Medical School, University Children's Hospital, Skopje, Macedonia.
PLoS One. 2011;6(12):e28641. doi: 10.1371/journal.pone.0028641. Epub 2011 Dec 16.
Idiopathic renal hypouricaemia is an inherited form of hypouricaemia, associated with abnormal renal handling of uric acid. There is excessive urinary wasting of uric acid resulting in hypouricaemia. Patients may be asymptomatic, but the persistent urinary abnormalities may manifest as renal stone disease, and hypouricaemia may manifest as exercise induced acute kidney injury. Here we have identified Macedonian and British patients with hypouricaemia, who presented with a variety of renal symptoms and signs including renal stone disease, hematuria, pyelonephritis and nephrocalcinosis. We have identified heterozygous missense mutations in SLC22A12 encoding the urate transporter protein URAT1 and correlate these genetic findings with functional characterization. Urate handling was determined using uptake experiments in HEK293 cells. This data highlights the importance of the URAT1 renal urate transporter in determining serum urate concentrations and the clinical phenotypes, including nephrolithiasis, that should prompt the clinician to suspect an inherited form of renal hypouricaemia.
特发性肾低尿酸血症是一种遗传性低尿酸血症，与尿酸在肾脏的异常处理有关。尿酸在尿液中过度流失，导致低尿酸血症。患者可能无症状，但持续的尿液异常可能表现为肾结石疾病，低尿酸血症可能表现为运动引起的急性肾损伤。在这里，我们发现了马其顿和英国的低尿酸血症患者，他们表现出各种肾脏症状和体征，包括肾结石疾病、血尿、肾盂肾炎和肾钙质沉着症。我们在编码尿酸转运蛋白 URAT1 的 SLC22A12 中发现了杂合错义突变，并将这些遗传发现与功能特征相关联。尿酸处理是通过在 HEK293 细胞中进行摄取实验来确定的。这些数据强调了 URAT1 肾脏尿酸转运蛋白在确定血清尿酸浓度和临床表型中的重要性，包括肾结石，这应该促使临床医生怀疑是遗传性肾低尿酸血症。
