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

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.

Mechanisms of Renal Control of Potassium Homeostasis in Complete Aldosterone Deficiency

“…Our data are in line with observations in humans with type 1 aldosterone deficiency, who are usually still able to adapt renal K + excretion and to stay more or less in K + balance. 38 Likewise, adrenalectomized animals 23,24,39 were shown to augment renal K + excretion in response to an increased dietary K + intake, although usually at the expense of more or less elevated plasma K + levels. Previous studies on adrenalectomized rats and rabbits indicated that a high-K + diet increases renal Na + and K + channel activities independent from aldosterone.…”

Two novel mutations of the CYP11B2 gene in a Japanese patient with aldosterone deficiency type 1

“…2A). Sequencing of CYP11B2 in the patient also identified a heterozygous C to A change at codon thase deficiency type 1 [2,[3][4][5][6]12]. Furthermore, several missense mutations (S315R, L324Q, R374W, R384P, L451F, and L461P) have been identified in type 1 patients.…”

“…Aldosterone synthase deficiency type 1 is caused by mutations in CYP11B2 that completely abolish enzymatic activity [3][4][5][6]. In contrast, aldosterone synthase deficiency type 2 is characterized by low aldosterone levels, increased 18OHB and 18OHDOC levels, and an increased 18OHB/aldosterone ratio.…”

Hypotensions d’origine endocrinienne

“…Elles se traduisent cliniquement par des épisodes de déshydratation extracellulaire avec retard staturo-pondéral, s'améliorant un peu avec l'âge. Un cas a pu être rapporté chez l'adulte [37]. Les activités enzymatiques 18 hydroxylase et 18 oxydase sont portées par un complexe possédant également une faible activité 11 hydroxylase codée par le gène CYP11B2.…”