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A Case of a Heterozygous Inactivating CASR Variant with Adult-Onset Symptomatic Hypercalcemia Requiring Extensive Surgery

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Abstract

We describe the case of an adult female patient with symptomatic familial hypocalciuric hypercalcemia requiring a step-wise therapeutic approach and the eventual need for a total parathyroidectomy and thyroidectomy to cure symptoms. Genetic analysis demonstrated a heterozygous R227L inactivating CASR gene variant, previously only described in neonatal severe hyperparathyroidism. Post-operative histology showed diffuse hyperplasia of all four parathyroid glands along with the presence of intrathyroidal parathyroid tissue. With regard to clinical management this case suggests that familial hypocalciuric hypercalcemia should be classified as an atypical form of primary hyperparathyroidism rather than a distinct entity.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium

    Laurens Veldeman

  2. Department of Endocrinology, AZ St.-Blasius Dendermonde, Dendermonde, Belgium

    Laurens Veldeman & Saskia Robbrecht

  3. Center for Human Genetics, University Hospitals Leuven, Leuven, Belgium

    Jeroen Breckpot

  4. Department of Pathology, University Hospitals Leuven, Leuven, Belgium

    Birgit Weynand

  5. Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium

    Brigitte Decallonne

Authors
  1. Laurens Veldeman
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  2. Saskia Robbrecht
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  3. Jeroen Breckpot
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  4. Birgit Weynand
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  5. Brigitte Decallonne
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Contributions

LV conducted patient data collection and wrote the first draft. SR coordinated the diagnostic assessment, treatment and follow-up of the patient. SR, JB and BD helped writing the draft and critically reviewed it. JB reviewed the genetic analysis. BW reviewed the histopathology.

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Correspondence to Laurens Veldeman.

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Laurens Veldeman, Saskia Robbrecht, Jeroen Breckpot, Birgit Weynand and Brigitte Decallonne declare that they have no conflicts of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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223_2020_693_MOESM1_ESM.pdf

Supplementary file1 (PDF 117 kb) Supplemental Figure 1. Electropherogram of CaSR exon 4 fragment, wild type (WT) and proband (P), black box shows nucleotide change point mutation G→T substitution in codon 680 in heterozygous state, leading to amino acid change position 227 Arginine (R) to Leucine (L).

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Veldeman, L., Robbrecht, S., Breckpot, J. et al. A Case of a Heterozygous Inactivating CASR Variant with Adult-Onset Symptomatic Hypercalcemia Requiring Extensive Surgery. Calcif Tissue Int 107, 104–108 (2020). https://doi.org/10.1007/s00223-020-00693-4

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  • DOI: https://doi.org/10.1007/s00223-020-00693-4

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