Two Japanese patients with gitelman syndrome

Abstract

Gitelman syndrome (GS) is a renal tubular disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria due to defective tubular reabsorption of magnesium and potassium. This disease is caused by mutations of the thiazide-sensitive Na-Cl cotransporter (NCCT) gene, SLC12A3. Manifestations of GS are heterogeneous, from asymptomatic to mild symptoms of cramps and easy fatigue, to tetany and paralysis. Polydipsia, polyuria, and nocturia are also frequent in GS patients. Here we describe two Japanese patients with GS followed as nocturnal enuresis. In the first patient, occasional muscle cramps, easy fatigue and headache led to the diagnosis of GS. The parents of this patient reported that he had been affected by polydipsia and polyuria, especially nocturnal enuresis from early childhood. The second patient was referred to our clinic because of muscular weakness and cramps. He had a past history of transient muscle weakness and muscle cramps. He had also suffered from nocturnal enuresis since 3 yr of age. Laboratory findings of these patients were consistent with those of GS. Sequencing analysis of the SLC12A3 gene from two patients showed four mutations, which were previously reported. In our two patients, their manifestations had been underestimated and the correct diagnosis was delayed. GS is generally likely to be benign, however signs of GS are found in early childhood. Especially, we must recognize that nocturnal enuresis is frequent in symptoms of GS.

Keywords: Gitelman syndrome; Na-Cl cotransporter (NCCT); SLC12A3 gene; nocturnal enuresis; polydipsia; polyuria.

Fig. 1

Sequencing analysis of Patient 1. (A) An arrow indicates the L623P mutation of exon 15. Double peaks of C and T were present in Patient 1(arrows). (B) A heterozygous two base (TT) deletion (nucleotide 2543 and 2544) was found. Note that after the deletion site, double peaks were shown (underline).

Fig. 2

Sequencing analysis of Patient 2. (A) G439S in exon 10. In Patient 2, double peaks of G and A were present (arrows). (B) S555L was identified in exon 13. C and T nucleotides (arrows) were present in the sequence of Patient 2.