A Rare Case of Apparent Mineralocorticoid Excess Presenting as Endocrine Hypertension

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Apparent mineralocorticoid excess (AME) is a rare genetic disorder characterized by hypertension, hypokalemia, and metabolic alkalosis.
• It is caused by mutations in the HSD11B2 gene, which encodes the enzyme 11-beta-hydroxysteroid dehydrogenase type 2.
• This enzyme is responsible for inactivating cortisol in mineralocorticoid target tissues, preventing its binding to the mineralocorticoid receptor.

Observation:

• A 3-year-old boy presented with polyuria, polydipsia, and growth failure, alongside severe underweight and hypertension.
• Clinical evaluation excluded secondary causes of hypertension and significant family history.
• Endocrine workup revealed hyporeninemic hypoaldosteronism, suggesting AME or Liddle syndrome.

Findings:

• Clinical exome sequencing identified a novel homozygous mutation (911A>G; p.His304Arg) in exon 5 of the HSD11B2 gene.
• This missense mutation confirmed the diagnosis of apparent mineralocorticoid excess (AME).

Implications:

• This case highlights the importance of genetic testing in diagnosing rare endocrine disorders like AME.
• The identification of a novel HSD11B2 mutation expands the known spectrum of genetic variations causing AME.
• Early diagnosis and management of AME are crucial for preventing long-term complications such as cardiovascular disease and growth impairment.