ESPE Abstracts

Background: Isolated hyperreninemic hypoaldosteronism due to aldosterone synthase deficiency is a rare autosomal recessive disorder linked to aldosterone biosynthesis defect (involving CYP11B2 gene). Its clinical presentation varies with age: during the first weeks of life it usually presents with salt-wasting syndrome (with severe hyponatremia, hyperkalemia, metabolic acidosis, vomiting, signs of dehydration) while in children it is usually characterized by failure to thrive, anorexia, mild dehydration and electrolyte abnormalities. Growth retardation may persist throughout childhood without appropriate therapy.

Objective and hypotheses: We describe the clinical onset and course and the genetic evaluation of five patients with primary hyperreninemic hypoaldosteronism in Tuscany.

Method: Five patients (two males, three females) came to our attention for electrolytes disorder (hyponatriemia and hyperkaliemia, increased plasmatic renin activity, low or normal aldosteron level) with normal cortisol and sex hormones values. Two of them presented with neonatal salt-wasting syndrome. They all have been suspected for primary hyperreninemic hypoaldosteronism on the basis of clinical and laboratory features. Appropriate therapy with fludrocortisone was started in four of them with general improvement. All of the patients underwent genetic analysis: amplification by PCR and Sanger sequencing of nine exons of CYP11B2.

Results: Three patients showed mutations in homozygous state: c.1231G>C (p.Gly411Arg) in exon 8, c.554C>T (p.Thr185Ile in exon 3, c.780G>A (p.Trp260*) in exon 4. One patient showed two mutations in heterozygous state: c.554C>T (p.Thr185Ile) in exon 3 and c.763G>T (p.Glu255*) in exon 4. They all supported the diagnosis of hypoaldosteronism. One patient present not detectable gene mutations.

Conclusion: Clinical and laboratoristic suspect of hyperreninemic hypoaldosteronism should be supported by genetic confirmation. Therapy with fludrocortisone should be life-long administered in these patients in order to ensure a good quality of life and reduce long-term damage.