Type 1 Aldosterone Synthase Deficiency Presenting in a Middle-Aged Man¹

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.

Aldosterone signaling defect in young infants: single-center report and review

“…The termination of mineralocorticoid therapy in ASD patients may lead to postural hypotension and hyperkalemia when triggered by stress due to dehydration or salt intake reduction [20]. Generalized weakness has also been reported in a middle aged man with ASD [21] which was also present in P3's mother in our study.…”

Mineralocorticoids and Cardiac Fibrosis: The Decade in Review

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“…First, the two Japanese papers appear diametrically opposed and are not easy to reconcile. Second, on semiquantitative PCR for the biosynthetic enzymes required for aldosterone biosynthesis, levels in heart tissue appear three to four orders of magnitude lower than in adrenal 21 . Given that under such conditions each step becomes rate limiting, it is difficult to see how the relatively substantial steroidogenesis implied by a 30% transcardiac increase in systolic failure can reflect steroidogenesis by the myocardium holus‐bolus; it is altogether more probable that it reflects coordinate expression of relatively higher levels of enzymes in a restricted cell population, for example within the coronary vasculature.…”

Surgery for thyroid cancer invading into the tracheal wall

“…на) [3]. В эксперименте in vitro данная мутация проявлялась полной потерей ферментативной ак тивности.…”

“…При отсутствии висцеральных проявлений и тяжелого остеопороза эти случаи не требуют оперативного вмешательства и могут вестись консервативно. Опубликованы работы по предотвращению кост ных потерь и переломов при мягких формах ПГПТ с помощью бисфосфонатов, а также показана их эффективность для борьбы с гиперкальциемическим кризом при тяжелом течении заболевания [3,4,7,9]. В настоящее время появились единичные сообщения о возможности снижении уровня каль ция и ПТГ кальцимиметиками при неоперабель ных формах риска ОЩЖ и рецидивирующем ПГПТ [3,5,8,10].…”