The role of SLC12A3 gene variant c.1964G > A in co-existing Gitelman syndrome and unilateral limb paralysis: a case report and literature review

We report a Gitelman syndrome (GS) pedigree from a Chinese family. The proband, a middle-aged man, presented with hypokalemia, hypomagnesemia, and unilateral limb paralysis. After a comprehensive evaluation, peripheral neuropathy and the cranial or spinal cord disorders were ruled out. Genetic testing identified a homozygous c.1964G > A variant in the SLC12A3 gene. Despite potassium and magnesium supplementation, the patient's clinical symptoms persisted. Additionally, 13 heterozygous family members, including his parents, showed no typical GS manifestations. However, the proband's two brothers, who also carried the same homozygous mutation and exhibited hypokalemia and hypomagnesemia, did not develop unilateral limb paralysis. This case suggests that the c.1964G > A variant may be associated with a severe GS phenotype, including unilateral limb paralysis. Clinicians should be aware of the diagnostic challenges and therapeutic limitations in managing GS, particularly in patients with severe manifestations. Genetic testing is essential for accurate diagnosis, and ongoing monitoring and symptomatic management are critical to improving the quality of life for affected individuals.