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Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome.

ABSTRACT: 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+, 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. 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.

SUBMITTER: Zhong F

PROVIDER: S-EPMC6531408 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome.

Zhong F F Ying H H Jia W W Zhou X X Zhang H H Guan Q Q Xu J J Fang L L Zhao J J Xu C C

Journal of endocrinological investigation 20181110 6

<h4>Context</h4>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.<h4>Objective</h4>To analyze the clinical and genetic characteristics and treatment of all members of 13 GS pedigrees.<h4>Methods</h4>Thirteen pedigrees (86 members, 17 GS patients) were enrolled. Symptoms and management, laboratory findings, and genotype-phenotype a ...[more]

PMID: 30413979

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Project description:Gitelman syndrome (GS), also referred to as familial hypokalemia-hypomagnesemia, is characterized by hypokalemic metabolic alkalosis in combination with significant hypomagnesemia and low urinary calcium excretion. The prevalence is estimated at approximately 1:40,000 and accordingly, the prevalence of heterozygotes is approximately 1% in Caucasian populations, making it one of the most frequent inherited renal tubular disorders. In the majority of cases, symptoms do not appear before the age of six years and the disease is usually diagnosed during adolescence or adulthood. Transient periods of muscle weakness and tetany, sometimes accompanied by abdominal pain, vomiting and fever are often seen in GS patients. Paresthesias, especially in the face, frequently occur. Remarkably, some patients are completely asymptomatic except for the appearance at adult age of chondrocalcinosis that causes swelling, local heat, and tenderness over the affected joints. Blood pressure is lower than that in the general population. Sudden cardiac arrest has been reported occasionally. In general, growth is normal but can be delayed in those GS patients with severe hypokalemia and hypomagnesemia.GS is transmitted as an autosomal recessive trait. Mutations in the solute carrier family12, member 3 gene, SLC12A3, which encodes the thiazide-sensitive NaCl cotransporter (NCC), are found in the majority of GS patients. At present, more than 140 different NCC mutations throughout the whole protein have been identified. In a small minority of GS patients, mutations in the CLCNKB gene, encoding the chloride channel ClC-Kb have been identified.Diagnosis is based on the clinical symptoms and biochemical abnormalities (hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria). Bartter syndrome (especially type III) is the most important genetic disorder to consider in the differential diagnosis of GS. Genetic counseling is important. Antenatal diagnosis for GS is technically feasible but not advised because of the good prognosis in the majority of patients.Most asymptomatic patients with GS remain untreated and undergo ambulatory monitoring, once a year, generally by nephrologists. Lifelong supplementation of magnesium (magnesium-oxide and magnesium-sulfate) is recommended. Cardiac work-up should be offered to screen for risk factors of cardiac arrhythmias. All GS patients are encouraged to maintain a high-sodium and high potassium diet. In general, the long-term prognosis of GS is excellent.

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Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome.

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Characteristics and Follow-Up of 13 pedigrees with Gitelman syndrome.

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