Resolution of Metabolic Abnormalities During Pregnancy in a Patient with Gordon Syndrome and KLHL3 Mutation

ABSTRACT Objective: To report the case of a female patient who was diagnosed with Gordon syndrome causing chronic hyperkalemia with normal renal function and clinical implications during pregnancy. Methods: The pertinent clinical features, laboratory data, and clinical course of the patient, both during and after pregnancy, are reported along with a brief literature review. Results: The patient was a 28-year-old female who had a history of multiple visits to the emergency department due to muscle twitching and generalized weakness since 2007. During these visits, she was found to have hyperkalemia without apparent cause. She was not on any culprit medications. Laboratory work-up showed hyperkalemia ranging between 5.5 to 6.4 mmol/L and hyperchloremic metabolic acidosis but normal renal function. Adrenal insufficiency was ruled out with normal morning cortisol and appropriate cortisol response to a stimulation test with 250 μg adrenocorticotropic hormone. Renin was low at 2.5 ng/L (normal range is 3.2 to 59.3 ng/L), aldosterone was inappropriately normal at 250 pmol/L (normal range is 103 to 1,197 pmol/L). The fludrocortisone challenge test failed to decrease her potassium levels. Genetic testing confirmed mutation in the kelch-like family member 3 gene (c.254A>T, p.Glu85Val) confirming the diagnosis of Gordon syndrome. Hydrochlorothiazide was initiated which reversed her biochemical abnormalities. She became pregnant, and her potassium levels normalized throughout pregnancy without the need for thiazides. Her blood pressure remained normal. Her pregnancy was uneventful. Following delivery, her potassium levels increased requiring re-initiation of thiazides. Conclusion: We report the seventh case describing the clinical course of Gordon syndrome during pregnancy and postpartum. All other cases reported show continued need for treatment during pregnancy whereas our patient had resolution of the metabolic defects. Abbreviations: CUL3 cullin 3 gene GS Gordon syndrome HCTZ hydrochlorothiazide KLHL3 kelch-like family member 3 gene NCC sodium-chloride cotransporter channel WNK with-no-lysine kinase