Challenges in the Diagnosis and Management of a Paediatric Patient With Normotensive Pseudohypoaldosteronism Type IID

Pseudohypoaldosteronism type IID (PHA2D) is a rare genetic disorder caused by mutations in the KLHL3 gene, leading to increased activity of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the kidneys. This overactivity promotes excessive sodium and chloride reabsorption, resulting in hyperkalaemia, hyperchloremic metabolic acidosis, and suppressed renin/aldosterone levels, despite preserved renal function. We report the case of a nine-year-old boy presenting with chronic fatigue, muscle aches, and growth failure. Laboratory evaluation revealed severe hyperkalaemia and hyperchloremic metabolic acidosis with a normal glomerular filtration rate and persistent normotension. Due to an initial clinical suspicion of isolated mineralocorticoid deficiency, a diagnostic trial of fludrocortisone was initiated while awaiting definitive results. Although this trial improved biochemical markers, it was discontinued once suppressed renin and aldosterone levels pointed toward PHA2. Subsequent genetic testing identified a novel homozygous splice-site mutation in the KLHL3, confirming autosomal recessive PHA2D. Following confirmation of the diagnosis, treatment was transitioned to the disease-specific therapy, hydrochlorothiazide (0.5 mg/kg/day). While this regimen normalized serum potassium and acid-base status, it induced symptomatic hypotension. The dosage was ultimately titrated to an alternate-day, low-dose regimen (0.25 mg/kg), which successfully maintained metabolic stability while minimizing adverse effects. This case underscores that normotension in PHA2D may delay diagnosis and that standard thiazide dosing may precipitate hypotension in previously normotensive patients, necessitating highly individualized treatment strategies.