Clinical analysis of children with Gitelman syndrome

Objective To explore the clinical manifestations, laboratory tests results, diagnostic and therapeutic methods of Gitelman syndrome (GS) children, to further improve the diagnosis and treatment of this disease. Methods From January 2017 to November 2018, a total of 9 cases (No.1-9) of GS children who were admitted to the Department of Endocrinology, Children′s Hospital, Capital Institute of Pediatrics were selected as study subjects. Their clinical data were collected retrospectively, and the clinical manifestations, genetic tests, treatments and outcomes, follow-up results were analyzed. This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013. Results ①Clinical manifestations and diagnostic results: 6 cases (No.1, 3, 4, 6, 8-9) showed infection or skeletal deformity, 2 cases (No.2, 7) showed short stature, 1 case (No.5) showed weakness of both lower limbs. Results biochemical examinations: all children had decreased blood K+ concentration, 8 cases (No.1-8) had low blood Mg2+ concentration, 7 cases (No.1, 3-8) had metabolic alkalosis, all children had increased 24 h urine K+ concentration, and β2 microglobulin the marker of renal tubular damage increased significantly in 5 cases (No.2, 4, 6, 8-9). Results of genetic test: 5 children (No.1, 6-9) underwent genetic test, and all of them had SLC12A3 gene mutation. No.1, 8 and 9 children had missense mutations. No.6 child had a shear mutation and a frameshift mutation, and the frameshift mutation caused the termination codon on mRNA to terminate amino acid in advance. No.7 child had a frameshift mutation. Frameshift mutation c. 578_582dupCCACC of No.6 child and missense mutations c. 1084G >A and c. 1613G>T of No.9 child were new mutations that have not been reported in the Human Gene Mutation Database (http: //www.hgmd.cf.ac.uk). ②Treatment outcomes: the 9 children with GS received potassium agent supplement, spironolactone [1-3 mg/(kg·d)] and potassium magnesium aspartate (1-2 tablets/times, 2-3 times/d). After treatment, blood K+ concentrations in 3 children (No. 5, 7-8) had not fully recovered to normal when discharged, but they were significantly higher than those at admission, and the blood K+ concentrations in other 6 children (No. 1-4, 6, 9) increased to normal. The blood Mg2+ concentrations in 9 children all basically returned to normal when discharged. ③Follow-up results: concentrations of blood K+ and Mg2+ in the 9 children were close to normal levels at 3 months after discharge, and growth rates of No.2 and 7 children with short stature showed improvement compared with that before treatment. Five children (No. 2, 4, 6, 8-9) with elevated renal tubular marker β2 microglobulin had no progressive exacerbation at the end of follow-up, and β2 microglobulin levels in 2 children (No. 4, 8) were basically returned to normal. Conclusions The clinical symptoms of GS children are not typical. If the biochemical test results of a child show low concentrations of blood K+ and Mg2+ , and increased concentration of urine K+ , then arterial blood gas analysis, detections of renin-angiotensin Ⅱ and aldosterone levels, and SLC12A3 gene mutations in genetic test are needed to confirmed the diagnosis of GS children. The treatment of this disease is mainly based on the combination of potassium agents, magnesium agents, and aldosterone antagonists and so on. Although it cannot be cured now, concentrations of blood K+ and Mg2+ of GS children can maintain normal, and its prognosis is good. Key words: Gitelman syndrome; Hypopotassemia; Hypomagnesemia; SLC12A3 gene; Frameshift mutation; Mutation, missense; Child