Cystinuria is a genetic congenital metabolic disorder , which is an increased excretion of the amino acid cystine , as well as the structurally related amino acids arginine , lysine and ornithine is via the urine. The disease is autosomal - recessive inherited, is 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 present mutation of rBAT- gene on chromosome 2 (also SLC3A1, 2pter-q32.3), which for the heavy subunit of the Cystintransporters coded (molecular mass 90 kDa ). Affected people lack this transmembrane transport protein in the epithelial cells of the small intestine and in the proximal tubular cells , which reabsorbs cystine (the extracellular, oxidized form of cysteine ) and the above-mentioned amino acids from the primary urine . Consecutively, the excretion, especially of cystine, is increased to 20 to 30 times the norm, while the concentration in the blood remains unchanged.
Epidemiology
Cystinuria is a relatively rare disease with a prevalence of about 1: 20,000. According to another source, the prevalence of all three subclasses (types I to III) of classical cystinuria together is 1: 7000.
clinic
Cystine is the only one of the dibasic amino acids that has poor solubility at normal urine pH. From a concentration of ≥300 mg / l, precipitation occurs with the formation of hexagonal crystals in the urine or cystine stones in the urinary tract (about 1% of all urinary stones). 50% of all patients with cystinuria develop urinary stones, of which in turn 75% show a bilateral occurrence. Symptoms of nephrolithiasis , or urolithiasis , are colic-like pain in the area of the kidney bed with stone loss, which can radiate into the groin area. A hematuria can occur concomitantly, a urinary tract infection can complicate matters .
Diagnosis
The characteristic amino acid pattern in the urine is groundbreaking for cystinuria. The cyanide nitroprusside test can be used to qualitatively determine the amino acid cystine. A positive test indicates a concentration in the urine of over 75 mg / l and speaks for the diagnosis. A negative test excludes the presence of a cystinuria with a high probability. A molecular genetic examination provides definitive clarity. In many cases, however, the diagnosis is only made after the first manifestation of a stone disease, since the disease is asymptomatic beforehand. The diagnosis of urolithiasis includes, in addition to the typical anamnesis and clinical features, the urine status , sonography and urogram .
therapy
In the case of smaller oligosymptomatic stones, acute therapy is aimed at attempting medicinal lysis with D-penicillamine or α-mercaptopropionylglycine with increased fluid intake, diuresis and urinary alkalization. Otherwise, depending on the size of the stone, the entire urological-interventional or -operative spectrum is used ( ESWL = extracorporeal shock wave lithotripsy, PNL = percutaneous nephrolitholapaxy, etc.).
The actual therapy depends mainly on the prevention of chronic - recurrent stone disease to complications such. B. chronic urinary tract infections , renal insufficiency, etc. to avoid. The basis for this is a constantly high fluid intake, with a urine volume of ≥ 3 l / day to be achieved. To avoid the nocturnal aggregation of cystine crystals, fluids should also be administered at and during the night. Since cystine is readily water-soluble at a pH value of 7.5-8.0, urinary alkalization with this target range, e.g. B. with sodium bicarbonate orally, aimed at. D-penicillamine and α-mercaptopropionylglycine can also be used in prophylaxis, as they form more soluble disulfides with cystine . In this case, α-mercaptopropionylglycine is to be given preference due to the greater therapeutic range . A diet low in cystine and methionine can also be useful.
Cystinuria in animals
The disease is also known in dogs . The urinary stones that cause clinical symptoms are the most common, often in puppies as early as four to six months of age. Small to large stones and gravel can form in the kidneys and bladder, which lead to the organs becoming blocked. Without medical treatment (surgery), kidney failure, bladder rupture and possibly death of the animal will occur. Bitches are less affected than males, which can be explained by the narrower and longer urethra in the males. The genetic defect that leads to this cystinuria in some dog breeds is now known and the genetic defect can be detected immediately with the help of a DNA test. This test not only identifies animals that are already sick, but also clinically inconspicuous carriers that would spread this disease further in the population and cannot be detected with standard laboratory tests. Breeds known to date in which cystinuria occurs more frequently are Mastiffs , Newfoundlands , Irish Terriers and Kromfohrländer . A research project on cystinuria in Irish Terriers and Kromfohrländer is being carried out at the Institute for Genetics at the University of Bern in order to develop a breed-specific genetic test and to research the inheritance
Individual evidence
- ^ HUGO Gene Nomenclature Committee
- Jump up ↑ E. Fernández, M. Carrascal, F. Rousaud, J. Abián, A. Zorzano, M. Palacín, J. Chillarón: rBAT-b (0, +) AT heterodimer is the main apical reabsorption system for cystine in the kidney . In: Am J Physiol Renal Physiol. 2002 Sep; 283 (3), pp. F540-F548. PMID 12167606
- ^ Walter Siegenthaler , E. Blum: Clinical Pathophysiology. 9th edition. Thieme Verlag, Stuttgart 2006, ISBN 3-13-449609-7 , p. 122ff.
- ↑ Elaine Worcester: Cystine stones. UpToDate Ver. 17.3 September 2009.
- ↑ K. Ahmed, P. Dasgupta, MS Khan: Cystine calculi: challenging group of stones. In: Postgrad. Med. J. 2006; 82, pp. 799-801. PMID 17148700
- ↑ Research project for cystinuria when Kromfohrländer and Irish Terrier. Retrieved August 1, 2019 .
