Pseudohypoaldosteronism type II: The Relevance of A Challenging Diagnosis

Pseudohypoaldosteronism type II (PHA II) is a rare genetic syndrome caused by mutations in the WNK1, WNK4, KLHL3 and CUL3 genes, leading to hypertension, hyperkalaemia, and hyperchloremic metabolic acidosis. Each mutation confers a different phenotype, with a large spectrum of clinical presentations, which can delay the diagnosis. We report a case of a 31-year-old female with hypertension. She had uncharacteristic facies, average height and no family history of hypertension or hyperkalaemia. Laboratory data showed hyperkalaemia, hyperchloremic metabolic acidosis, hypercalciuria and suppressed renin. Genetic testing revealed a c.478G>T, p.(Asp160Tyr) variant in the KLHL3 gene, in apparent homozygosity. Based on clinical history, laboratory findings, and genetic testing, a diagnosis of PHA II was made. This is a representative case of a mild PHA II phenotype, with a non-previously reported KLHL3 mutation, highlighting the importance of a high level of suspicion for PHA II.

We report a case of a young woman with PHA II caused by a novel variant in KLHL3, that highlights the importance of a high level of clinical suspicion for PHA II diagnosis in patients with milder phenotypes and without family history.PHA II should be considered in all patients with low-renin hypertension, hyperkalaemia, hyperchloremic metabolic acidosis and hypercalciuria, regardless of age, clinical features, or family history.Early diagnosis is extremely important because PHA II can be effectively treated with low dose thiazides, avoiding end organ damage onset.