Looking beyond Entecavir to discover Gitelman Syndrome in a 50 year-old man.

BACKGROUND: Potassium (K+) is essential for cells functions and alterations of the normal plasmatic levels can be life-threatening. The kidney is crucial in maintaining K+ homeostasis, mainly by regulating its secretion in the urine. Hypokalemia is influenced by acid-base status and can be associated to both metabolic alkalosis or acidosis. In adults, drug-induced hypokalemia is the most common form, however, genetically undiagnosed conditions should always be investigated. CASE REPORT: We present the case of a 50-year old male patient with asthenia and hypokalemia treated with a Direct Acting Antiviral (DAA). Hypokalemia was ascribed to DAA therapy and potassium salt supplementation was started without improvement. Blood gas analysis revealed the presence of hypokalemic metabolic alkalosis. Since DAA-induced hypokalemia has been reported as secondary to proximal renal tubular acidosis(RTA), the role of entecavir was questioned. Urinalysis was negative for glycosuria and phosphaturia, while the presence of hypocalciuria raised the hypothesis of a Gilteman-like tubulopathy. Thus, a thiazide administration test was performed. Delta FeCl- failed to increase above 2.3% in all studied time points supporting the diagnosis of Gitelman Syndrome that was afterward confirmed by the genetic test, that showed the presence two in trans SLC12A3 mutations. CONCLUSION: This case report suggests that genetically determined tubulopathies can be underdiagnosed and should always be considered in the differential diagnosis of non-hypertensive, hypokalemic metabolic alkalosis.