A Case Report of Familial Renal Hypouricemia Confirmed by Genotyping of <i>SLC22A12</i>, and a Literature Review

Kim, Hyung Oh; Ihm, Chun-Gyoo; Jeong, Kyung Hwan; Kang, Hyun Joon; Kim, Jae-Min; Lim, Ho-Jin; Kim, Jin Sug; Lee, Tae Won

doi:10.5049/ebp.2015.13.2.52

Cited by 11 publications

(12 citation statements)

References 13 publications

(16 reference statements)

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“…In Korea, several cases of iRHUC caused by SLC22A12 mutations, showing homozygous W258X, are reported (Table 2) 19) . Only one case, Cheong et al 14) , out of four had no symptoms.…”

Section: Discussionmentioning

confidence: 99%

A Case of Idiopathic Renal Hypouricemia with SLC22A12 Gene Mutation Showing General Weakness and Incidental Renal Stone

et al. 2021

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Idiopathic renal hypouricemia (iRHUC) is a rare hereditary disease caused by a defect in urate handling of renal tubules. Type 1 renal hypouricemia (RHUC1) is diagnosed with confirmation of a mutation in SLC22A12 gene which encodes a renal urate-anion exchanger (URAT1). The majority of iRHUC patients are asymptomatic, especially during childhood, and thus many cases go undiagnosed or they are diagnosed late in older age with complications of hematuria, renal stones, or acute kidney injury (AKI). We report a case of a 7-year-old boy with subtle symptoms such as general weakness and dizziness and revealed hypouricemia and incidental nephrolithiasis. Homozygous mutations were detected in the SLC22A12 (c.774G>A) by molecular analysis. The present case suggests that fractional excretion of uric acid (FEUA) screening could be better followed by the coincidental discovery of hypouricemia, to prevent conflicting complications of iRHUC, even with normal urine uric acid to creatinine ratio (U UA /U Cr ), and sequential genetic analysis if needed.

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“…In Korea, several cases of iRHUC caused by SLC22A12 mutations, showing homozygous W258X, are reported (Table 2) 19) . Only one case, Cheong et al 14) , out of four had no symptoms.…”

Section: Discussionmentioning

confidence: 99%

A Case of Idiopathic Renal Hypouricemia with SLC22A12 Gene Mutation Showing General Weakness and Incidental Renal Stone

et al. 2021

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“…The SLC22A12 gene encodes a urate transporter in renal proximal tubules serving to reabsorb urate [14]. A SLC22A12 p.W258 � variant was first found in a Japanese patient with idiopathic renal hypouricemia and exercise-induced acute renal failure [14], and has been reported further in Korean and Japanese patients with hereditary renal hypouricemia [15,16]. In addition to patients with this Mendelian inherited disorder, the effects of p.W258 � on SUA https://doi.org/10.1371/journal.pone.0231336.g002…”

Section: Discussionmentioning

confidence: 99%

A population-specific low-frequency variant of SLC22A12 (p.W258*) explains nearby genome-wide association signals for serum uric acid concentrations among Koreans

Chae

Son

et al. 2020

PLoS ONE

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Prolonged hyperuricemia is a cause of gout and an independent risk factor for chronic health conditions including diabetes and chronic kidney diseases. Genome-wide association studies (GWASs) for serum uric acid (SUA) concentrations have repeatedly confirmed genetic loci including those encoding uric acid transporters such as ABCG2 and SLC9A2. However, many single nucleotide polymorphisms (SNPs) found in GWASs have been common variants with small effects and unknown functions. In addition, there is still much heritability to be explained. To identify the causative genetic variants for SUA concentrations in Korean subjects, we conducted a GWAS (1902 males) and validation study (2912 males and females) and found four genetic loci reaching genome-wide significance on chromosomes 4 (ABCG2) and 11 (FRMD8, EIF1AD and SLC22A12-NRXN2). Three loci on chromosome 11 were distributed within a distance of 1.3 megabases and they were in weak or moderate linkage disequilibrium (LD) states (r 2 = 0.02-0.68). In a subsequent association analysis on the GWAS loci of chromosome 11 using closely positioned markers derived from whole genome sequencing data, the most significant variant to be linked with the nearby GWAS signal was rs121907892 (c.774G>A, p.W258*) of the SLC22A12 gene. This variant, and each of the three GWAS SNPs, were in LD (r 2 = 0.06-0.32). The strength of association of SNPs with SUA concentration (negative logarithm of P-values) and the genetic distance (r 2 of LD) between rs121907892 and the surrounding SNPs showed a quantitative correlation. This variant has been found only in Korean and Japanese subjects and is known to lower the SUA concentration in the general population. Thus, this low-frequency variant, rs121907892, known to regulate SUA concentrations in previous studies, is responsible for the nearby GWAS signals.

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“…Several rare inherited disorders of XOR deficiency cause an abnormally low level of SUA and a high serum level of xanthine, termed hypouricemia and xanthinuria, respectively [ 27 ]. Hereditary genetic mutations of the urate transporter URAT1 (RHUC1) and glucose transporter 9 (GLUT9; RHUC2) have been reported to cause hypouricemia due to deficiency of reabsorption of kidney-filtered uric acid [ 28 , 29 ]. It may also be caused by uric acid oxidation due to treatment with uricase, or decreased renal tubular reabsorption due to acquired disorders [ 30 ] ( Figure 4 ).…”

Section: Hyperuricemiamentioning

confidence: 99%

Hyperuricemia-Related Diseases and Xanthine Oxidoreductase (XOR) Inhibitors: An Overview

2016

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Uric acid is the final oxidation product of purine metabolism in humans. Xanthine oxidoreductase (XOR) catalyzes oxidative hydroxylation of hypoxanthine to xanthine to uric acid, accompanying the production of reactive oxygen species (ROS). Uric acid usually forms ions and salts known as urates and acid urates in serum. Clinically, overproduction or under-excretion of uric acid results in the elevated level of serum uric acid (SUA), termed hyperuricemia, which has long been established as the major etiologic factor in gout. Accordingly, urate-lowering drugs such as allopurinol, an XOR-inhibitor, are extensively used for the treatment of gout. In recent years, the prevalence of hyperuricemia has significantly increased and more clinical investigations have confirmed that hyperuricemia is an independent risk factor for cardiovascular disease, hypertension, diabetes, and many other diseases. Urate-lowering therapy may also play a critical role in the management of these diseases. However, current XOR-inhibitor drugs such as allopurinol and febuxostat may have significant adverse effects. Therefore, there has been great effort to develop new XOR-inhibitor drugs with less or no toxicity for the long-term treatment or prevention of these hyperuricemia-related diseases. In this review, we discuss the mechanism of uric acid homeostasis and alterations, updated prevalence, therapeutic outcomes, and molecular pathophysiology of hyperuricemia-related diseases. We also summarize current discoveries in the development of new XOR inhibitors.

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A Case Report of Familial Renal Hypouricemia Confirmed by Genotyping of SLC22A12, and a Literature Review

Cited by 11 publications

References 13 publications

A Case of Idiopathic Renal Hypouricemia with SLC22A12 Gene Mutation Showing General Weakness and Incidental Renal Stone

A Case of Idiopathic Renal Hypouricemia with SLC22A12 Gene Mutation Showing General Weakness and Incidental Renal Stone

A population-specific low-frequency variant of SLC22A12 (p.W258*) explains nearby genome-wide association signals for serum uric acid concentrations among Koreans

Hyperuricemia-Related Diseases and Xanthine Oxidoreductase (XOR) Inhibitors: An Overview

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