2. congenital hypouricemia: individuals with the autosomal recessive disease hereditary xanthinuria have mutations in the gene encoding xanthine oxidase and as a result accumulate the uric acid precursors xanthine, which is fairly insoluble. As a result, individuals with hereditary xanthinuria develop xanthine nephrolithiasis and myopathy due to xanthine deposits in muscle, and typically have a profoundly low serum uric acid level.
3. liver failure: as a majority of xanthine oxidase is synthesized in the liver, individuals with severe cirrhotic liver disease may have a low serum uric acid level.
II. Decreased renal uric acid reabsorption.
1. Fanconi's Syndrome/proximal tubule dysfunction: since a majority of renal uric acid reabsorption occurs in the proximal tubule, it makes sense that any type of proximal tubular dysfunction will lead to hypouricemia (along with a host of other metabolic abnormalities such as proteinuria, glucosuria, aminoaciduria, hyphosphatemia, etc.)
2. SIADH: a clinical pearl often helpful in the diagnosis of SIADH is that it is very often associated with a very low serum uric acid level, allowing one to distinguish SIADH from other causes of hyponatremia. One possible mechanism for this is that ADH stimulating V1 receptors reduces renal uric acid uptake; this is based on the observation that individuals with SIADH experience a more profound hypouricemia than patients treated with ddAVP (which should selectively stimulate the V2 receptor).
3. Drugs. Some drugs can induce hypouricemia, including probenicid (a direct inhibitor of the organic anion transporter which is responsible for the tubular reabsorption of uric acid) and Bactrim, for instance.
4. Familial Renal Hypouricemia: this is a rare congenital disorder (most common in non-Ashkenazi Jews and Japenese individuals) caused by loss-of-function mtuations in the organic anion exchanger; individuals can exhibit a fractional excretion of uric acid that is greater than 95% due to an inability to reabsorb uric acid. Not surprisingly, these individuals are at high risk for urate nephrolithiasis.