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Abstract: PO1662

A Delayed Diagnosis of Gordon Syndrome: Better Late Than Never!

Session Information

Category: Trainee Case Report

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Sambharia, Meenakshi, University of Iowa, Iowa City, Iowa, United States
  • Thomas, Christie P., University of Iowa, Iowa City, Iowa, United States
  • Noureddine, Lama A., University of Iowa, Iowa City, Iowa, United States
Introduction

Gordon syndrome, also known as Pseudohypoaldosteronism Type II (PHA-II) or Familial Hyperkalemic Hypertension (FHH), is a rare Mendelian syndrome causing hypertension(HTN), hyperkalemia and non-anion gap metabolic acidosis. Genes responsible are the with- no-lysine kinase 1 and 4 (WNK1/WNK4), kelch-like 3 (KLHL3) and cullin 3 (CUL3). WNK1/WNK4 are expressed in the DCT, connecting tubule and collecting duct. WNK4 reduces cell surface expression of the thiazide sensitive Na-Cl co-transporter (NCCT) and the potassium channel, ROMK. WNK1 prevents WNK4 from interacting with NCCT. KLHL3 and CUL3 are part of a ubiquitin ligase complex that targets WNK4 for degradation. While FHH from WNK1, WNK4 and CUL3 have an autosomal dominant (AD) mode of inheritance, disease from KLHL3 can be autosomal recessive (AR) or AD. AR disease presents at an earlier age with severe hypertension and hyperkalemia.

Case Description

A 56-year-old Caucasian male with history of recurrent atrial fibrillation with multiple cardioversions was referred to renal clinic for evaluation of chronic hyperkalemia. Upon presentation, he had been on furosemide 40mg and sodium polystyrene sulfonate (SPS) 30mg daily for the last 6 years for K+ values as high as 7 mEq/L with normal renal function. Initially the hyperkalemia was attributed to Type IV RTA from heavy NSAID use. Renin and aldosterone levels were low at 0.1ng/ml/hr and 6.1ng/dl respectively. He was suspected to have Gordon syndrome and was referred for genetic counseling and testing. He had a family history of HTN in his mother, father and multiple brothers. His daughter, in her 30s, also had a history of long-standing hyperkalemia. Genetic testing identified a heterozygous likely pathogenic missense variant in KLHL3: NM_001257194:c.1487G>A,p.Arg496His. Based on prior reports and within this clinical context, this variant confirmed a diagnosis of AD FHH. Furosemide was switched to low hydrochlorothiazide, SPS was discontinued and hyperkalemia resolved.

Discussion

Hypertension with hyperkalemia should prompt evaluation for Gordon syndrome. Thiazides are the treatment of choice. When suspected, genetic testing confirms diagnosis, prompting disease-guided therapy and preventing life-threatening consequences.