Advances in Diabetes & Endocrinology
Case Report
A Case Report of Calcium- Sensing Receptor Gene Variant CASR (c.659G>A; p.R220Q) and Primary Hyperparathyroidism
Fang ME1*, Joad SS2, Posey JE1 and Gaba R2
1Department of Molecular and Human Genetics, Baylor College of
Medicine, Houston, TX 77030, USA
2Department of Medicine, Section of Endocrinology, Diabetes and
Metabolism, Baylor College of Medicine, Houston TX 77030, USA
*Address for Correspondence:
Fang ME, Department of Molecular and Human Genetics, Baylor College of
Medicine, Houston, TX 77030, USA; E-mail: mary.fang@bcm.edu; Phone:
214-726-2257
Submission: 10 October, 2022
Accepted: 07 November, 2022
Published: 11 November, 2022
Copyright: © 2022 Fang ME, et al. This is an open access article
distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly cited.
Abstract
Background: Primary hyperparathyroidism (PHPT) results from
excessive parathyroid hormone from one or more overactive
parathyroid gland(s). An estimated 90% of PHPT cases are sporadic,
and up to 10% are inherited, comprising hereditary hyperparathyroidism
(HHPT). Genetic testing can aid in diagnosis and management and
influence testing of other family members.
Case Report: A 42-year-old female with hypercalcemia
(diagnosed at 23 years) and nephrolithiasis due to PHPT was referred
to endocrinology for further management and evaluation following
3-gland parathyroidectomy. Pre-operative workup showed calcium of
11.1mg/dL and PTH of 177pg/mL. Sestamibi showed persistent activity
in the mid-to-inferior aspect of right thyroid lobe. Post-operative
pathology showed mildly hypercellular parathyroid in left superior
and right superior gland, normocellular left inferior gland. iPTH levels
normalized post-surgery. Genetic evaluation was performed, given
her early-onset hypercalcemia, multi-gland involvement, and notable
family history (mother and daughter with primary hyperparathyroidism,
maternal grandfather with parathyroidectomy, and maternal aunt
with multiple bone fractures). Invitae hyperparathyroidism panel
revealed a likely pathogenic variant in CASR (c.659G>A; p.R220Q).
Discussion: Our case is the second report of this likely pathogenic
variant, previously reported in a 29-year-old proband diagnosed
with familial hypocalciuric hypercalcemia (FHH) after remaining
hypercalcemic following subtotal thyroidectomy. Despite the marked
phenotypic heterogeneity (clinical presentation and response to
surgery), both our case and this previous patient shared a personal
history and family history of hypercalcemia, suggesting contributions to
both causes of hypercalcemia from the same variant.
Conclusion: We interpret the structural and functional change to
the CaSR to be a predisposition for both FHH and PHPT. Our case adds
to the limited existing data about the variable expressivity of genes
implicated in the pathogenesis of both FHH and HHPT.