Background: The children had normal 21-hydroxylase screening. An atypical form of congenital adrenal hyperplasia was initially suspected. The first child (female) had hyponatremia, hyperkalemia, elevated ACTH, and elevated androgens at birth. The second child (male) presented at 16 days with hyponatremia, hyperkalemia, normal cortisol, very elevated renin, low aldosterone, and elevated deoxycortisol. The third (female) and fourth (male) siblings had similar electrolyte abnormalities. The fifth child (male) was treated immediately at birth due to family history. The females had no ambiguous genitalia. The third child died of adrenal crisis associated with acute gastroenteritis. Mother had normal puberty and no history of salt wasting, electrolyte disturbance, or blood pressure abnormality. All three fathers were reportedly healthy.
Objective and hypotheses: The objective is to determine the etiology of congenital hypoaldosteronism. The hypothesis is that etiology is a rare genetic disorder transmitted by the mother.
Method: These children have been treated with daily mineralocorticoid therapy and as needed stress steroid therapy. Only the first child received daily cortisol replacement therapy but she was able to be weaned off. The oldest two siblings (different fathers) were evaluated by genetics. The mother and first, second, and fourth siblings (all different fathers) were evaluated by the National Institutes of Health.
Results: The oldest two siblings had unremarkable CYP11B1 genetic analysis. Mother and three of the siblings had chromosomal microarray testing with normal results. Mothers evaluation was not consistent with hypoaldosteronism or any adrenal insufficiency. Testing for CYP11B2 in one child is pending and if positive, the others may be tested.
Conclusion: An autosomal recessive disorder is extremely unlikely since all five children have the same mother but there are three different fathers. Differential diagnoses include de novo autosomal dominant or X-linked genetic disorders, or mitochondrial disease.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology