Familial Pseudohypoaldosteronism

Abstract

The clinical course of two siblings with a severe form of pseudohypoaldosteronism was followed over a period of seven and five years respectively. Both children persistently had a high sodium-potassium excretion ratio in the urine, sweat, saliva, and stools as well as high serum concentrations of aldosterone and renin and an increased urinary excretion of tetrahydroaldosterone. Despite sustained treatment with sodium chloride (10-40 mmol/kg/d) and cation exchange resin (sodium polystyrole sulfonate 0.5-2 g/kg/d) they repeatedly developed episodes of salt wasting and hyperkalemia which occurred mainly during uncomplicated respiratory tract infections. Aldosterone receptor characteristics were studied in the cytosol of the rectal mucosa at ages 2.5 years and 6 months respectively. Compared to age matched controls there was a decreased affinity for aldosterone at the low affinity binding site. Among the members of the family, the father and one of his sisters had high concentrations of sodium in the sweat and an increased urinary excretion of tetrahydroaldosterone.

Renal Genetic Disorders Related to K+ and Mg2+

“…Finally, it may be possible to discern relatively mild symptoms or findings in the heterozygote parents and relatives of children affected with the recessive form of the syndrome. Two severely affected sibs with high Na + /K + excretion ratios in urine, sweat, saliva, and stool were described who had salt wasting and severe hyperkalemia during upper respiratory infections (136). Of note, the father and his sister were not symptomatic but had high sweat Na + levels and chronically increased aldosterone secretion, as measured by increased urinary tetrahydro-aldosterone levels, perhaps manifesting the previously undetected heterozygotic carrier state of the disorder (136).…”

Erythrocyte Na+,K+‐ATPase and nasal potential in pseudohypoaldosteronism*

“…Pseudohypoaldosteronism type 1 (PHA1) is a rare disease characterized by salt‐wasting, severe dehydration, hyponatraemia and hyperkalaemia, metabolic acidosis and failure to thrive presenting early during the neonatal period (Cheek & Perry, 1958; Dillon et al ., 1980; Popow et al ., 1988). Plasma aldosterone concentration and renin activity are elevated and a resistance to mineralocorticoids is observed.…”

Type I Pseudohypoaldosteronism Includes Two Clinically and Genetically Distinct Entities with either Renal or Multiple Target Organ Defects

“…Serum electrolyte levels also normalize with increasing age (4), but aldosterone concentrations in both symptomatic and asymptomatic patients may remain elevated until adulthood (5-7, 15, 16). In a minority of patients with type I PHA, responsiveness to aldosterone is impaired in multiple organs including salivary and sweat glands, renal tubules, and colonic mucosal cells (12,(17)(18)(19)(20). These patients exhibit a more protracted course of the disease with recurrent life-threatening episodes of salt losing.…”