A novel SLC12A3 homozygous c2039delG mutation in Gitelman syndrome with hypocalcemia

Abstract

Background: Gitelman syndrome (GS) is a rare autosomal recessive renal tubular disease, caused by mutations in the SLC12A3 gene, which encodes the renal thiazide-sensitive Na/Cl cotransporter (NCCT) in the distal renal tubule.

Case presentation: A 23-year-old woman was admitted with limb numbness, recurrent tetany and palpitation. Laboratory tests showed hypokalemic alkalosis, hypomagnesemia, hypocalcemia and secondary hyperaldosteronism, as well as hypocalciuria and transient decreased PTH. Next-generation sequencing detected a novel homozygous mutations c.2039delG in the SLC12A3 gene, and her father and children were all heterozygous carriers.

Conclusion: We reported a case of GS with a novel homozygous frame-shift mutation of SLC12A3, and reviewed recent literatures about diagnosis, differential diagnosis and treatments. Hypocalcemia in Gitelman syndrome is rare, and may be related to inhibited PTH secretion induced by hypomagnesemia.

Keywords: Gitelman syndrome; Hypocalcemia; SLC12A3 gene mutation.

Fig. 1

Pedigree analysis

Fig. 2

Sequences of the patient, her children and her father. The above sequence column is the reference sequence, next are the sequence of the patient and her son, daughter, father, respectively. The columns below tested sequences are subtracted results of tested sequence and reference sequence, which show homozygous c.2039delG of the patient and heterozygous mutation of her children and father)