Hereditary renal hypouricemia (HRH) is a rare genetic disorder that can go unnoticed until late age despite its onset during childhood. It is caused by genetic defects in the genes that encode renal uric acid transporters at the renal tubular level, which leads to a decrease in the reabsorption and/or increase in the secretion of uric acid. HRH should be suspected if there is a persistent serum uric acid level of less than 2 mg/dl, with a fractional excretion greater than 10% (normal 7.25 ± 2.98%). The definitive diagnosis of the disease is made by identifying a pathogenic variant in one of the 2 known genes: SCL22A12 (AR) and SLC2A9 (AD, AR).
- The SLC22A12 gene encodes the URAT1 transporter located in the apical membrane of the proximal tubule. It follows an autosomal recessive inheritance pattern.
- The SLC2A9 gene encodes the GLUT9 transporter, which has a long isoform that is expressed in the basolateral membrane of the proximal tubule, and another short one that is expressed in the apical membrane of the collecting duct. It follows a mainly recessive inheritance pattern but dominant forms have also been described.
Sometimes, the first manifestation may be hematuria or the discovery of hypercalciuria, but most of the time the diagnosis is made when one of its complications appears such as nephrolithiasis, or acute kidney damage induced by intense or less frequent physical exercise, after an episode. of dehydration due to acute gastroenteritis or posterior reversible encephalopathy syndrome in patients with exercise-associated CKD.
