Definition
Cystinuria is an autosomal recessive disorder of the transporter that reabsorbs dibasic amino acids — cystine, ornithine, lysine and arginine (COLA) — in the proximal tubule and gut. Because cystine is poorly soluble, it precipitates to form recurrent renal stones.
Genetics
Mutations in SLC3A1 or SLC7A9 impair the shared transporter. Only cystine causes clinical problems (the others are soluble).
Clinical presentation
- Recurrent renal stones from a young age
- Renal colic, haematuria, and complications of obstruction/infection
- Stones are radio-opaque (though less so than calcium stones)
Investigations
- Urine microscopy: hexagonal crystals
- Positive cyanide-nitroprusside screening test
- Raised 24-hour urinary cystine
- Imaging for stone burden
Management
- High fluid intake to keep cystine dilute (large daily urine volumes)
- Urinary alkalinisation with potassium citrate (cystine is more soluble at higher pH)
- Chelating/thiol agents (D-penicillamine, tiopronin) for severe or refractory disease
- Urological intervention for obstructing stones
MRCP-specific traps
- Hexagonal crystals are essentially pathognomonic of cystinuria.
- Suspect it in recurrent stones starting in childhood/adolescence with a family history.
- Do not confuse cystinuria (a transport defect causing stones) with cystinosis (lysosomal storage disease causing Fanconi syndrome).
Summary
Cystinuria is a recessive dibasic amino-acid transport defect (COLA) causing recurrent, poorly soluble cystine stones with hexagonal crystals. Manage with high fluid intake, urinary alkalinisation and, if needed, thiol chelators.
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