A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH
Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by mild elevations in serum calcium and relatively low urinary calcium excretion. It results from an elevated set point in serum calcium arising from variants in the calcium-sensing receptor (CaSR) g...
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| Format: | Article |
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Wiley
2020-01-01
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| Series: | Case Reports in Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2020/8752610 |
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| author | Sachin K. Majumdar Tess Jacob Allen Bale Allison Bailey Jeffrey Kwon Terence Hughes Andrea L. Barbieri William Laskin Paul Cohen Tobias John Eric Carling |
| author_facet | Sachin K. Majumdar Tess Jacob Allen Bale Allison Bailey Jeffrey Kwon Terence Hughes Andrea L. Barbieri William Laskin Paul Cohen Tobias John Eric Carling |
| author_sort | Sachin K. Majumdar |
| collection | DOAJ |
| description | Familial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by mild elevations in serum calcium and relatively low urinary calcium excretion. It results from an elevated set point in serum calcium arising from variants in the calcium-sensing receptor (CaSR) gene but also AP2S1 and GNA11 genes, which encode for adaptor-related protein complex 2 and G11 proteins, respectively. The manifestations of FHH can vary and sometimes overlap with primary hyperparathyroidism making the diagnosis challenging. Case Presentations. We report a mother and daughter with a novel heterozygous variant in the CaSR gene resulting in a serine to leucine substitution at position 147 (S147L) of the CaSR. Both patients had mild hypercalcemia, relatively low urinary calcium excretion, elevated calcitriol, and low-to-normal intact PTH. The proband (daughter) presented with symptoms associated with hypercalcemia and was incidentally found to have a bony lesion suspicious for osteitis fibrosa cystica, and she was also diagnosed with sarcoidosis. Subtotal parathyroidectomy revealed normal-weight parathyroid glands comprised of 50–80% parathyroid epithelial cells, which has been documented as within the spectrum of normal. Her mother had no symptoms, and no intervention was pursued. Conclusion. We report a novel variant in the CaSR associated with FHH in two patients with similar biochemical features yet differing clinical manifestations. While the relationship of the bony findings and parathyroid histology with this variant remains unclear, these cases enrich our knowledge of CaSR physiology and provide further examples of how varied the manifestations of FHH can be. |
| format | Article |
| id | doaj-art-2a84e0cf8f9944d1875aae3830013ced |
| institution | Kabale University |
| issn | 2090-6501 2090-651X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Endocrinology |
| spelling | doaj-art-2a84e0cf8f9944d1875aae3830013ced2025-08-20T03:54:43ZengWileyCase Reports in Endocrinology2090-65012090-651X2020-01-01202010.1155/2020/87526108752610A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTHSachin K. Majumdar0Tess Jacob1Allen Bale2Allison Bailey3Jeffrey Kwon4Terence Hughes5Andrea L. Barbieri6William Laskin7Paul Cohen8Tobias John Eric Carling9Department of Endocrinology, Bridgeport Hospital, Yale New Haven Health System, Bridgeport, CT, USADepartment of Internal Medicine, Bridgeport Hospital, Yale New Haven Health System, Bridgeport, CT, USADepartment of Pathology, Yale University School of Medicine, New Haven, CT, USADepartment of Pathology, Yale University School of Medicine, New Haven, CT, USADepartment of Internal Medicine, Bridgeport Hospital, Yale New Haven Health System, Bridgeport, CT, USADepartment of Radiology, Bridgeport Hospital, Yale New Haven Health System, Bridgeport, CT, USADepartment of Pathology, Yale University School of Medicine, New Haven, CT, USADepartment of Pathology, Yale University School of Medicine, New Haven, CT, USADepartment of Pathology, Yale University School of Medicine, New Haven, CT, USASection of Endocrine Surgery, Department of Surgery, Yale University School of Medicine, New Haven, CT, USAFamilial hypocalciuric hypercalcemia (FHH) is considered a relatively benign condition characterized by mild elevations in serum calcium and relatively low urinary calcium excretion. It results from an elevated set point in serum calcium arising from variants in the calcium-sensing receptor (CaSR) gene but also AP2S1 and GNA11 genes, which encode for adaptor-related protein complex 2 and G11 proteins, respectively. The manifestations of FHH can vary and sometimes overlap with primary hyperparathyroidism making the diagnosis challenging. Case Presentations. We report a mother and daughter with a novel heterozygous variant in the CaSR gene resulting in a serine to leucine substitution at position 147 (S147L) of the CaSR. Both patients had mild hypercalcemia, relatively low urinary calcium excretion, elevated calcitriol, and low-to-normal intact PTH. The proband (daughter) presented with symptoms associated with hypercalcemia and was incidentally found to have a bony lesion suspicious for osteitis fibrosa cystica, and she was also diagnosed with sarcoidosis. Subtotal parathyroidectomy revealed normal-weight parathyroid glands comprised of 50–80% parathyroid epithelial cells, which has been documented as within the spectrum of normal. Her mother had no symptoms, and no intervention was pursued. Conclusion. We report a novel variant in the CaSR associated with FHH in two patients with similar biochemical features yet differing clinical manifestations. While the relationship of the bony findings and parathyroid histology with this variant remains unclear, these cases enrich our knowledge of CaSR physiology and provide further examples of how varied the manifestations of FHH can be.http://dx.doi.org/10.1155/2020/8752610 |
| spellingShingle | Sachin K. Majumdar Tess Jacob Allen Bale Allison Bailey Jeffrey Kwon Terence Hughes Andrea L. Barbieri William Laskin Paul Cohen Tobias John Eric Carling A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH Case Reports in Endocrinology |
| title | A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH |
| title_full | A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH |
| title_fullStr | A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH |
| title_full_unstemmed | A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH |
| title_short | A Novel Variant in the Calcium-Sensing Receptor Associated with Familial Hypocalciuric Hypercalcemia and Low-to-Normal PTH |
| title_sort | novel variant in the calcium sensing receptor associated with familial hypocalciuric hypercalcemia and low to normal pth |
| url | http://dx.doi.org/10.1155/2020/8752610 |
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