Pseudohypoaldosteronism Type II

Abstract

Pseudohypoaldosteronism type I (PHAI) is sometimes dominantly inherited and is characterized by mutations causing a near-absence of mineralocorticoid receptors in the kidneys.1 This leads to salt-wasting and hyperkalemia, despite increased aldosterone levels. It starts in infancy but eases toward adulthood. There is also a recessive form2 of PHAI that is more severe, associated with loss of function mutations of epithelial sodium (Na+) channels (ENaC) in the late distal tubules (DTs), the connecting tubule and collecting ducts, and also in other tissues expressing the ENaC. It starts in the newborn, with life-threatening salt-wasting and hyperkalemia. Salt supplements of ≤45 g/d are required indefinitely, together with control of hyperkalemia. More than 100 cases of these forms of PHAI have by now been described. PHAII is also inherited, but can be sporadic, in which hyperkalemia despite a normal glomerular filtration rate is the cardinal presenting feature. There is also acidosis and a low plasma renin level and a high incidence of hypertension. Plasma aldosterone levels are low to mildly but inadequately increased. This disease was named PHAII by Schambelan et al,3 but it has also been known as Familial Hyperkalemia and Hypertension, Gordon Syndrome, and Chloride Shunt Syndrome. The first case was described in 1964 by Paver and Pauline.4 In 1968, their patient, a white man aged 18 years, came under my care. He had a plasma potassium (K+) of 8.2 mmol/L, a normal glomerular filtration rate, acidosis, and a blood pressure of 180/120 mm Hg.5 Although Paver and Pauline4 found that he had an extreme cold pressor response, we did not find it so in 1968, but meanwhile it may have been affected by treatment. Renal biopsy was normal. Plasma renin level was low, and plasma aldosterone was low normal. A 4-day balance study …