Fujimura Junya, Nozu Kandai, Yamamura Tomohiko, Minamikawa Shogo, Nakanishi Keita, Horinouchi Tomoko, Nagano China, Sakakibara Nana, Nakanishi Koichi, Shima Yuko, Miyako Kenichi, Nozu Yoshimi, Morisada Naoya, Nagase Hiroaki, Ninchoji Takeshi, Kaito Hiroshi, Iijima Kazumoto
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Child Health and Welfare (Pediatrics), Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Kidney Int Rep. 2018 Sep 28;4(1):119-125. doi: 10.1016/j.ekir.2018.09.015. eCollection 2019 Jan.
Gitelman syndrome (GS) is a tubulopathy exhibited by salt loss. GS cases are most often diagnosed by chance blood test. Aside from that, some cases are also diagnosed from tetanic symptoms associated with hypokalemia and/or hypomagnesemia or short stature. As for complications, thyroid dysfunction and short stature are known, but the incidence rates for these complications have not yet been elucidated. In addition, no genotype-phenotype correlation has been identified in GS.
We examined the clinical characteristics and genotype-phenotype correlation in genetically proven GS cases with homozygous or compound heterozygous variants in ( = 185).
In our cohort, diagnostic opportunities were by chance blood tests (54.7%), tetany (32.6%), or short stature (7.2%). Regarding complications, 16.3% had short stature, 13.7% had experienced febrile convulsion, 4.3% had thyroid dysfunction, and 2.5% were diagnosed with epilepsy. In one case, QT prolongation was detected. Among 29 cases with short stature, 10 were diagnosed with growth hormone (GH) deficiency and GH replacement therapy started. Interestingly, there was a strong correlation in serum magnesium levels between cases with p.Arg642Cys and/or p.Leu858His and cases without these variants, which are mutational hotspots in the Japanese population (1.76 mg/dl vs. 1.43 mg/dl, < 0.001).
This study has revealed, for the first time, clinical characteristics in genetically proven GS cases in the Japanese population, including prevalence of complications. Patients with hypokalemia detected by chance blood test should have gene tests performed. Patients with GS need attention for developing extrarenal complications, such as short stature, febrile convulsion, thyroid dysfunction, epilepsy, or QT prolongation. It was also revealed for the first time that hypomagnesemia was not severe in some variants in .
吉特曼综合征（GS）是一种表现为失盐的肾小管病。GS病例大多通过偶然的血液检查确诊。除此之外，一些病例也通过与低钾血症和/或低镁血症相关的手足抽搐症状或身材矮小得以诊断。至于并发症，甲状腺功能障碍和身材矮小是已知的，但这些并发症的发病率尚未阐明。此外，GS中尚未发现基因型与表型的相关性。
我们研究了185例经基因证实的具有纯合或复合杂合变体的GS病例的临床特征及基因型与表型的相关性。
在我们的队列中，诊断机会来自偶然的血液检查（54.7%）、手足抽搐（32.6%）或身材矮小（7.2%）。关于并发症，16.3%有身材矮小，13.7%曾有高热惊厥，4.3%有甲状腺功能障碍，2.5%被诊断为癫痫。有1例检测到QT间期延长。在29例身材矮小的病例中，10例被诊断为生长激素（GH）缺乏并开始了GH替代治疗。有趣的是，在日本人群中，携带p.Arg642Cys和/或p.Leu858His变体的病例与不携带这些变体的病例之间血清镁水平存在强相关性（1.76mg/dl对1.43mg/dl，P<0.001），而这些变体是突变热点。
本研究首次揭示了日本人群中经基因证实的GS病例的临床特征，包括并发症的发生率。通过偶然血液检查发现低钾血症的患者应进行基因检测。GS患者需要关注肾外并发症的发生，如身材矮小、高热惊厥、甲状腺功能障碍、癫痫或QT间期延长。本研究还首次揭示，在某些特定变体中低镁血症并不严重。
