Renal polyamine excretion, tubular amino acid reabsorption and molecular genetics in cystinuria

Cystinuria is an autosomal recessive disorder of the tubular and intestinal resorption of cystine, ornithine, lysine and arginine leading to nephrolit hiasis. Three cystinuria types can be distinguished by the mode of inherita nce (true recessive or intermediate) and by the pattern of the intestinal a mino acid transport. In the present study phenotypes were assessed by the u rinary excretion of amino acids related to creatinine, the percentage tubul ar amino acid reabsorption and the urinary excretion of polyamines as a pos sible indicator of the intestinal transport defect. However, our thorough p henotyping did not reveal more than two cystinuria types. Genotypes were ex amined in linkage analyses and single-strand conformation polymorphism-base d mutation identification. The SLC3A1 mutations M467T and T216M were diseas e causing in our homozygous patients of type I cystinuria. We can show the association of type I cystinuria with SLC3A1 and of non-type I cystinuria w ith a yet unidentified gene on chromosome 19q13.1. Our phenotype and genoty pe analyses provide evidence for only two types of cystinuria in the invest igated patient cohort.