ESPE Abstracts

Introduction: Pseudohypoaldosteronism type II (PHA II) is an extremely rare disorder characterized by low plasma renin and aldosterone when a normal renal function with hypertension, hyperkalemia, and hyperchloremic metabolic acidosis. PHA II is also known as familial hyperkalemic hypertension or Gordon’s syndrome and is an inherited autosomal dominant. PHA II could be caused by pathogenic variants of WNK1, WNK4, KLHL3, and CUL3.

Case: A 2-years-7-months-old boy had hyperkalemia, which was initially detected during the evaluation of elevated liver function tests. In our first evaluation, we detected hypertension, mild hyperchloremic metabolic acidosis, and hyperkalemia under the fludrocortisone treatment. He was born small for gestational age. The fludrocortisone was discontinued and endocrinological evaluation showed low plasma aldosterone concentration of 0,7 pg/ml (40-480 pg/mL) and low PRA: >0,52 ng/mL/hr (1-6,0 ng/mL/hr). After thiazide treatment, the patient's aldosterone concentration, PRA, and electrolyte levels were normalized with normal growth and development. A Next-Generation Sequencing unveiled that patient was heterozygous for novel variant c.1207-2A>C in CUL3 (NM_003590.4). No variant was detected in WNK1, WNK4, and KLHL3. Segregation analysis showed that c.1207-2A>C was de nova

Conclusions: PHA II should be evaluated in children presented with hypertension, and hyperkalemia. We predicted that the novel splice acceptor variant disrupts splicing. The c.1207-2A>C in CUL3 was not reported in the databases. De novo variant is classified as the "pathogenic", according to ACMG 2015 criteria with PVS1, PM2, and PS2. Aldosterone defects have a wide clinical and genetic spectrum and emergency treatment can be started without biochemical evaluation. Next-Generation Sequencing is effective in confirming the diagnosis.