Abstract
ContextGitelman 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.ObjectiveTo analyze the clinical and genetic characteristics and treatment of all members of 13 GS pedigrees.MethodsThirteen pedigrees (86 members, 17 GS patients) were enrolled. Symptoms and management, laboratory findings, and genotype–phenotype associations among all the members were analyzed.ResultsThe 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+, Mg2+, and 24-h urinary Ca2+ levels. Although blood pressure, serum K+ and Mg2+ 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 Mg2+ 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.ConclusionThe 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.
Highlights
Gitelman syndrome (GS, OMIM 263800), one of the most common hereditary disorders of potassium homeostasis, is characterized by hypokalemia, hypomagnesemia, and hypocalciuria without hypertension [1, 2]
We summarized and analyzed the genotype and phenotype associations of all the members from 13 GS pedigrees
We found that the 24-h sodium urine excretion was significantly higher in heterozygous individuals than in healthy controls, though there was no difference in blood pressure levels between them
Summary
Gitelman syndrome (GS, OMIM 263800), one of the most common hereditary disorders of potassium homeostasis, is characterized by hypokalemia, hypomagnesemia, and hypocalciuria without hypertension [1, 2]. In Asia, the prevalence of GS increases to an astonishing 10.3 per 10,000 people [5], and the prevalence of mutations may be as high as 3% [3]. Some researchers have analyzed the clinical and genetic characteristics in unrelated patients with GS. Follow-up study is imperative for in-depth research to seek out a better method for GS treatment and to prevent further exacerbation of the disease. We analyzed the clinical and genetic characteristics among all the members of 13 GS pedigrees, and continuous follow-up was performed for about 3 years to accumulate valuable data on the treatment of GS. Our research may assist in the understanding of phenotypic variability and provide useful insight into the characteristics of GS as well as therapeutic strategies for this disease
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