Heterozygous Mutations of The Gene for Kir 1.1 (ROMK) in Antenatal Bartter Syndrome Presenting with Transient Hyperkalemia, Evolving to a Benign Course

Bartter-like syndrome encompasses a set of inherited renal tubular disorders associated with hypokalemic metabolic alkalosis, renal salt wasting, hyperreninemic hyperaldosteronism, and normal blood pressure. Antenatal Bartter syndrome, a subtype of Bartter-like syndrome, is characterized by polyhydramnios, premature delivery, life-threatening episodes of fever and dehydration during the early weeks of life, growth retardation, hypercalciuria, and early-onset nephrocalcinosis. Mutations in the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and ATP-sensitive inwardly rectifying potassium channel (ROMK) of the thick ascending limb of Henle's loop have been identified in the antenatal Bartter syndrome. We report the identification of two heterozygous mutations of the gene for Kir 1.1 (ROMK) from an antenatal Bartter syndrome patient who presented at birth with mild salt wasting and a biochemical findings that mimicked primary peudohypoaldosteronism type 1, such as hyperkalemia and hyponatremia, and evolved to a relatively benign course. We have identified amino acid exchanges Arg338Stop and Met357Thr in the gene exon 5 for ROMK by PCR and direct sequencing. Both mutations alter the C-terminus of the ROMK protein, and can affect channel function.

Attenuated Renal Excretion in Response to Thiazide Diuretics in Gitelman's Syndrome: A Case Report

Gitelman's syndrome is a variant of Bartter's syndrome characterized by hypocalciuria and hypomagnesemia. The administration of thiazide diuretics may induce a subnormal increase of urinary Na+ and Cl- excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less Na+ and Cl- than normal is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Specific mutations of NaCl cotransporter, coupled with mutant NaCl cotransporter expression studies clearly demonstrated that many of the characteristics of individuals with Gitelman's syndrome are explained by lack of function of NaCl cotransporter. We recently diagnosed a patient with Gitelman's syndrome by performing the thiazide and furosemide tests, and it is suggested that the clearance studies by diuretic administration may be of diagnostic help in Gitelman's syndrome.

Gitelman′s syndrome (report of 2 cases) / 中华内分泌代谢杂志

Objective To study the clinical characteristics of Gitelman′s syndrome, and the differentiation of Gitelman′s syndrome from Bartter′s syndrome. Methods Clinical data of 2 patients diagnosed as Gitelman′s syndrome were retrospectively analysed. Results The symptoms of both patients appeared at adult age, their main manifestation included hypokalaemic alkalosis, hyperreninemia and juxtaglomerular apparatus hyperplasia with normal blood pressure, hypocalciuria and hypomagnesemia, then the diagnosis of Gitelman′s syndrome was established. Potassium and magnesium supplementation ameliorated one patient′s symptom. Another patient treated with indomethacin, serum potassium was recovered to normal level. Conclusion Gitelman′s syndrome and Bartter′s syndrome appear to be similar in the pathogenesis, clinical manifestation and prognosis, but still show some differences, Gitelman′s syndrome should be carefully differentiated from Bartter′s syndrome.