Shengli Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
Fujian Provincial Hospital, Fuzhou 350001, China.
Biomed Res Int. 2021 May 10;2021:9973161. doi: 10.1155/2021/9973161. eCollection 2021.
Gitelman syndrome (GS) is an autosomal recessive inherited salt-losing renal tubular disease, which is caused by a pathogenic mutation of encoding thiazide-sensitive Na-Cl cotransporter, which leads to disturbance of sodium and chlorine reabsorption in renal distal convoluted tubules, resulting in phenotypes such as hypovolemia, renin angiotensin aldosterone system (RAAS) activation, hypokalemia, and metabolic alkalosis. In this study, two GS families with proteinuria or Hashimoto's thyroiditis were analyzed for genetic-phenotypic association. Sanger sequencing revealed that two probands carried compound heterozygous mutations, and proband A carried two pathogenic mutations: missense mutation Arg83Gln, splicing mutation, or frameshift mutation NC_000016.10:g.56872655_56872667 (gcggacatttttg>accgaaaatttt) in exon 8. Proband B carries two missense mutations: novel Asp839Val and Arg904Gln. Both probands manifested hypokalemia, hypomagnesemia, hypocalcinuria, metabolic alkalosis, and RAAS activation; in addition, the proband A exhibited decreased urinary chloride, phosphorus, and increased magnesium ions excretion, complicated with Hashimoto's Thyroiditis, while the proband B exhibited enhanced urine sodium excretion and proteinuria. The older sister of proband B with GS also had Hashimoto's thyroiditis. Electron microscopy revealed swelling and vacuolar degeneration of glomerular epithelial cells, diffuse proliferation of mesangial cells and matrix, accompanied by a small amount of low-density electron-dense deposition, and segmental fusion of epithelial cell foot processes in proband B. Light microscopy showed mild mesangial hyperplasia in the focal segment of the glomerulus, hyperplasia, and hypertrophy of juxtaglomerular apparatus cells, mild renal tubulointerstitial lesions, and one glomerular sclerosis. So, long-term hypokalemia of GS can cause kidney damage and may also be susceptible to thyroid disease.
格利森综合征（GS）是一种常染色体隐性遗传性失盐性肾小管疾病，由编码噻嗪敏感的钠-氯共转运体的致病突变引起，导致肾远曲小管钠和氯重吸收紊乱，表现为低血容量、肾素-血管紧张素-醛固酮系统（RAAS）激活、低钾血症和代谢性碱中毒等表型。本研究分析了两例伴有蛋白尿或桥本甲状腺炎的 GS 家系的遗传表型相关性。Sanger 测序显示，两名先证者均携带复合杂合突变，先证者 A 携带两个致病性突变：错义突变 Arg83Gln，剪接突变或移码突变 NC_000016.10：g.56872655_56872667（gcggacatttttg>accgaaaatttt）在 8 号外显子。先证者 B 携带两个错义突变：新的 Asp839Val 和 Arg904Gln。两名先证者均表现为低钾血症、低镁血症、低钙尿症、代谢性碱中毒和 RAAS 激活；此外，先证者 A 还表现为尿氯、磷减少，镁离子排泄增加，伴有桥本甲状腺炎，而先证者 B 表现为尿钠排泄增加和蛋白尿。先证者 B 的 GS 姐姐也患有桥本甲状腺炎。电镜下，先证者 B 的肾小球上皮细胞肿胀，空泡变性，系膜细胞和基质弥漫增生，伴有少量低密度电子致密物沉积，上皮细胞足突节段融合。光镜下，肾小球局灶节段性系膜细胞轻度增生，肾小球旁器细胞增生、肥大，轻度肾小管间质病变，1 个肾小球硬化。因此，GS 的长期低钾血症可导致肾脏损害，也可能易患甲状腺疾病。
