The Nature of the Defect in a Salt-Wasting Disorder in Jews of Iran12

Studies in 8 families of Iranian Jews revealed 12 patients with selective aldosterone deficiency due to a biosynthetic defect. There was a marked range in clinical severity which varied from acute salt-wasting crisis in infancy to an asymptomatic state in adults detectable only by biochemical screening. Manifestations of intermediate degrees of severity included unexplained short stature and postural hypotension. This clinical variability in the manifestations of aldosterone deficiency was not due entirely to quantitative differences in hormone secretion but also to a changing pattern of requirement throughout life in which deficiency during the first year of life had grave consequences while a similar degree of deficiency in the adult was well-tolerated, suggesting that the hormone was no longer essential. Most families came from a relatively isolated community in Isfahan with a high incidence of consanguinity and three were related. Aldosterone deficiency was due to an inborn error involving the terminal portion of the biosynthetic pathway and characterized by marked overproduction of glomerulosa zone 18-hydroxycorticosterone relative to aldosterone. The best diagnostic index was the excretory ratio of the major urinary metabolites of these steroids. This ratio, normally less than 3.0, was frequently greater than 100 in untreated patients with this defect. Plasma aldosterone was not a reliable index of the disorder since some patients achieved normal levels but at the expense of marked elevation in plasma renin activity and overproduction of precursors.