Hypokalemia, hypomagnesemia, hypocalciuria, and recurrent tetany: Gitelman syndrome in a Chinese pedigree and literature review

Abstract

Gitelman syndrome is an autosomal recessive disease mostly associated with loss-of-function mutations of the SLC12A3 gene and featured by clinical hypokalemia, hypomagnesemia, hypocalciuria, and histologically hypertrophy of the juxtaglomerular apparatus. A novel homozygous mutation (p.Arg399Pro) at the extracellular domain of SLC12A3 was found and correlated with the severe clinical manifestations.

Keywords: Gitelman syndrome; SLC12A3; phenotype–genotype relation; review.

Figure 1

Germline mutation in the pedigree. (A) Electropherogram of the proband revealing a homozygous c.G1196C point mutation. (B) Prediction of three‐dimensional structure of the wild‐type (left) and mutant (right) SLC12A3 protein. Yellow arrows show substitution of the hydrophilic amino acid arginine at codon 399 by a hydrophobic amino acid proline at the extracellular region of SLC12A3 protein. (C) Pedigree of the GS family.

Figure 2

Renal biopsy of the case presenting with Gitelman syndrome. (A) Light microscopic examination showed hypertrophy of juxtaglomerular apparatus (more than 50% of glomeruli involved) with proliferation of extraglomerular mesangial cell. The morphology of glomeruli is almost normal. (B) Electron microscopy revealed proliferation of extraglomerular mesangial cells. (C, D) Numerous secretive granules in the cytoplasm of this extraglomerular mesangial cell.

Figure 3

Associations of serum potassium with age at onset (panel on the left) and serum magnesium (panel on the right). The sizes of bubbles represent the sample sizes of different studies.