Normomagnesemic Gitelman syndrome presenting with recurrent abdominal pain and compound heterozygous SLC12A3 variants: a case report

Gitelman syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy caused biallelic disease-associated variants in SLC12A3 , which encodes the thiazide-sensitive Na + -Cl - cotransporter. Typical features include hypokalemia, metabolic alkalosis, hypomagnesemia, hypocalciuria, normal or low blood pressure, and activation of the renin–angiotensin–aldosterone system. A 17-year-old Chinese girl presented with recurrent periumbilical pain and hypokalemia without an identifiable precipitating factor. Electrolyte results before the current episode were reportedly not obviously abnormal; during the episode, an outpatient test showed potassium 2.77 mmol/L two weeks before admission. Whole-exome sequencing identified two heterozygous SLC12A3 missense variants, c·3026 G > A (p.Arg1009Gln) and c·1084 G > A (p.Gly362Ser). Targeted Sanger sequencing showed maternal transmission of p.Arg1009Gln and paternal transmission of p.Gly362Ser, establishing an in-trans configuration. According to the supplied laboratory ACMG/AMP interpretation, the variants were classified as pathogenic and likely pathogenic, respectively; public ClinVar records classify both as pathogenic. The genetic findings supported GS despite a normal serum magnesium measurement and no documented prominent neuromuscular manifestations. During oral potassium chloride treatment, abdominal pain improved substantially and serum potassium increased from 2.86 mmol/L at admission to 3.72 mmol/L at one month. This case highlights that Gitelman syndrome can present with isolated recurrent abdominal pain and normomagnesemia, mimicking a functional gastrointestinal disorder. Unexplained hypokalemia with renal potassium wasting should prompt early genetic screening for SLC12A3 mutations, even when neuromuscular manifestations are absent. Further investigation into genotype–phenotype correlations for novel or rare missense variants is warranted to improve early diagnosis and management of this autosomal recessive tubulopathy.