Abstract:

Objective To explore the clinical features, diagnosis and treatment points and genetic factors of cystinuria by analyzing a family with cystinuria. Methods The proband was a 28-year-old male, and the data of the family with cystinuria was retrospectively analyzed. The stone composition of the proband was determined by urine sediment microscopy, energy spectrum CT and infrared spectroscopy. The peripheral blood DNA samples of the proband and family members were extracted and captured by the target sequence. High-throughput sequencing technology was used to screen mutant genes, and the progress of diagnosis and treatment of cystinuria was discussed referring to literatures. Results The proband in this family was firstly diagnosed at 15 years old. His main clinical manifestation was recurrent left urinary tract calculi combined with proteinuria. The mother’s main manifestation was proteinuria, and the father had no symptoms related to kidney. The sequencing results showed that the proband had a compound heterozygous mutation in the solute carrier family 3, member 1(SLC3A1) gene, including the frameshift mutation NM_000341:exon3:c.703delG ( mother was the carrier of the heterozygous mutation) and missense mutation NM_000341:exon8:c.1366C>T (father is a carrier of the heterozygous mutation). According to American College of Medical Genetics and Genomics(ACMG) guidelines, both mutations were classified as suspected pathogenic variants. The proband had a history of multiple ureteroscopic lithotripsy, and specific hexagonal crystals could be found in urine sedimentary mirror examination and the stone composition was determined to be L-cystine by spectrum CT. After being diagnoses as cystinuria, the proband was treated with alkalization of urine and proteinuria, and his current condition was stable. Conclusions A specific diagnostic method for cystinuria is to find hexagonal crystals in urine sediment microscopy. Spectrum CT can be applied to diagnose cystine stones non-invasively. Genetic disease should be strongly considered in the patients with recurrent stones at young age, and genetic testing can be used as etiological diagnosis method for cystinuria.

Key words: Cystinuria, Nephrolithiasis, Compound heterozygosity, Gene sequencing