Balkan Journal of Medical Genetics

TWO BROTHERS FROM MACEDONIA WITH GITELMAN SYNDROME
Janchevska A, Tasic V, Jordanova O, Gucev Z, Jenkins L, Jovanovska N, Plaseska – Karanfilska D, Ashton E, Bockenhauer D
*Corresponding Author: Ass. Prof. Dr. Aleksandra Janchevska, University Children’s hospital, Skopje, Rep. of N. Macedonia; Email: dr.sasha1969@yahoo.com
page: 69

INTRODUCTION

Gitelman syndrome (#MIM 263800, GS) is a rare and autosomal recessive renal disorder, characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria [1]. It was first described in 1966 by Gitelman, Graham and Welt [2], and the underlying gene SLC12A3 was identified in 1996 [3]. The prevalence has been variably estimated, but it is typically around 1 in 40,000 among Caucasians [4]. Yet, based on the frequency of pathogenic variants, the actual prevalence maybe as high as 1:1250, suggesting that many patients may go undiagnosed [5]. Although presentation in the neonatal period has been reported, only a few patients are actually diagnosed because of symptoms in childhood [6]. Most patients present with symptoms in adolescence or adulthood. The spectrum of clinical manifestations is wide, from asymptomatic to severe forms. Salt craving, episodes of muscle weakness or symptoms of neuromuscular irritability, fatigue, excessive thirst, growth delay or delayed puberty and abdominal pain have all been reported [7]. There is also variability in the biochemical manifestations [8]. Several other disorders, especially Bartter syndrome type 3, have similar symptoms [8]. Biallelic disease-causing variants in SLC12A3 have been found in the majority of patients with GS. This gene is located on the long arm of chromosome 16 (16q13) and contains 26 exons [3, 9]. In some patients, only a single heterozygous coding variant is identified, but with the advent of new sequencing technology, intronic variants on the other allele, copy number variants or complex genomic rearrangements may be found [10]. SLC12A3 encodes the 1030 amino-acid thiazidesensitive sodium chloride cotransporter (NCCT) protein (NM_000339.2; OMIM 600968) that mediates apical sodium-chloride uptake in the distal convoluted tubule (DCT) [11]. Here, we report on two preschool boys with clinical presentation of Gitelman syndrome, confirmed by mo- lecular analysis. They are, to the best of our knowledge, the first described and confirmed cases of GS in childhood in our country. Yet, given the frequency of the disorder around the world, the question arises, whether other cases have remained undiagnosed. We therefore present these patients to raise awareness of this disorder in the Republic of N. Macedonia.

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