Pseudohypoaldosteronism type II (PHAII), also known as Gordon syndrome, is a rare Mendelian disorder characterized by hypertension, hyperkalemia, hyperchloremic metabolic acidosis, and preserved renal function. Pathogenic variants in four genes—WNK1, WNK4, KLHL3, and CUL3—have been implicated, with KLHL3 mutations reported in both autosomal dominant and recessive inheritance patterns. The clinical significance of hyperkalemia-related cardiac arrhythmias in PHAII remains incompletely defined. We aimed to describe the clinical features of the first Taiwanese family with a KLHL3 mutation and to evaluate the potential association between hyperkalemia and arrhythmic events.

A 47-year-old man from southern Taiwan was evaluated for long-standing hypertension and recurrent hyperkalemia, despite preserved renal function. Blood pressure was well controlled with thiazide therapy; however, intermittent hyperkalemia persisted for at least six years, with serum potassium concentrations consistently ranging between 5.0 and 6.0 mmol/L. The family history was remarkable for two successive generations in which several members required pacemaker implantation for clinically significant arrhythmias. Based on the clinical phenotype and hereditary background, comprehensive biochemical and endocrine assessments, together with arterial blood gas analysis, were undertaken. In view of a suspected inherited disorder, including renal tubulopathy or late-onset congenital adrenal hyperplasia, whole-genome sequencing (WGS) was performed to identify potential pathogenic variants.

Biochemical evaluation demonstrated a transtubular potassium gradient (TTKG) of 6, suppressed plasma renin at 0.41 ng/ml/hr, plasma aldosterone of 19.9 ng/dl, serum potassium of 5.5 mmol/L, chloride of 109 mmol/L, and HbA1c of 6.4%. Electrocardiography revealed tall T waves in leads V2–V3. WGS identified a heterozygous KLHL3 missense variant consistent with PHAII and a heterozygous WFS1 missense variant, the latter potentially contributing to altered glucose metabolism. Subsequent genetic counseling confirmed that the patient’s elder brother and additional relatives exhibited similar clinical manifestations. Longitudinal follow-up is ongoing to clarify genotype–phenotype correlations.

We report the first Taiwanese family with KLHL3-associated PHAII, a hereditary disorder characterized by persistent hyperkalemia. Inadequate recognition and management of chronic hyperkalemia may have contributed to the high prevalence of arrhythmias requiring pacemaker implantation across multiple generations. These findings emphasize the importance of early diagnosis and prompt initiation of thiazide therapy to mitigate hyperkalemia and potentially reduce the risk of arrhythmic complications in younger affected individuals.