Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome

CONTEXT: Gitelman syndrome (GS) is clinically heterogeneous. The genotype and phenotype correlation has not been well established. Though the long-term prognosis is considered to be favorable, hypokalemia is difficult to cure. OBJECTIVE: To analyze the clinical and genetic characteristics and treatment of all members of 13 GS pedigrees. METHODS: Thirteen pedigrees (86 members, 17 GS patients) were enrolled. Symptoms and management, laboratory findings, and genotype–phenotype associations among all the members were analyzed. RESULTS: The average ages at onset and diagnosis were 27.6 ± 10.2 years and 37.9 ± 11.6 years, respectively. Males were an average of 10 years younger and exhibited more profound hypokalemia than females. Eighteen mutations were detected. Two novel mutations (p.W939X, p.G212S) were predicted to be pathogenic by bioinformatic analysis. GS patients exhibited the lowest blood pressure, serum K(+), Mg(2+), and 24-h urinary Ca(2+) levels. Although blood pressure, serum K(+) and Mg(2+) levels were normal in heterozygous carriers, 24-h urinary Na(+) excretion was significantly increased. During follow-up, only 41.2% of patients reached a normal serum K(+) level. Over 80% of patients achieved a normal Mg(2+) level. Patients were taking 2–3 medications at higher doses than usual prescription to stabilize their K(+) levels. Six patients were taking spironolactone simultaneously, but no significant elevation in the serum K(+) level was observed. CONCLUSION: The phenotypic variability of GS and therapeutic strategies deserve further research to improve GS diagnosis and prognosis. Even heterozygous carriers exhibited increased 24-h Na(+) urine excretion, which may make them more susceptible to diuretic-induced hypokalemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40618-018-0966-1) contains supplementary material, which is available to authorized users.