Reference values of urinary excretion of cystine and dibasic aminoacids: Classification of patients with cystinuria in the Valencian Community, Spain

Objective: Cystinuria is an autosomal-recessive disorder of the kidneys and small intestine affecting a luminal transport mechanism shared by cystine, ornithine, arginine, and lysine. Three different types of cystinuria can b e distinguished according to the excretion of these amino acids in urine sa mples. We propose cutoff values from our population as references and we pr esent a classification of cystinuric patients using quantitative amino acid chromatography in first morning urine samples. Design and methods: A random sample of forty healthy subjects belonging to general population of the Valencian Community were selected as control subj ects. Cystine, lysine, arginine, and ornithine were quantified by reverse-p hase HPLC. Seventy-two subjects, diagnosed previously as cystinuric by the cyanide-nitroprusside test were classified. Probands excreting more than 11 3.12 mu mol cystine per mmol of creatinine (i.e., 1,000 mu mol cystine per gram of creatinine) were classified as homozygotes. Parents of homozygotes in whom excretion of amino acids were normal were classified as heterozygot es type I. Those probands showing the excretion of at least one amino acid and the sum of urinary cistine plus the basic amino acids higher than the c orresponding references ranges in our population were classified as heteroz ygotes type II or type III (heterozygotes non-type I). Results: We identified 24 homozygotes, 39 non-type I heterozygotes and 3 ty pe I heterozygotes. The remaining 6 probands could not be classified. Means for cystine, lysine, arginine ornithine and their sum in homozygotes and h eterozygotes non-type I were significantly (p < 0.001) in excess of the res pective reference ranges. Moreover, means values in homozygotes were statis cally different (p < 0.001) from heterozygotes non-type I. Conclusion: Urinary excretion of cystine per mmol creatinine allow us to di stinguish heterozygotes from homozygotes. However, the best discriminator t o distinguish non-type I heterozygotes from normal population might be the excretion of lysine per mmol creatinine. Additional studies including chara cterization of appropiate haplotypes should be carried out for a more preci se identification of types of cystinuria. Copyright (C) 1999 The Canadian S ociety of Clinical Chemists.