Janchevska A, Tasic V, Jordanova O, Gucev Z, Jenkins L, Jovanovska N, Plaseska-Karanfilska D, Ashton E, Bockenhauer D
University Children's hospital, Skopje, Rep. of N. Macedonia.
North East Thames Regional Genetic Laboratory, Great Ormond Street Hospital for children, London, UK.
Balkan J Med Genet. 2023 Jul 31;26(1):69-74. doi: 10.2478/bjmg-2023-0009. eCollection 2023 Jul.
Gitelman syndrome (GS) is a rare renal tubulopathy with an autosomal recessive mode of inheritance, caused by biallelic pathogenic variants in the gene. The clinical features may overlap with other disorders, such as Bartter syndrome type 3, HNF1B nephropathy or even mitochondrial disease, but can be distinguished by molecular genetic analysis. Here we report on two preschool brothers, who presented with a several months' history of episodes of carpopedal spasms and muscle aches. The biochemical analyses revealed hypokalemia and hypomagnesemia without metabolic alkalosis. A 24-h urine sample demonstrated hypocalciuria. The molecular analyses showed that both patients were heterozygous for 3 (likely) pathogenic variants in : c.1805_1806del; p. (Tyr602Cysfs*31), c.2660+1G>A and c.2944 A>T; p. (Ile982Phe). Analysis of the parents showed that the mother was heterozygous for the c.2944 A>T p.(Ile982Phe) variant, and the father carried the other 2 variants (c.1805_1806del and c.2660+1G>A). Herein we present two children in a family from N. Macedonia with clinical manifestations and electrolyte imbalances suggestive of GS. The results of the tubulopathy next generation sequencing (NGS) panel confirmed the diagnosis. The boys are treated with a high salt diet and oral potassium and magnesium supplements.
吉特曼综合征（GS）是一种罕见的肾小管病，呈常染色体隐性遗传模式，由该基因的双等位基因致病性变异引起。其临床特征可能与其他疾病重叠，如3型巴特综合征、HNF1B肾病甚至线粒体疾病，但可通过分子遗传学分析加以区分。在此，我们报告两名学龄前兄弟，他们有几个月的手足痉挛和肌肉疼痛发作史。生化分析显示低钾血症和低镁血症，无代谢性碱中毒。24小时尿液样本显示尿钙减少。分子分析表明，两名患者在该基因中均为3个（可能）致病性变异的杂合子：c.1805_1806del；p.（Tyr602Cysfs*31）、c.2660+1G>A和c.2944 A>T；p.（Ile982Phe）。对父母的分析显示，母亲为c.2944 A>T p.（Ile982Phe）变异的杂合子，父亲携带另外2个变异（c.1805_1806del和c.2660+1G>A）。在此，我们展示了来自北马其顿一个家庭的两名儿童，其临床表现和电解质失衡提示为吉特曼综合征。肾小管病下一代测序（NGS） panel的结果证实了诊断。这两名男孩接受高盐饮食以及口服钾和镁补充剂治疗。
