Cystinuria is an hereditary disorder of renal and intestinal transport characterized by the excessive urinary excretion of
cystine,
arginine, lysine, and
ornithine. It is inherited as a common recessive gene with allelic mutations. Complementary studies of the plasma response to oral
cystine loading, intestinal mucosal transport patterns, and urine
cystine excretion allow separation of homozygous cystinuric subjects into three groups. In type I, the most common form, there is no active transport of
cystine or
dibasic amino acids across the mucosal gradient, and heterozygous subjects show normal urine
cystine values. Type II is characterized by markedly reduced or absent intestinal transport of
cystine. Heterozygotes for type II show significantly elevated urine
cystine but less than is seen in homozygotes. In type III there is diminished, although demonstrable, intestinal absorption of
cystine and
dibasic amino acids. Urine
cystine in heterozygotes is intermediate between types I and II.
Urolithiasis with its attendant complications is the sole clinical manifestation of
cystinuria and is due to the relative insolubility of
cystine in the urine. The
urolithiasis may become clinically manifest at any time from infancy through the ninth decade, although the mean age is the second to third decade. Clinical presentation is similar to that of other types of
urolithiasis. Although
cystinuria accounts for only 1% to 2% of all
urolithiasis and 6% to 8% of
urolithiasis in pediatric populations, repeated stone formation in affected patients often causes considerable morbidity.
Cystine crystals in the urine are diagnostic but show up in only 19% to 26% of homozygous cystinuric patients.
Sodium cyanide nitroprusside is a suitable screening test that should identify homozygous stone formers but will not detect all heterozygotes. A positive screening test should be followed by quantitation of urinary
amino acids. A homozygous patient can be functionally defined as one who excretes 250 mg or more of
cystine/g of
creatinine in a 24-hour urine collection. Other causes of excess urinary
cystine must be excluded. Medical
therapy will be directed toward dissolution of existing
calculi and prevention of new stone formation. Increasing urine volume by generous oral fluid intake is beneficial.
Dietary sodium restriction has a favorable effect on urinary
cystine excretion.
Cystine solubility can be improved by urinary alkalinization and where necessary by the administration of
thiol chelators, particularly
D-penicillamine or
mercaptopropionylglycine. Because these
chelators have significant adverse effects, they should be reserved for patients who do not respond to a more conservative program. Patients with infected, symptomatic, or obstructing stones require surgical intervention.(ABSTRACT TRUNCATED AT 400 WORDS)