Metabolic defect: inactivating mutation in 1 of the 2 dibasic aminoacid transporter subunits (rBAT or b0+AT1) in the kidney
Amino acids affected: arginine, cystine, lysine, ornithine
Limit of cystine solubility: 1.33 mmol/L at pH 6.0, but rises sharply when the pH is greater than 7
Cystine concentration in the urine is increased by:
(1) concentrated urine (dehydration, other)
(2) high intake of animal proteins
(3) high salt intake
The presence of increased calcium, oxalate and/or urate in the urine will increase the risk of stone formation.
Cystine solubility is improved by:
(1) an alkaline pH
(2) conversion of cystine to cysteine
(3) urine dilution
Diagnostic features:
(1) early age of onset for stone disease (typically in young adult although homozygous patients may present in infancy)
(2) family history of cystinuria
(3) hexagonal cystine crystals seen on urinalysis (may be absent in an alkaline urine)
(4) elevated cystine on 24 hour urine
(5) X-rays show a mildly radio-opaque stone with a milk-glass-like shadow
(6) ultrasonography shows a typical echo
(7) high levels of cystine identified on stone analysis
Urine measurement indicating hypercystinuria:
(1) > 150 micromol cystine per mmol creatinine
(2) > 0.33 mmol cystine per 24 hour (treatment is started when >= 0.8 mmol per 24 hours)
where:
• The molecular weight of cystine is 240.30 grams. 1 mmol = 240.3 mg.
• Conversion factor for cystine: mg/dL * 41.6 = µmol/L; mg/dL * 0.0416 = mmol/L
