Diagnostic and genetic studies in 43 patients with classic cystinuria

We present results for laboratory screening and diagnostic tests--cyanide-nitroprusside test, semi-quantitative thin-layer chromatography, and quantitative amino acid column chromatography--of 43 patients with classic cystinuria. We report the efficaciousness of the cyanide-nitroprusside test and of thin-layer chromatography, as compared with quantitative amino acid chromatography, for detecting heterozygotes for type II or III cystinuria. The quantitative results for aminoaciduria in 57 blood relatives in 23 families were used to categorize the index patients with classic cystinuria. By column chromatography the ranges of excretion rates (mumol/24 h per 1.73 m2 body surface area) of diagnostic amino acids in the index patients were as follows: cystine 556-54044 (normal 20-128), arginine 131-11543 (10-80), lysine 768-21848 (51-514), ornithine 185-5685 (0-80). Also by column chromatography the median values for arginine and ornithine excretion in cystine-lysinuric heterozygotes (among the 57 blood relatives) were significantly higher (P less than 0.01) than in controls but never approached the values for homozygotes. The cyanide-nitroprusside test results were positive in urine samples of 41 of 43 index patients and in 16 (51.6%) of the urine samples of 31 obligate heterozygotes with column chromatographically proven cystine-lysinuria. Thin-layer chromatography detected all of the homozygotes, all the compound heterozygotes, and 54.8% of the carriers. According to the type of aminoaciduria in their relatives, 11 patients with classic cystinuria could be classified as having classic cystinuria type I, 11 as having type II or III, and three as being compound heterozygotes. We discuss the implications of these results for correct diagnoses and for genetic studies in classic cystinuria.