Cystinuria in Clinical Practice: Challenges in Genetic Verification and Laboratory Diagnosis

Abstract

Cystinuria is an inherited disorder caused by impaired reabsorption of cystine and dibasic amino acids - ornithine, lysine, arginine - in the proximal renal tubules. The genetic basis of cystinuria involves mutations in the SLC3A1 gene (encoding the heavy subunit of the rBAT transporter) and the SLC7A9 gene (encoding the light subunit b^0,+AT). Dysfunction of the rBAT-b^0,+AT transporter leads to excessive cystine excretion, which has low solubility at physiological urine pH, promoting the formation of calculi. The inheritance pattern of cystinuria varies: mutations in SLC3A1 typically follow an autosomal recessive mode, whereas mutations in SLC7A9 exhibit a broader spectrum, ranging from recessive to dominant inheritance. Notably, approximately 10% of patients lack detectable mutations in these genes, suggesting the potential involvement of non-coding regulatory regions or modifier genes. This review synthesizes current understanding of renal cystine transport and explores complex clinical cases that deviate from the classical autosomal recessive model associated with SLC3A1 mutations.