He Guangyu, Gang Xiaokun, Sun Zhonghua, Wang Ping, Wang Guixia, Guo Weiying
Department of Endocrinology and Metabolism.
Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University, Changchun, Jilin, P.R. China.
Medicine (Baltimore). 2020 Jul 17;99(29):e21123. doi: 10.1097/MD.0000000000021123.
Gitelman syndrome (GS) is an autosomal-recessive disease caused by SLC12A3 gene mutations. It is characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Recently, patients with GS are found at an increased risk for developing type 2 diabetes mellitus (T2DM). However, diagnosis of hyperglycemia in GS patients has not been thoroughly investigated, and family studies on SLC12A3 mutations and glucose metabolism are rare. Whether treatment including potassium and magnesium supplements, and spironolactone can ameliorate impaired glucose tolerance in GS patients, also needs to be investigated.
We examined a 55-year-old Chinese male with intermittent fatigue and persistent hypokalemia for 17 years.
Based on the results of the clinical data, including electrolytes, oral glucose tolerance test (OGTT), and genetic analysis of the SLC12A3 gene, GS and T2DM were newly diagnosed in the patient. Two mutations of the SLC12A3 gene were found in the patient, one was a missense mutation p.N359K in exon 8, and the other was a novel insert mutation p.I262delinsIIGVVSV in exon 6. SLC12A3 genetic analysis and OGTT of 9 other family members within 3 generations were also performed. Older brother, youngest sister, and son of the patient carried the p.N359K mutation in exon 8. The older brother and the youngest sister were diagnosed with T2DM and impaired glucose tolerance by OGTT, respectively.
The patient was prescribed potassium and magnesium (potassium magnesium aspartate, potassium chloride) oral supplements and spironolactone. The patient was also suggested to maintain a high potassium diet. Acarbose was used to maintain the blood glucose levels.
The electrolyte imbalance including hypokalemia and hypomagnesemia, and hyperglycemia were improved with a remission of the clinical manifestations.
GS is one of the causes for manifestation of hypokalemia. SLC12A3 genetic analysis plays an important role in diagnosis of GS. Chinese male GS patients characterized with heterozygous SLC12A3 mutation should be careful toward occurrence of T2DM. Moreover, the patients with only 1 SLC12A3 mutant allele should pay regular attention to blood potassium and glucose levels. GS treatment with potassium and magnesium supplements, and spironolactone can improve impaired glucose metabolism.
吉特林综合征（GS）是一种由SLC12A3基因突变引起的常染色体隐性疾病。其特征为低钾性代谢性碱中毒，同时伴有低镁血症和低钙尿症。最近发现，GS患者患2型糖尿病（T2DM）的风险增加。然而，GS患者高血糖的诊断尚未得到充分研究，关于SLC12A3突变与糖代谢的家族研究也很少见。包括补充钾和镁以及使用螺内酯在内的治疗方法能否改善GS患者受损的糖耐量，也有待研究。
我们检查了一名55岁的中国男性，他有间歇性疲劳症状，持续低钾血症达17年。
根据临床数据结果，包括电解质、口服葡萄糖耐量试验（OGTT）以及SLC12A3基因的基因分析，该患者被新诊断出患有GS和T2DM。在该患者中发现了SLC12A3基因的两个突变，一个是外显子8中的错义突变p.N359K，另一个是外显子6中的新插入突变p.I262delinsIIGVVSV。还对该患者三代以内的其他9名家庭成员进行了SLC12A3基因分析和OGTT。患者的哥哥、妹妹和儿子在外显子8中携带p.N359K突变。哥哥和妹妹分别通过OGTT被诊断为T2DM和糖耐量受损。
给患者开了钾和镁（门冬氨酸钾镁、氯化钾）口服补充剂以及螺内酯。还建议患者保持高钾饮食。使用阿卡波糖来维持血糖水平。
包括低钾血症和低镁血症在内的电解质失衡以及高血糖得到改善，临床表现缓解。
GS是低钾血症表现的原因之一。SLC12A3基因分析在GS诊断中起重要作用。具有SLC12A3杂合突变特征的中国男性GS患者应警惕T2DM的发生。此外，仅有1个SLC12A3突变等位基因的患者应定期关注血钾和血糖水平。补充钾和镁以及使用螺内酯治疗GS可改善受损的糖代谢。
