Congenital hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency type I in a Portuguese patient - Case report and review of literature.

Beatriz Vale,Francisco Carrilho,Adriana de Sousa Lages,Patrícia Oliveira,Isabel Dinis,Rita Cardoso,Alice Mirante

doi:10.20945/2359-3997000000107

Abstract

Hyperreninemic hypoaldosteronism due to aldosterone synthase (AS) deficiency is a rare condition typically presenting as salt-wasting syndrome in the neonatal period. A one-month-old Portuguese boy born to non-consanguineous parents was examined for feeding difficulties and poor weight gain. A laboratory workup revealed severe hyponatremia, hyperkaliaemia and high plasma renin with unappropriated normal plasma aldosterone levels, raising the suspicion of AS deficiency. Genetic analysis showed double homozygous of two different mutations in the CYP11B2 gene: p.Glu198Asp in exon 3 and p.Val386Ala in exon 7. The patient maintains regular follow-up visits in endocrinology clinics and has demonstrated a favourable clinical and laboratory response to mineralocorticoid therapy. To our knowledge, this is the first Portuguese case of AS deficiency reported with confirmed genetic analysis.

Highlights

Aldosterone is a mineralocorticoid hormone secreted exclusively in the zona glomerulosa (ZG) of the adrenal cortex and acts in distal renal tubules by increasing sodium reabsorption and promoting urinary potassium excretion
The aldosterone synthesis is dependent on aldosterone synthase (AS), an enzyme encoded by the CYP enzyme 11B2 (CYP11B2) gene, one of the cytochrome P450 enzymes (P450c11Aldo)
Besides the clinical similarity at presentation, patients frequently have genital abnormalities and a hormonal profile that is clearly distinct – instead of an isolated aldosterone deficiency with exclusively mineralocorticoid deficiency, on most patients (> 95%) with congenital adrenal hyperplasia (CAD) due to 21-hydroxylase deficiency (CYP21A2), we found a combined aldosterone and cortisol synthesis deficiency associated with raised 17OHP, with elevated adrenal androgens as a hallmark of the diagnosis [24]

Summary

SUMMARY

Hyperreninemic hypoaldosteronism due to aldosterone synthase (AS) deficiency is a rare condition typically presenting as salt-wasting syndrome in the neonatal period. A one-month-old Portuguese boy born to non-consanguineous parents was examined for feeding difficulties and poor weight gain. A laboratory workup revealed severe hyponatremia, hyperkaliaemia and high plasma renin with unappropriated normal plasma aldosterone levels, raising the suspicion of AS deficiency. Genetic analysis showed double homozygous of two different mutations in the CYP11B2 gene: p.Glu198Asp in exon 3 and p.Val386Ala in exon 7. The patient maintains regular follow-up visits in endocrinology clinics and has demonstrated a favourable clinical and laboratory response to mineralocorticoid therapy.To our knowledge, this is the first Portuguese case of AS deficiency reported with confirmed genetic analysis.

INTRODUCTION

DISCUSSION

CONCLUSIONS