cystinuria

Cystinuria is a renal tubular amino acid transport disorder that results in the recurrent formation of cystine kidney stones. It is linked to changes in the SLC3A1 and SLC7A9 genes, which affect the reabsorption of cystine and other amino acids in the kidney. This condition can affect individuals of both sexes and may present at various ages. In terms of prevalence, cystinuria is considered relatively common among rare diseases, affecting approximately 1 to 5 per 10,000 people.

Individuals with cystinuria most commonly experience recurrent kidney stones and related symptoms such as hematuria and abnormalities in amino acid metabolism, which are observed in a high proportion of cases. Other frequently reported features include hypertension, nausea and vomiting, hyperuricemia, abnormal urinary odor, hypocitraturia, flank pain, and the presence of cystine crystals in the urine. Less commonly, some patients may also exhibit hypercalciuria and hyperuricosuria. Not all individuals experience all features, and severity varies considerably.

Cystinuria is caused by pathogenic variants in the SLC3A1 and SLC7A9 genes, both of which code for transport proteins that facilitate the reabsorption of cystine and other amino acids in the kidney. Disruption in the function of these proteins leads to an excess of cystine in the urine and promotes stone formation. The condition has been reported with both autosomal recessive and autosomal dominant patterns of inheritance, meaning that in some families, the condition can be inherited when both copies of a gene are altered or even when a single altered copy is present. Families are encouraged to seek genetic counseling to better understand the implications of these inheritance patterns for family planning and recurrence risk.

Currently, management of cystinuria focuses on supportive care and symptom management, as no treatments have been specifically approved or designated for this condition. Treatment strategies typically emphasize increased fluid intake, dietary modifications, and measures to control cystine concentrations in the urine, all tailored to the individual’s needs. A multidisciplinary team approach is often employed, and patients are encouraged to discuss treatment options with their healthcare team. Genetic counseling is also recommended to help families understand the inheritance and long-term management of the condition.

The clinical course of cystinuria is highly variable, with outcomes depending on factors such as symptom severity, age at diagnosis, and how well an individual responds to supportive care. With current standards of care, many individuals can manage recurring kidney stone events and maintain a good quality of life into adulthood. It is important to recognize that outcomes described in medical literature continue to evolve as standards of care improve, and variability is common among affected individuals. Families often find it helpful to connect with specialists experienced in this condition and pursue genetic counseling for ongoing support and guidance.

Clinical trials are underway exploring new treatment approaches for cystinuria, and this remains an active area of research. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.