Congenital isolated hypoaldosteronism is associated with salt-losing and failure to thrive in infancy. The terminal stages of aldosterone (A) synthesis require two mixed function oxidases: CMO-I and CMO-II. Corticosterone (B) is converted to a labile intermediate by CMO-I which is then converted to A by CMO-II. Absence of CMO-II activity results in low circulating levels of A and accumulation of 18-hydroxycorticosterone (18-OHB) generated from the labile intermediate. The normal ratio of 180HB/A in both urine and plasma is 2. Ratios in infants with CMO-II deficiency have been >15. We now report an infant with CMO-I deficiency
A 5 week female infant presented with failure to thrive and hyperkalemia (10 mEq/L),hyponatremia (110),hyperrenninemia (804 ng/ml/hr) and hypoaldosteronemia (2.7 ng/dl). B was elevated (1128,1013 ng/dl).Desoxycorticosterone (DOC) and 18-hydroxy-DOC levels were mildly elevated (25 and 21 ng/dl respectively).18-OHB values were in the normal range (25,22 ng/dl).Plasma ratios of 18-OHB/A were 2.5,3.1. Urinary ratios of the metabolites of these compounds ranged between 2.3 and 2.6. ACTH did not increase A levels significantly (6.7→8.9), but B increased three-fold (473→1559). 18-OHB levels increased only to the high normal range (22→47). The clinical and biochemical abnormalities readily corrected with mineralocorticoid and salt. Low A levels in the presence of normal 18-OHB/A ratios in the salt depleted state constitute evidence for decreased CMO-I activity.
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Shulman, D., Vargas, A., Prebis, J. et al. CONGENITAL HYPOALDOSTERONISM DUE TO DEFICIENCY OF CORTICOSTERONE METHYL OXIDASE I (CMO-I) ACTIVITY. Pediatr Res 18, 177 (1984). https://doi.org/10.1203/00006450-198404001-00505