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Cystinuria is an inherited disorder that affects the renal reabsorption of cystine, which leads to abnormally high-cystine levels in the urine with a significantly increased risk of recurrent urolithiasis already at a young age.
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Overall, estimated to be in the range of 1:7,000. However, a wide geographical variability has been reported (eg, 1:2,500 in Libyan Jews, 1:15,000 in Americans, 1:100,000 in Sweden). Due to incomplete penetrance (patients with the genetic defect but do not develop urolithiasis), the real numbers might be significantly higher. Both genders are equally affected, but the clinical course in males seems to be more aggressive (earlier onset and higher number of stones).
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Autosomal recessive and autosomal dominant inheritance have been described. On a molecular genetic level, two types of Cystinuria can be distinguished: Cystinuria Type A is most often autosomal recessive inherited and caused by mutations in the SLC3A1 (Solute Carrier Family 3 Member 1; Cystine, Dibasic, and Neutral Amino Acid Transporter) gene, which has been mapped to chromosome 2p21. Cystinuria Type B is most often autosomal dominant inherited and the result of mutations in the SLC7A9 (Solute Carrier Family 7 Member 9; Cationic Amino Acid Transporter, γ+ System) gene located on chromosome 19q13.11. If a patient inherits a mutated SLC3A1 gene from one parent and a mutated SLC7A9 gene from the other, then that patient would be referred to as Cystinuria Type AB. Type A, B, and AB account for 38%, 47%, and 14% of all Cystinuria cases, respectively. (Other, less straightforward classification systems have been used.) Combined, more than 150 mutations have been described in these two genes to date.
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Based on the clinical findings and family history. Microscopically, characteristic hexagonal and flat cystine crystals in the urine can be detected in about a quarter of all Cystinuria patients. Renal ultrasound, x-ray, or CT-scanning can be used to confirm and assess stones that can form anywhere along the urinary tract and lead to obstructive uropathy. The sodium-cyanide-nitroprusside test can be used for qualitative assessment of the urine cystine concentration. Cyanide breaks the disulfide-bond of cystine and the newly formed cysteine then binds to nitroprusside causing a red-purple color change within less than 10 minutes. The diagnosis can be confirmed by quantitative measuring of urinary cystine excretion, which in Cystinuria is often higher than 1,000 µmol/g creatinine. Immaturity and incomplete expression of the renal amino acid transporters (known as transient neonatal Cystinuria) in heterozygous patients require caution when interpreting the results in children less than 2 to 4 years of age.
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Normally, more than 99% of glomerularly filtrated cystine is reabsorbed by the amino acid transporter in the apical membrane of renal proximal tubular cells. Once inside the proximal tubular cell, cystine is broken up into ...