Case report: Two novel compound heterozygous variant of SLC12A3 gene in a gitelman syndrome family and literature review

• Published in: Frontiers in genetics 2024-07, Vol.15, p.1391015
• Main Authors: Ji, Xiaochen, Zhao, Nan, Liu, Haixia, Wu, Yutong, Liu, Lichao
• Format: Article
• Language: English
• Subjects: diabetes mellitus; Genetics; gitelman syndrome; hypokalaemia; hyponatraemia; SGLT2 inhibitors
• ISSN: 1664-8021; 1664-8021
• DOI: 10.3389/fgene.2024.1391015

A 36-year-old unmarried male chef was incidentally diagnosed with hypokalemia during an evaluation for an acute perianal abscess. Despite potassium supplementation, he developed progressive weakness in his lower limbs, culminating in an inability to stand. Investigations confirmed severe hypokalemia, metabolic alkalosis, hypomagnesemia, secondary hyperaldosteronism, and low urinary calcium excretion, with normotension. The patient's long-standing stunted growth and lean physique since childhood were noted. Biochemical assays further identified type 2 diabetes mellitus and metabolic syndrome. Genetic analysis revealed three heterozygous mutations (M1: c.421G>A: .G141R, M2: c.509T>A: .L170Q, and M3: c.704C>A: .T235K), compound heterozygo us and derived from both parents, with M1 and M3 reported here for the first time. Treatment with spironolactone and oral potassium chloride stabilized his potassium levels. Following the administration of SGLT2 inhibitors in patients receiving hypoglycemic therapy, we observed a mild decrease in serum sodium levels. This case highlights the criticality of vigilant metabolic surveillance in Gitelman syndrome and advises prudence with SGLT2 inhibitors in those with concurrent type 2 diabetes, given the risk of potentially aggravate sodium loss.