Pathogenesis and medical management of cystinuria

Cystinuria is an inheritable disorder of amino acid transport, transmitted as an autosomal recessive trait. Cystinuria is caused by defective transport of cystine and dibasic amino acids through the epithelial cells of the renal tubule and intestinal tract. Cystine stones are caused by the excessive renal excretion of cystine as a result of its low solubility in urine. Recently, a human kidney cDNA, named rBAT (also D2: the gene now designated SLC3A1), which elicits the transport for cystine and dibasic amino acids, has been reported. The 90-kd Type II glycoprotein stimulated cystine and dibasic and neutral amino acid uptake into oocytes with kinetics similar to the renal brush border transporter. The human gene for this protein resides on chromosome 2. The most frequent mutations found involved substitution of the threonine for methionine 467. Eight additional mutations in SLC3A1 have been found. Cystine stones frequently occur in the second or third decade of life, with an occasional occurrence in infancy and in old age. Urinary cystine excretion exceeding 250 mg/g creatinine is usually diagnostic of homozygous cystinuria. The goal of treatment is to reduce the urinary cystine concentration below its solubility limit (250 mg/L).