ESPN 51th Annual Meeting

ESPN 2018


 
Clinical characteristics in Gitelman syndrome and correlation between genotype and phenotype
JUNYA FUJIMURA 1 KANDAI NOZU 1 SHINYA ISHIKO 1 YUYA AOTO 1 CHINA NAGANO 1 NANA SAKAKIBARA 1 SHOGO MINAMIKAWA 1 TOMOHIKO YAMAMURA 1 KAZUMOTO IIJIMA 1

1- DEPARTMENT OF PEDIATRICS, KOBE UNIVERSITY GRADUATE SCHOOL OF MEDICINE, KOBE, JAPAN
 
Introduction:

Gitelman syndrome (GS) is a salt-losing tubulopathy characterized by hypokalemia and metabolic alkalosis. GS cases are usually diagnosed by tetanic symptoms associated with hypokalemia and/or hypomagnesemia. In addition, some cases are diagnosed by chance blood test. As for complications, thyroid dysfunction and short stature are known, but the incidence rates for these complications have not been revealed. In addition, no genotype-phenotype correlation has been identified in GS.

Material and methods:

We performed gene tests from November 2006 to September 2017 for clinically suspected GS cases and 185 cases were genetically diagnosed with GS. We examined the renal and extrarenal symptoms retrospectively using medical records. We analyzed clinical characteristics and genotype-phenotype correlation in genetically proven GS cases with homozygous or compound heterozygous variants in SLC12A3

Results:

The diagnostic opportunities were by chance blood tests (54.7%), tetany (32.6%) or short stature (7.2%) in our cohort. 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. 2.2% showed QT prolongation. Ten were diagnosed as growth hormone deficiency and growth hormone replacement therapy was started. Interestingly, there was a strong correlation in serum magnesium level between cases with p.Arg642Cys and/or p.Leu858His those are the mutational hot spots in the Japanese population and those patients without these variants. (1.76 vs 1.43 p<0.001).

Conclusions:

This study revealed the clinical characteristics in genetically proven GS cases including prevalence of complications. Cases with hypokalemia detected by chance blood test should be required gene tests. Cases with GS need attention for developing extrarenal complications such as thyroid dysfunction, short stature, epilepsy or QT prolongation. It was revealed for the first time that hypomagnesemia was not severe in some variants in SLC12A3.