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Familial hyperaldosteronism type I

Familial Hyperaldosteronism Type I Research Fallback

⚠️ Fallback MONDO:0007080

Familial Hyperaldosteronism Type I Research Fallback

Deep-research provider attempts were made after the ORPHA:403 leaf disorder was selected:

  • timeout 240 just research-disorder falcon Familial_Hyperaldosteronism_Type_I
  • timeout 180 just research-disorder openai Familial_Hyperaldosteronism_Type_I

Both commands stalled without producing a research output file and were terminated. The curation therefore used the structured Orphanet cache plus fetched PubMed abstracts as the auditable evidence base.

Literature Scope Checked

  • references_cache/ORPHA_403.md: direct Orphanet leaf record for familial hyperaldosteronism type I, including definition, autosomal dominant inheritance, exact MONDO and OMIM mappings, CYP11B1/CYP11B2 fusion-gene assertions, and HPO phenotype rows.
  • references_cache/PMID_1731223.md: seminal human study identifying unequal crossover producing a chimeric CYP11B1/CYP11B2 gene under ACTH control.
  • references_cache/PMID_35778363.md: clinical review summarizing familial primary hyperaldosteronism forms and confirming that type I results from CYP11B2/CYP11B1 fusion with ACTH-regulated aldosterone synthesis.
  • references_cache/PMID_35012455.md: human diagnostic sequencing paper supporting molecular testing for the CYP11B1/CYP11B2 chimeric form.
  • references_cache/PMID_10618671.md: genetically proven GRA case in which spironolactone replaced dexamethasone after corticosteroid side effects and controlled blood pressure.
  • references_cache/PMID_21451421.md: randomized primary-aldosteronism trial comparing spironolactone and eplerenone, supporting the mineralocorticoid receptor antagonist treatment class.

Curation Conclusions

  • Disease identity is the leaf disorder ORPHA:403, exact to MONDO:0007080 and OMIM:103900. The broader familial hyperaldosteronism group ORPHA:235936 was checked but is not emitted by the repository's structured Orphanet source.
  • The primary mechanism is a CYP11B1/CYP11B2 chimeric gene from unequal crossover, causing ACTH-regulated aldosterone synthase expression, aldosterone and hybrid steroid excess, suppressed renin, variable hypokalemia, and hypertension.
  • Orphanet directly supports the added phenotype profile, including hypertension, dexamethasone-suppressible primary hyperaldosteronism, low renin, hypokalemia, adrenal hyperplasia, secretory adrenocortical adenoma, preeclampsia, epistaxis, caesarean section, intracranial hemorrhage, headache, muscle weakness, and polydipsia.
  • Mechanism-directed treatment includes low-dose glucocorticoid suppression and mineralocorticoid receptor antagonist therapy when corticosteroid side effects or additional blood pressure control make receptor blockade clinically relevant.