Genotype and Phenotype of Renal Hypouricemia: A Single-Center Study from China.

Abstract

Renal hypouricemia (RHUC), a rare inherited disorder characterized by impaired uric acid reabsorption and subsequent profound hypouricemia, occurs mainly due to variants in SLC22A12 or SLC2A9. Only anecdotal cases and one small-scale RHUC screening study have been reported in the Chinese population. A total of 19 patients with RHUC from 17 unrelated families were recruited from our center. The medical history, clinical manifestations, biochemical exam, and clinical outcomes were collected. Next-generation sequencing-based targeted gene sequencing or whole exon sequencing was performed. A total of 22 variants in SLC22A12 or SLC2A9 were found in 19 patients. The variant c.944G>A (p.W315X) in SLC2A9 was identified in three patients. Three variants c.165C>A (p.D55E), c.1549_1555delGAGACCC (p.E517Rfs*17), and c.1483T>C (p.W495R) in SLC22A12 and three variants c.1215+1G>A (splicing variant), c.643A>C (p.T215P), and c.227C>A (p.S76X) in SLC2A9 were novel. A proportion of 10 out of 19 patients presented with exercise-induced acute kidney injury (EIAKI). The renal outcome was favorable. Five patients had nephrolithiasis, in whom three had hypercalciuria. The current study reported six novel variants in SLC22A12 and SLC2A9 genes of Chinese patients with RHUC. The variant c.944G>A (p.W315X) in SLC2A9 may be common in Chinese patients. EIAKI is the main clinical phenotype associated with RHUC in our cohort, with a favorable outcome. Hypercalciuria presented in some RHUC patients is a new finding.