Cystinuria is caused by pathogenic variants in two genes: SLC7A9, located on chromosome 19, and SLC3A1, located on chromosome 2. Both have received a DEFINITIVE gene-disease validity classification from ClinGen, the authoritative evidence-based framework for assessing such relationships.

The condition can follow either an autosomal recessive or an autosomal dominant inheritance pattern depending on the genotype. Cystinuria type A arises from biallelic SLC3A1 pathogenic variants and follows an autosomal recessive pattern, requiring two altered copies of the gene — one from each parent — to cause the condition; carrier parents each face a 25% probability per pregnancy of having an affected child. Cystinuria type B arises from biallelic SLC7A9 pathogenic variants and likewise follows an autosomal recessive pattern. However, individuals who carry only a single SLC7A9 pathogenic variant may also develop cystinuria, reflecting an autosomal dominant pattern with high penetrance.

GeneReviews documents founder variants in SLC3A1 in Ashkenazi Jewish and Mennonite populations, and founder variants in SLC7A9 in Libyan Jewish and Mennonite populations.

According to GeneReviews, clinical diagnostic criteria for cystinuria were established through a consensus conference held in January 2019, developed by experts from the Metabolic Nephropathy Joint Working Group of the European Reference Network for Rare Kidney Diseases (ERKNet) and eUROGEN members, consistent with a United States consensus statement. GeneReviews indicates that clinical suspicion arises in individuals with early-onset kidney stones exhibiting characteristic clinical, laboratory, and imaging findings, including cystine crystalluria. Molecular genetic testing of SLC3A1 and SLC7A9 provides the basis for genetic confirmation. GeneReviews also documents a differential diagnosis framework for the condition. No newborn screening data is documented for this condition in this packet.

The primary therapeutic goal in cystinuria, as described in GeneReviews, is the reduction of urinary cystine concentration below its solubility threshold. This is achieved through alkalinization of the urine — which increases cystine solubility — combined with increased fluid intake to dilute urinary cystine and reduction of dietary sodium and animal protein intake.

Penicillamine is an FDA-approved treatment for cystinuria, commercially available under the brand names DEPEN and CUPRIMINE, both with active market status under approval from the FDA's Center for Drug Evaluation and Research (CDER). Penicillamine is a chelating therapy that reduces urinary cystine concentration.

Several additional therapies are under investigation and carry orphan drug designation but have not received FDA approval: bucillamine (Revive Therapeutics), L-cystine bis(N'-methylpiperazide) (PharmaKrysto), L-ergothioneine (AVEROA), and potassium citrate and potassium bicarbonate (Advicenne). GeneReviews also references ongoing investigation of alpha-lipoic acid supplementation in a randomized controlled trial setting.

GeneReviews identifies certain high-methionine foods — including liver, poultry, and selected fish preparations — as associated with elevated cystine levels, along with dietary and hair supplements with high methionine concentrations.

Patient assistance programs may be available to help cover treatment costs.

GeneReviews documents that the clinical course of cystinuria is defined by early-onset and recurrent cystine kidney stone formation. Long-term complications reported by GeneReviews include recurrent urinary tract infections, chronic kidney disease, and hypertension. GeneReviews notes that some individuals develop end-stage kidney disease over time. The frequency of recurrent stone events and the development of progressive kidney disease are the primary drivers of long-term morbidity documented in this packet. No specific mortality figures or life expectancy estimates are included in the available data.

Several certified active trial records are present for cystinuria. The Mayo Clinic is conducting two long-term studies: the Rare Kidney Stone Consortium Biobank (NCT02026388), an actively recruiting biospecimen collection effort expected to continue through 2030, and the Rare Kidney Stone Consortium Patient Registry (NCT00588562), also actively recruiting through 2028. The Prospective Research in Rare Kidney Stones study (NCT02780297) is additionally recruiting at Mayo Clinic through 2026. Research modalities documented in this packet span observational, procedural, and other intervention types, with academic institution sponsors predominating. GeneReviews references a randomized controlled investigation of alpha-lipoic acid supplementation in adults with cystinuria (NCT02910531), noting preliminary results from that study. Active clinical trials for this condition are listed on ClinicalTrials.gov.