An Overview of Familial Hypocalciuric Hypercalcemia
Article Sidebar
Main Article Content
Abstract
Familial hypocalciuric hypercalcemia (FHH) is one of the rare reasons for hypercalcemia. FHH is an autosomal dominant disease that is inheritable. The most common calcium sensitive receptors (CaSR) develop because of the inactivation of. In addition, they also develop due to the function loss of AP2S1 and GNA11. The FHH sickness is characterized by hypercalcemia, hypocalciuria, the regular or increased level of the parathyroid hormone, and normal renal function. The symptoms of hypercalcemia are usually not observed. It is often diagnosed by calculating the calcium/creatine clearance ratio of a 24-hour urine sample, and then genetically looking at it. FHH is usually a benign disorder, and when symptomatic and rarely complications develop, calcimimetics are used or parathyroidectomy can be performed. In conclusion, FHH is a benign and genetically transmitted, moderate cause of hypercalcemia. It is rare and usually asymptomatic.
Article Details
Copyright (c) 2024 Huzmeli C.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The Journal of Clinical Nephrology is committed in making it easier for people to share and build upon the work of others while maintaining consistency with the rules of copyright. In order to use the Open Access paradigm to the maximum extent in true terms as free of charge online access along with usage right, we grant usage rights through the use of specific Creative Commons license.
License: Copyright © 2017 - 2025 | 
Open Access by Journal of Clinical Nephrology is licensed under a Creative Commons Attribution 4.0 International License. Based on a work at Heighten Science Publications Inc.
With this license, the authors are allowed that after publishing with the journal, they can share their research by posting a free draft copy of their article to any repository or website.
Compliance 'CC BY' license helps in:
| Permission to read and download | ✓ |
| Permission to display in a repository | ✓ |
| Permission to translate | ✓ |
| Commercial uses of manuscript | ✓ |
'CC' stands for Creative Commons license. 'BY' symbolizes that users have provided attribution to the creator that the published manuscripts can be used or shared. This license allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author.
Please take in notification that Creative Commons user licenses are non-revocable. We recommend authors to check if their funding body requires a specific license.
Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol 2010;5 Suppl 1:S23-S30. Available from: https://doi.org/10.2215/cjn.05910809
Hoenderop JGJ, Bindels RJM. Epithelial Ca2+ and Mg2+ channels in health and disease. J Am Soc Nephrol 2005;16:15-26. Available from: https://doi.org/10.1681/asn.2004070523
Çolak N. Kalsiyum ve fosfor metabolizması ile ilgili acil durumlar. Dokuzuncu Ulusal İç Hastalıkları Kongresi. 2007;33-5.
Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. 2003;67(9):1959-66. PMID: 12751658. Available from: https://pubmed.ncbi.nlm.nih.gov/12751658/
Frikha F, Snoussi M, Loukil H, Bahloul Z. Chondrocalcinosis revealing familial hypocalciuric hypercalcemia: about one observation. Pan Afr Med J. 2015;20:58. Available from: https://doi.org/10.11604/pamj.2015.20.58.5828
Vargas-Poussou R, Mansour-Hendili L, Baron S, Bertocchio JP, Travers C, Simian C, Houillier P. "Familial hypocalciuric hypercalcemia types 1 and 3 and primary hyperparathyroidism: similarities and differences." The Journal of Clinical Endocrinology & Metabolism 101.5. 2016: 2185-2195. Available from: https://doi.org/10.1210/jc.2015-3442
Hendy Geoffrey N, and David EC Cole. "Ruling in a suspect: the role of AP2S1 mutations in familial hypocalciuric hypercalcemia type 3." The Journal of Clinical Endocrinology & Metabolism 98.12. 2013:4666-4669. Available from: https://doi.org/10.1210/jc.2013-3616
Jones AR, Hare MJ, Brown J, Yang J, Meyer C, Milat F, Allan CA. "Familial hypocalciuric hypercalcemia in pregnancy: diagnostic pitfalls." Journal of Bone and Mineral Research Plus 4.6. 2020: e10362. Available from: https://doi.org/10.1002/jbm4.10362
Lee Janet Y, and Dolores M. Shoback. "Familial hypocalciuric hypercalcemia and related disorders." Best practice & research Clinical endocrinology & metabolism 32.5. 2018: 609-619. Available from: https://doi.org/10.1016/j.beem.2018.05.004
Taïeb D, Lasbleiz A, Paladino NC, Romanet P, Castinetti F, Cuny T, Sebag F. "Familial Hypocalciuric Hypercalcemia: The Challenge of Diagnosis." 2021. Available from: https://doi.org/10.21203/rs.3.rs-773127/v1
Asla Q, Sardà H, Seguí N, Martínez de Pinillos G, Mazarico-Altisent I, Capel I, Aulinas A. "Clinical and outcome comparison of genetically positive vs. negative patients in a large cohort of suspected familial hypocalciuric hypercalcemia." Endocrine 83.3. 2024: 747-756. Available from: https://doi.org/10.1007/s12020-023-03560-y
Hinnie J, Bell E, McKillop E, Gallacher S. "The prevalence of familial hypocalciuric hypercalcemia." Calcified tissue international 68.4. 2001. Available from: https://doi.org/10.1007/s002230001201
Besiroglu H, Sahin S, Otunctemur A, Ozbek E. "Calcium-sensing receptor gene polymorphisms in patients with calcium urolithiasis: a systematic review." Renal Failure 36.8. 2014: 1187-1192. Available from: https://doi.org/10.3109/0886022X.2014.937673
Afzal Muhammad and Pranay Kathuria. "Familial hypocalciuric hypercalcemia." StatPearls [Internet]. StatPearls Publishing, 2023.
Sethi BK, Nagesh VS, Kelwade J, Parekh H, Dukle V. "Utility of cinacalcet in familial hypocalciuric hypercalcemia." Indian Journal of Endocrinology and Metabolism 21.2. 2017: 362-363.Available from: https://doi.org/10.4103/2230-8210.202034
Christensen SE, Nissen PH, Vestergaard P, Heickendorff L, Rejnmark L, Brixen K, Mosekilde L. "Plasma 25-hydroxyvitamin D, 1, 25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism." European journal of endocrinology 159.6. 2008: 719-727. Available from: https://doi.org/10.1530/EJE-08-0440
Riccardi Daniela and Edward M. Brown. "Physiology and pathophysiology of the calcium-sensing receptor in the kidney." American Journal of Physiology-Renal Physiology 298.3. 2010: F485-F499. Available from: https://doi.org/10.1152/ajprenal.00608.2009
Vahe C, Benomar K, Espiard S, Coppin L, Jannin A, Odou MF, Vantyghem MC. "Diseases associated with calcium-sensing receptor." Orphanet journal of rare diseases 12. 2017:1-9. Available from: https://doi.org/10.1186/s13023-017-0570-z
Mrgan M, Nielsen S, Brixen K. Familial hypocalciuric hypercalcemia and calcium sensing receptor. Acta Clin Croat 2014; 53:220-5. Available from: https://hrcak.srce.hr/127693
Zahedi M, Hizomi Arani R, Rafati M, Amouzegar A, Hadaegh F. "Persistent hypercalcemia with similar familial Hypocalciuric hypercalcemia features: a case report and literature review." BMC Endocrine Disorders 21. 2021: 1-5.Available from: https://doi.org/10.1186/s12902-021-00881-9
Christensen SE, Nissen PH, Vestergaard P, Mosekilde L. Familial hypocalciuric hypercalcaemia: a review. Curr Opin Endocrinol Diabetes Obes. 2011 Dec;18(6):359-70. Available from: https://doi.org/10.1097/med.0b013e32834c3c7c
Ghaznavi SA, NMA Saad and LE Donovan. "The biochemical profile of familial hypocalciuric hypercalcemia and primary hyperparathyroidism during pregnancy and lactation: two case reports and review of the literature." Case reports in endocrinology 2016.1. 2016: 2725486. Available from: https://doi.org/10.1155/2016/2725486
Alix Lilian and Pascal Guggenbuhl. "Familial hypocalciuric hypercalcemia associated with crystal deposition disease." Joint Bone Spine 82.1. 2015: 60-62. Available from: https://doi.org/10.1016/j.jbspin.2014.08.007
Marstrand SD, Tofteng CL, Jarløv A, Borgwardt L, Schwarz P. "Concomitant familial hypocalciuric hypercalcemia and single parathyroid adenoma: a case report." Journal of Medical Case Reports 15. 2021: 1-6. Available from: https://doi.org/10.1186/s13256-021-03051-6
Davies M, Klimiuk PS, Adams PH, Lumb GA, Large DM, Anderson DC. Familial hypocalciuric hypercalcaemia and acute pancreatitis." Br Med J (Clin Res Ed) 282.6269. 1981: 1023-1025. Available from: doi: https://doi.org/10.1136/bmj.282.6269.1023
Marx SJ. Familial hypocalciuric hypercalcemia. N Engl J Med 1980; 303:810-1. Available from: https://doi.org/10.1056/nejm198010023031409
Marx Stephen J. "Calcimimetic use in familial hypocalciuric hypercalcemia—a perspective in endocrinology." The Journal of Clinical Endocrinology & Metabolism 102.11. 2017: 3933-3936. Available from: https://doi.org/10.1210/jc.2017-01606
Cuny T, Romanet P, Goldsworthy M, Guérin C, Wilkin M, Roche P, Taïeb D. "Cinacalcet reverses short QT interval in familial hypocalciuric hypercalcemia type 1." The Journal of Clinical Endocrinology & Metabolism 109.2. 2024:549-556. Available from: https://doi.org/10.1210/clinem/dgad494
Anthonypillai J, Sinha SK, Mamkin A, Ten S, Dong Q, Bhangoo A. "Experience with cinacalcet in familial hypocalciuric hypercalcemia resulting from inactivating mutations in calcium sensing receptor (CaSR)." Endocrinol Metab Int J 6.2 (2018): 137-140. DOI: 10.15406/emij.2018.06.00167
Koca Serkan Bilge. "Cinacalcet therapy in a child with novel homozygous CASR p. Glu353Lys mutation causing familial hypocalciuric hypercalcemia type 1: case report and review of the literature." The Turkish Journal of Pediatrics 65.5. 2023:853-861. Available from: DOI: 10.24953/turkjped.2022.1040
Reddi Alluru S. "Disorders of Calcium: Hypercalcemia." Fluid, Electrolyte and Acid-Base Disorders: Clinical Evaluation and Management. Cham: Springer International Publishing. 2023:291-311. Available from: https://doi.org/10.1007/978-3-031-25810-7_19
Minisola S, Pepe J, Piemonte S, Cipriani C. "The diagnosis and management of hypercalcaemia." Bmj 350. 2015. Available from: doi: https://doi.org/10.1136/bmj.h2723.