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

DISCUSSION

Gitelman syndrome is an inherited renal tubulopathy [11, 14] typically diagnosed in adolescence or adulthood. There are only a few reports of it being diagnosed before the 6th year of age [4, 6, 15, 16, 17]. The non-specificity of the symptoms, and their mild presentation are perhaps the reason for the late recognition of the syndrome. Indeed, many patients may have no apparent symptoms and are identified when a blood test is obtained for unrelated reasons. Thus, hypokalemic metabolic alkalosis with hypomagnesaemia should prompt the suspicion of this diagnosis [18, 19, 20, 21, 22] which should be then confirmed by genetic testing. A Gitelman-like phenotype can also be acquired: for instance, chronic diarrhea [23], vomiting, bulimia, anorexia, long-term abuse of laxatives or diuretics may mimic the symptoms of mild forms of GS. In 2011 Vargas et al. [24] reported 172 mutations in a large cohort of 448 GS patients, of which 59% were missense mutations detected by direct sequencing and in approximately 6%, large rearrangements were found by MLPA analysis. Glaudemans et al., 2012 [25], in a cohort of 163 patients with clinical signs of GS detected 114 mutations in the SLC12A3 gene by direct sequencing of which 31 were novel. No specific genotype-phenotype correlations have been reported. In 2018, Ashton et al. [12], identified 269 variants in 27 genes in 410 patients by using a specially designed kit for targeted amplification of 37 known tubulopathy disease genes. The emergence of simultaneous sequencing of a panel of multiple genes has become an increasingly used method. They genetically confirmed 63 GS patients with childhood-onset symptoms by the panel sequencing. This comprehensive method distinguished the overlapping phenotypes and enabled an accurate diagnosis. A few isolated cases of GS patients have been associated with other rare conditions such as nephrotic syndrome, parathyroid adenoma or growth hormone deficiency, which presumably just reflects the frequency of the syndrome, as these symptoms are likely unrelated [26, 27, 28]. The two brothers with GS fulfilled already established biochemical diagnostic criteria by the KDIGO consensus report [17] and the tubulopathy panel sequencing followed by the Sanger sequencing confirmed the diagnosis. The treatment with a high salt diet and oral potassium and magnesium supplements followed the recommendations from the consensus guidelines. It has helped to maintain the biochemical parameters almost within reference range and reduced the frequency of the symptoms to a minimum. Some GS patients with severe symptoms have been treated with intravenous potassium and/or magnesium supplements and/or potassium-sparing diuretics, pain medications, renin angiotensin system blockers and nonsteroidal anti-inflammatory drugs [17, 29, 30, 31]. The efficacy of these treatments remains to be established. The frequency and severity of symptoms in patients with GS is variable, but the majority of them have a good prognosis although, some cases may develop chronic renal insufficiency [31] or cardiac arrhythmias [1, 32].

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