Gitelman’s Syndrome with Vomiting Manifested by Severe Metabolic Alkalosis and Progressive Renal Insufficiency

Abstract

Gitelman's syndrome is an autosomal recessive salt-losing tubulopathy showing hypokalemic hypomagnesemic hypocalciuria with metabolic alkalosis and hyperreninemic hyperaldosteronism. This syndrome is caused by mutations in the SLC12A3 gene that encodes sodium-chloride cotransporter expressed at the apical membrane of renal distal convoluted tubule. Symptoms and renal outcomes of Gitelman's syndrome are, in general, mild and benign, and renal insufficiency from Gitelman's syndrome associated with long-standing hypokalemia and volume depletion is extremely rare. Herein, we report a 27-year-old male patient with Gitelman's syndrome who manifested renal failure, hypokalemia, severe metabolic alkalosis and altered mentality. About one year ago, the patient had been transferred to Seoul National University Hospital, because of unsolved hypokalemia, and was diagnosed as Gitelman's syndrome by clinical features and genetic analysis of the SLC12A3 gene. The patient carries a missense mutation at one allele of SLC12A3 gene (c.781C>T, p.Arg261Cys). His mother is also heterozygous for the same mutation and she had a history of hypokalemia. On this admission, the patient had recurrent bouts of vomiting induced by psychiatric eating disorder and showed severe volume depletion with hypotension, azotemia and metabolic alkalosis. Intense hydration therapy and emergency hemodialysis transiently improved his fluid-electrolyte imbalance and renal function. However, renal dysfunction progressively deteriorated despite the medical treatment. Our findings suggest that even in Gitelman's syndrome, constant monitoring for volume status and other comorbid conditions should be employed to prevent progressive renal injury.

The Importance of the Ionic Product for Water to Understand the Physiology of the Acid-Base Balance in Humans

“…Blockade of the Na + -K + -2Cl − cotransporter enhances sodium delivery to the collecting duct, where sodium is reabsorbed without chloride by the epithelial sodium channel (ENaC) [30, 31]. In addition, dysfunction of the Na + -K + -2Cl − cotransporter induces plasma volume contraction and subsequent activation of the renin-angiotensin-aldosterone (RAA) system that amplifies sodium reabsorption without chloride through the ENaC [30, 32, 33]. …”

“…This cotransporter is thiazide-sensitive, being inhibited by the administration of hydrochlorothiazide. Blockade of the Na + -Cl − cotransporter increases sodium delivery to the collecting duct where uptake of sodium takes place without chloride by the ENaC [30, 32]. …”

“…Hydrochlorothiazide use produces acquired inhibition of the Na + -Cl − cotransporter, while Gitelman syndrome due to mutations in the gene coding the transporter causes congenital dysfunction [30, 32]. …”

“…Mineralocorticoids such as aldosterone stimulate sodium reabsorption in the collecting duct through activation of the ENaC and therefore allow bicarbonate recovery and chloride waste in urine [35]. Metabolic alkalosis occurs in conditions associated with excess aldosterone activity, either autonomous secretion of aldosterone (primary aldosteronism) or secondary activation of the RAA system owing to renin-producing tumors, renal artery stenosis, and intravascular volume contraction of any etiology [30, 32, 33, 52]. …”

A causality dilemma: ARFID, malnutrition, psychosis, and hypomagnesemia

“…A literature search found a single case report of a patient with schizophrenia and Gitelman syndrome and a single case report of a patient with a purging eating disorder and Gitelman syndrome, demonstrating the rarity of these co‐occurrences (Pan, Mou, Li, Liu, & Hu, ; Lee, Lee, & Han, ). To our knowledge, this is the first reported case of a single patient with a co‐occurring eating disorder, psychosis, and Gitelman syndrome.…”