Primary aldosteronism with intellectual disability associated with CACNA1H and PPP2R5D mutations: a case report with review of literature
Abstract
Mutations in the CACNA1H and PPP2R5D genes have been associated with functional abnormalities affecting both the endocrine and nervous systems. The CACNA1H gene encodes the T-type calcium channel CaV3.2, and pathogenic variants may alter channel activation and inactivation, resulting in increased intracellular calcium influx. Elevated intracellular calcium in adrenal zona glomerulosa cells acts as a key signal for aldosterone biosynthesis, thereby promoting excessive aldosterone secretion and contributing to the development of hypertension. The PPP2R5D gene encodes a regulatory subunit of protein phosphatase 2A (PP2A). Mutations in this gene may disrupt the regulatory function of PP2A, impairing the dephosphorylation of key neuroproteins and consequently affecting neural signal transduction and brain function. Cases of early-onset hypertension accompanied by intellectual disability associated with concurrent CACNA1H and PPP2R5D mutations remain rare. We report the case of an 18-year-old female presenting with early-onset hypertension and intellectual disability. Hypertension was first diagnosed at the age of 10 years and was accompanied by recurrent dizziness and headache. Physical examination revealed central obesity and signs of hyperandrogenism. Laboratory evaluation demonstrated elevated aldosterone levels with suppressed plasma renin activity, suggesting primary aldosteronism. Genetic analysis identified heterozygous variants in CACNA1H (c.6866C>T) and PPP2R5D (c.985A>G). Based on the clinical features and genetic findings, the patient was diagnosed with familial hyperaldosteronism type IV complicated by intellectual disability. This case highlights the importance of considering genetic forms of primary aldosteronism in young patients with early-onset hypertension and atypical clinical manifestations. Genetic testing may facilitate accurate diagnosis and guide individualized management.
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BibTeX
@article{zhang2026primary,
title = {{Primary aldosteronism with intellectual disability associated with CACNA1H and PPP2R5D mutations: a case report with review of literature}},
author = {Wennan Zhang and Yiwen Zhang and Yangyang Wang and Yu Xue and Lili Xu and Hui Yan},
journal = {Endocrine Journal},
year = {2026},
month = aug,
doi = {10.1507/endocrj.ej26-0175},
url = {https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0175/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Primary aldosteronism with intellectual disability associated with CACNA1H and PPP2R5D mutations: a case report with review of literature
AU - Wennan Zhang
AU - Yiwen Zhang
AU - Yangyang Wang
AU - Yu Xue
AU - Lili Xu
AU - Hui Yan
PY - 2026
DA - 2026/08/26
JO - Endocrine Journal
DO - 10.1507/endocrj.ej26-0175
UR - https://www.jstage.jst.go.jp/article/endocrj/advpub/0/advpub_EJ26-0175/_article
AB - Mutations in the CACNA1H and PPP2R5D genes have been associated with functional abnormalities affecting both the endocrine and nervous systems. The CACNA1H gene encodes the T-type calcium channel CaV3.2, and pathogenic variants may alter channel activation and inactivation, resulting in increased intracellular calcium influx. Elevated intracellular calcium in adrenal zona glomerulosa cells acts as a key signal for aldosterone biosynthesis, thereby promoting excessive aldosterone secretion and contributing to the development of hypertension. The PPP2R5D gene encodes a regulatory subunit of protein phosphatase 2A (PP2A). Mutations in this gene may disrupt the regulatory function of PP2A, impairing the dephosphorylation of key neuroproteins and consequently affecting neural signal transduction and brain function. Cases of early-onset hypertension accompanied by intellectual disability associated with concurrent CACNA1H and PPP2R5D mutations remain rare. We report the case of an 18-year-old female presenting with early-onset hypertension and intellectual disability. Hypertension was first diagnosed at the age of 10 years and was accompanied by recurrent dizziness and headache. Physical examination revealed central obesity and signs of hyperandrogenism. Laboratory evaluation demonstrated elevated aldosterone levels with suppressed plasma renin activity, suggesting primary aldosteronism. Genetic analysis identified heterozygous variants in CACNA1H (c.6866C>T) and PPP2R5D (c.985A>G). Based on the clinical features and genetic findings, the patient was diagnosed with familial hyperaldosteronism type IV complicated by intellectual disability. This case highlights the importance of considering genetic forms of primary aldosteronism in young patients with early-onset hypertension and atypical clinical manifestations. Genetic testing may facilitate accurate diagnosis and guide individualized management.
SN - 1348-4540
SN - 0918-8959
ER -