Genetic Analysis of Gitelman Syndrome: Co-existence with Hyperthyroidism in a Two-year-old Boy

A two-year-old boy visited the doctor for hypokalemia and metabolic alkalosis. Laboratory examination revealed that urinary potassium excretion and serum aldosterone level were increased, with hyperthyroidism and thyroid-related antibodies positive at the same time. Genetic testing showed that there was a complex heterozygous mutation in the SLC12A3 gene, c.1077C>G (p.N359K) and c.1567G>A (p.A523?); the final diagnosis was Gitelman syndrome and autoimmune hyperthyroidism.

Gitelman syndrome is an autosomal recessive genetic disease caused by the inactivation of mutation of the SLC12A3 gene. The onset age is more than 6 years old; it is mainly manifested as low blood potassium, low blood sodium, low blood chlorine, metabolic alkalosis, increased urine potassium and urine chlorine excretion, and low urine calcium. Autoimmune hyperthyroidism manifests due to autoimmune disorders. The highest incidence rate in children is of Graves' disease, followed by chronic lymphocytic thyroiditis.

Several cases of Gitelman syndrome with autoimmune hyperthyroidism have been reported, most of which were Asian adults, and the case we identified is the first reported case in children under 14 years with both Gitelman syndrome and autoimmune hyperthyroidism. At the same time, we carried out a high-precision clinical exosome analysis of the gene of this case and further explored the relationship between Gitelman syndrome and autoimmune hyperthyroidism from the perspective of the gene.This case suggests that even children under 6 years with hyperthyroidism and hypokalemia should be suspected of Gitelman syndrome to avoid misdiagnosis.