| Core fact | Summary | Key details / ontology suggestions | Evidence |
|---|---|---|---|
| Identifiers | Apparent mineralocorticoid excess (AME) is a rare monogenic mineralocorticoid-hypertension disorder caused by impaired cortisol inactivation. | MONDO:0009025; OMIM: 218030; MeSH: D043204 (“Mineralocorticoid Excess Syndrome, Apparent”); category: Mendelian / autosomal recessive low-renin hypertension. Synonyms: AME, apparent mineralocorticoid excess syndrome, mineralocorticoid excess syndrome apparent. | (pqac-00000000, pqac-00000009, pqac-00000007) |
| Cause / inheritance | Classic AME is caused by biallelic germline pathogenic variants in **HSD11B2**, encoding 11β-HSD2; inheritance is autosomal recessive. | Causal gene: **HSD11B2**; protein: hydroxysteroid 11-beta dehydrogenase 2; mechanism is usually loss of function. Founder effects and consanguinity are recurrent in reported families. Nonclassic AME reflects partial deficiency with genetic/epigenetic contribution. | (pqac-00000001, pqac-00000015, pqac-00000017, pqac-00000018) |
| Hallmark phenotype | Core phenotype is childhood-onset low-renin, low-aldosterone hypertension with hypokalemic metabolic alkalosis due to cortisol-mediated mineralocorticoid receptor activation. | Suggested HPO: Hypertension, Hypokalemia, Metabolic alkalosis, Low renin hypertension, Failure to thrive, Polyuria, Polydipsia, Nephrocalcinosis, Left ventricular hypertrophy, Low birth weight. Classic AME usually presents from infancy/childhood; nonclassic AME often in adolescents/adults and may be normotensive or mildly hypertensive. | (pqac-00000001, pqac-00000004, pqac-00000006, pqac-00000010) |
| Diagnostic signature | Biochemical hallmark is impaired cortisol-to-cortisone conversion with suppressed renin and aldosterone plus elevated cortisol/cortisone metabolite ratios; confirmation is by genetic testing. | Typical tests: plasma renin activity or concentration low/suppressed; aldosterone low; urinary steroid profile with elevated (THF + 5αTHF)/THE and/or serum/urine cortisol:cortisone ratio; classic AME often has 11βHSD2 activity ~1–6%, nonclassic ~40–60%. ClinicalTrials.gov eligibility required low renin, low aldosterone, elevated urinary cortisol/cortisone metabolite ratio, and two HSD11B2 mutations. | (pqac-00000021, pqac-00000009, pqac-00000007) |
| Mechanism / pathophysiology | Loss of renal 11β-HSD2 prevents conversion of cortisol to cortisone, allowing cortisol to activate mineralocorticoid receptor despite low aldosterone, driving sodium retention and potassium wasting. | Upstream defect: HSD11B2 loss/partial loss. Downstream pathway: MR activation → ENaC and Na+/K+-ATPase upregulation → sodium and water retention, hypokalemia, low renin, hypertension. Primary anatomy: kidney distal nephron/collecting duct; additional expression in placenta, colon, brain. Suggested GO/UBERON/CL concepts: cortisol catabolic process, mineralocorticoid receptor signaling pathway, kidney, placenta, colon, renal tubular epithelial cell. | (pqac-00000009, pqac-00000012, pqac-00000015) |
| Treatment / real-world management | Mainstays are salt restriction, mineralocorticoid receptor blockade, potassium-sparing approaches, potassium replacement, and selected glucocorticoid suppression therapy; renal transplant can cure the endocrine-renal defect in advanced kidney failure. | Reported regimens: spironolactone or eplerenone for classic and nonclassic AME; low-dose nonclassic examples include spironolactone 12.5–25 mg/day or eplerenone 25–50 mg/day; classic AME may need higher weight-based MR antagonist dosing plus potassium; amiloride blocks ENaC mechanistically; glucocorticoids may suppress ACTH-driven cortisol production in selected classic cases; kidney transplantation reported as curative. Suggested MAXO: low sodium diet, mineralocorticoid receptor antagonist therapy, potassium supplementation, renal transplantation. | (pqac-00000023, pqac-00000010, pqac-00000022) |
| Prognosis / statistics | Prognosis depends strongly on early diagnosis and treatment; untreated disease can cause severe target-organ injury. | Long-term data cited in review: cardiovascular mortality 19%, persistent nephrocalcinosis 89%, kidney failure 15% in a 36-patient classic AME series; one long-term family follow-up found worst outcomes in the sibling with longest diagnostic delay. Natural-history study NCT00474942 enrolled 130 participants and notes some patients progress despite spironolactone. | (pqac-00000010, pqac-00000007) |
| Evidence limitations | Evidence base is dominated by case reports, small family series, reviews, and observational natural-history data; randomized trials and population prevalence estimates for classic AME are lacking. | Classic AME prevalence remains unclear; nonclassic AME estimate of 7.1% comes from one Chilean primary-care cohort and should not be generalized. Recent 2023–2024 literature mainly provides reviews, low-renin hypertension synthesis, epigenetic discussion, and case-series updates rather than interventional trials or gene therapy. | (pqac-00000003, pqac-00000005, pqac-00000007, pqac-00000015) |


*Table: This table summarizes the most important knowledge-base facts for apparent mineralocorticoid excess, including identifiers, etiology, phenotype, diagnosis, mechanism, treatment, prognosis, and major evidence gaps. It is designed as a compact reference for disease curation and clinical interpretation.*