apparent mineralocorticoid excess

Apparent mineralocorticoid excess (AME) is an endocrine and renal disorder that causes the body to behave as though it is producing too much of the salt-retaining hormone aldosterone, even though aldosterone levels are actually low. The condition is triggered by changes in the HSD11B2 gene, which normally helps inactivate cortisol before it reaches mineralocorticoid receptors in the kidneys. Without this protective step, cortisol overstimulates these receptors, leading to severe salt retention, potassium loss, and very early-onset high blood pressure. AME can present in infancy or early childhood and affects individuals of all sexes. Fewer than one in a million people are thought to be affected worldwide, making it a very rare condition.

Symptoms usually appear in the first months or years of life. Cardiovascular features dominate early presentation, with severe hypertension that is difficult to control and is accompanied by low plasma renin and aldosterone levels. Renal involvement becomes apparent through excessive urinary sodium loss, hypokalemia, and metabolic alkalosis. Many children drink large amounts of water to compensate for salt-driven thirst and may develop nephrocalcinosis or gradual loss of kidney function if untreated. Growth concerns are common: babies may be small at birth, have trouble gaining weight, and later exhibit short stature or failure to thrive. Over time, long-standing high blood pressure can lead to left ventricular hypertrophy, hypertensive retinopathy, or, in a minority of individuals, stroke. Not all individuals experience all features, and severity varies considerably from mild blood-pressure elevation to life-threatening complications.

AME is caused by pathogenic variants in the HSD11B2 gene. This gene instructs kidney cells to produce the enzyme 11-beta-hydroxysteroid dehydrogenase type 2, which normally converts active cortisol into inactive cortisone. When the enzyme is deficient, cortisol overwhelms mineralocorticoid receptors, resulting in salt retention and potassium loss. The disorder is inherited in an autosomal recessive pattern, meaning a child must receive one altered copy of HSD11B2 from each parent to be affected. Parents who carry a single altered copy are typically healthy but have a 25 percent chance with each pregnancy of having a child with AME. The condition is more common when parents share a common ancestor because relatives are more likely to carry the same rare variant. Carrier testing and genetic counseling can help families understand their individual risks and options for future pregnancies.

Currently, management focuses on supportive care and symptom control. The main goal is to lower blood pressure, correct low potassium levels, and protect kidney and cardiovascular health. Treatment plans often include medications that counteract mineralocorticoid effects, dietary salt restriction, and careful potassium supplementation, all tailored to the individual’s needs. Because AME can affect several organ systems, long-term care is best provided by a multidisciplinary team that may include pediatric nephrology, cardiology, endocrinology, and nutrition specialists. Regular surveillance of blood pressure, serum electrolytes, and kidney function is essential to detect complications early and adjust therapy over time. Genetic counseling is recommended for affected individuals and their relatives to discuss inheritance, carrier testing, and reproductive options. Patients should work closely with their healthcare team to determine the most appropriate treatment strategy for their circumstances.

With prompt diagnosis and effective blood-pressure control, many individuals with AME can lead active lives and avoid the most serious complications. Nevertheless, long-standing hypertension can cause kidney damage, heart enlargement, or stroke if management is delayed or suboptimal. Outcomes depend on how early treatment is started, how well blood pressure and potassium levels are maintained, and access to specialized care. Severity and symptoms vary widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with AME and with genetic counselors who can provide ongoing guidance and support.

Clinical trials are underway exploring new treatment approaches for AME and related forms of childhood hypertension. Individuals interested in participating can search ClinicalTrials.gov or discuss eligibility with their healthcare team.