A Chinese pedigree with glucocorticoid remediable aldosteronism

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inherited aldosteronism that is often accompanied by early-onset hypertension. GRA is caused by the unequal crossover of the 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropic hormone (ACTH). Here, we describe a Chinese pedigree with three affected subjects. Both the uncle and nephew were hospitalized in our hospital due to early-onset hypertension (onset <20 years old) and were diagnosed with primary aldosteronism (PA). Their laboratory test results revealed hyperaldosteronism, hyporeninemia, a high plasma aldosterone to renin (ARR) ratio, and normal serum potassium (K⁺). Captopril failed to suppress aldosterone secretion. This family had a strong paternal history of hypertension. Thirteen members underwent gene testing, and three of them were found to be GRA positive. Through long-extension PCR (XL-PCR) and direct sequencing, we identified the CYP11B1/CYP11B2 chimeric gene, and with unequal crossover breakpoints located between intron 2 of CYP11B1 and exon 3 of CYP11B2 in the three patients. Low-dose dexamethasone was effective. This is the first family report of GRA in northern China. Moreover, a case of GRA combined with a CACNA1H gene mutation is reported for the first time. We found that dihydropyridine calcium channel blockers (CCBs) combined with aldosterone receptor antagonists exerted good therapeutic effects in controlling blood pressure in GRA patients for whom glucocorticoid therapy was not an option.