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Unusual presentation of more common disease/injury
CASE REPORT
Primary aldosteronism associated with a germline variant in CACNA1H
  1. Kendra Wulczyn1,
  2. Edward Perez-Reyes2,
  3. Robert L Nussbaum3 and
  4. Meyeon Park1
  1. 1Department of Medicine, UCSF, San Francisco, California, USA
  2. 2Department of Pharmacology, University of Virginia, Charlottesville, Virginia, USA
  3. 3Invitae Corporation, San Francisco, California, USA
  1. Correspondence to Dr Meyeon Park, meyeon.park{at}ucsf.edu

Abstract

The CACNA1H gene encodes the pore-forming α1 subunit of the T-type voltage-dependent calcium channel CaV3.2, expressed abundantly in the adrenal cortex. Mutations in CACNA1H are associated with various forms of primary aldosteronism (PA), including familial hyperaldosteronism type 4 (FH4). We describe a patient with refractory hypokalaemia and elevated aldosterone secretion independent of renin activity. Despite the absence of overt hypertension in this patient, the laboratory evaluation was consistent with a diagnosis of PA. Whole-exome sequencing revealed a de novo missense variant, R890H, in the voltage sensing domain of CACNA1H. Expression of the variant channel in cells resulted in decreased whole-cell current, consistent with a loss-of-function. We hypothesise this variant is the genetic cause of pathological aldosterone secretion in this patient, and thereby expand the current understanding of the genetic basis of FH4.

  • fluid electrolyte and acid–base disturbances
  • genetics
  • adrenal disorders

https://doi.org/10.1136/bcr-2018-229031

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    Footnotes

    • Contributors MP and RLN initiated this project and were involved in the clinical management. MP is the guarantor. RLN and EP-R were responsible for the genetic testing, including laboratory testing of the mutated calcium channel. KW wrote the majority of the case report, with all authors contributing to the revision process.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Correction notice This article has been corrected since it was published Online First, patient’s perspective has been added to this article.

    • Patient consent for publication Obtained.