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Type 1 aldosterone synthase deficiency presenting in a middle-aged man
K M Kayes-Wandover1, R E Schindler, H C Taylor
1Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA.
Insights
Aldosterone synthase deficiency, a rare genetic disorder, can manifest in adulthood with hyperkalemia. This condition, caused by CYP11B2 gene mutations, is often linked to childhood failure to thrive.
Area of Science:
- Endocrinology
- Genetics
- Molecular Biology
Background:
- Aldosterone synthase deficiency, caused by CYP11B2 gene mutations, typically presents in infancy with electrolyte imbalances and failure to thrive.
- Adults with this condition are generally asymptomatic, making late-onset presentation rare.
Observation:
- A middle-aged patient presented with hyperkalemia, with a history of failure to thrive in infancy.
- Biochemical analysis revealed elevated plasma renin activity (PRA) with low serum and urinary aldosterone and its metabolites, alongside normal or slightly elevated 18-hydroxycorticosterone levels.
Findings:
- The patient was diagnosed with type 1 aldosterone synthase deficiency.
- Genetic analysis identified a homozygous duplication in the CYP11B2 gene, resulting in an inactive aldosterone synthase enzyme.
- Functional studies confirmed the enzyme's complete inactivity due to the identified mutation.
Implications:
- Aldosterone synthase deficiency is an uncommon cause of hyperreninemic hypoaldosteronism presenting in adulthood.
- Suspicion should be raised in adults with hyperreninemic hypoaldosteronism if there is a history of childhood failure to thrive or no other identifiable cause.
- This case highlights the importance of considering genetic disorders in atypical presentations of endocrine conditions.
Abstract:
Aldosterone synthase deficiency due to mutations in the CYP11B2 gene usually presents in infancy with electrolyte abnormalities and failure to thrive, whereas affected adults are usually asymptomatic. We describe a patient who first came to medical attention in middle age when he developed hyperkalemia after preparation for a barium enema. Past medical history was notable for failure to thrive in infancy. He had elevated PRA with low serum and urinary levels of aldosterone and its metabolites and normal or slightly elevated levels of 18-hydroxycorticosterone. These findings suggested a diagnosis of type 1 aldosterone synthase deficiency. The patient had a homozygous duplication of six nucleotides at codon 143 in exon 3 of CYP11B2, leading to the insertion of two amino acid residues (Arg-Leu). When the corresponding mutant complementary DNA was expressed in cultured cells, the resulting enzyme was completely inactive, confirming the diagnosis. We conclude that aldosterone synthase deficiency represents an unusual cause of hyperreninemic hypoaldosteronism presenting in adult life, but it should be suspected if the past medical history is positive for failure to thrive in childhood or if the patient manifests no other recognized causes of hyperreninemic hypoaldosteronism.