Hereditary syndromal and nonsyndromal forms of primary hyperparathyroidism

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract


Primary hyperparathyroidism is a common disorder of mineral homeostasis, characterized by overproduction of parathyroid hormone and upper normal or elevated calcium levels due to hyperplasia or a tumor of parathyroid gland. 90−95% of cases of primary hyperparathyroidism are sporadic, while hereditary genetic forms occur in 5–10% of all cases. Primary hyperparathyroidism as the component of hereditary syndromes can present in various clinical forms (asymptomatic, symptomatic), can be associated with other endocrine or non-endocrine diseases, and require special approaches to treatment. Given that primary hyperparathyroidism is one of the most common components of these syndromes, it can be used as an important diagnostic tool in identifying affected families. This review is devoted to modern ideas about the clinical course and genetic characteristics of hereditary variants of primary hyperparathyroidism and the diagnostic and treatment algorithms recommended today. The review considers primary hyperparathyroidism as a component of hereditary syndromes including multiple endocrine neoplasias types 1, 2A and 4 and syndrome of hyperparathyroidism with a jaw tumor. Also non-syndromic hereditary forms are descripted, such as familial isolated hyperparathyroidism, familial hypocalciuric hypercalcemia, and severe neonatal primary hyperparathyroidism.


Full Text

Restricted Access

About the authors

Anna M. Gorbacheva

Endocrinology Research Centre

Author for correspondence.
Email: ann.gorbachewa@yandex.ru
ORCID iD: 0000-0003-2669-9457
SPIN-code: 9815-7509
Scopus Author ID: 57190977461
ResearcherId: F-2798-2018

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD

Anna K. Eremkina

Endocrinology Research Centre

Email: eremkina.anna@endocrincentr.ru
ORCID iD: 0000-0001-6667-062X
SPIN-code: 8848-2660

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD

Natalya G. Mokrysheva

Endocrinology research centre

Email: nm70@mail.ru
ORCID iD: 0000-0002-9717-9742
SPIN-code: 5624-3875

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD, Professor

References

  1. Marcocci C, Cetani F. Clinical practice. Primary hyperparathyroidism. N Engl J Med. 2011;365(25):2389–2397. doi: https://doi.org/10.1056/NEJMcp1106636
  2. Cetani F, Saponaro F, Borsari S, Marcocci C. Familial and hereditary forms of primary hyperparathyroidism. Front Horm Res. 2019;51:40–51. doi: https://doi.org/10.1159/000491037
  3. Brandi ML, Gagel RF, Angeli A, et al. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–5671. doi: https://doi.org/10.1210/jcem.86.12.8070
  4. Thakker RV. Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4). Mol Cell Endocrinol. 2014;386(1-2):2–15. doi: https://doi.org/10.1016/j.mce.2013.08.002
  5. Iacobone M, Carnaille B, Palazzo FF, Vriens M. Hereditary hyperparathyroidism — a consensus report of the european society of endocrine surgeons (ESES). Langenbecks Arch Surg. 2015;400(8):867–886. doi: https://doi.org/10.1007/s00423-015-1342-7
  6. Huang J, Gurung B, Wan B, et al. The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature. 2012;482(7386):542–546. doi: https://doi.org/10.1038/nature10806
  7. Wu T, Hua X. Menin represses tumorigenesis via repressing cell proliferation. Am J Cancer Res. 2011;1(6):726–739.
  8. Giusti F, Cianferotti L, Boaretto F, et al. Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database. Endocrine. 2017;58(2):349–359. doi: https://doi.org/10.1007/s12020-017-1234-4
  9. Pardi E, Borsari S, Saponaro F, et al. Mutational and large deletion study of genes implicated in hereditary forms of primary hyperparathyroidism and correlation with clinical features. PLoS One. 2017;12(10):e0186485. doi: https://doi.org/10.1371/journal.pone.0186485
  10. Thevenon J, Bourredjem A, Faivre L, et al. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d’etude des Tumeurs Endocrines (GTE) cohort study. Hum Mol Genet. 2013;22(10):1940–1948. doi: https://doi.org/10.1093/hmg/ddt039
  11. Bartsch DK, Slater EP, Albers M, et al. Higher risk of aggressive pancreatic neuroendocrine tumors in MEN1 patients with MEN1 mutations affecting the CHES1 interacting MENIN domain. J Clin Endocrinol Metab. 2014;99(11):E2387–2391. doi: https://doi.org/10.1210/jc.2013-4432
  12. Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990–3011. doi: https://doi.org/10.1210/jc.2012-1230
  13. Дедов И.И., Мельниченко Г.А., Мокрышева Н.Г., и др. Первичный гиперпаратиреоз: клиника, диагностика, дифференциальная диагностика, методы лечения // Проблемы эндокринологии. — 2016. — Т.62. — №6. — С. 40–77. [Dedov II, Melnichenko GA, Mokrysheva NG, et al. Primary hyperparathyroidism: the clinical picture, diagnostics, differential diagnostics, and methods of treatment. Problems of endocrinology. 2016;62(6):40–77. (In Russ).] doi: 10.14341/probl201662640-77
  14. Wu Y, Gao L, Guo X, et al. Pituitary adenomas in patients with multiple endocrine neoplasia type 1: a single-center experience in China. Pituitary. 2019;22(2):113–123. doi: https://doi.org/10.1007/s11102-019-00939-x
  15. Vergès B, Boureille F, Goudet P, et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87(2):457–465. doi: https://doi.org/10.1210/jcem.87.2.8145
  16. Jensen RT, Norton JA. Treatment of pancreatic neuroendocrine tumors in multiple endocrine neoplasia Type 1: some clarity but continued controversy. Pancreas. 2017;46(5):589–594. doi: https://doi.org/10.1097/MPA.0000000000000825
  17. Eller-Vainicher C, Chiodini I, Battista C, et al. Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity. J Bone Miner Res. 2009;24(8):1404–1410. doi: https://doi.org/10.1359/jbmr.090304
  18. Schaaf L, Pickel J, Zinner K, et al. Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1. Exp Clin Endocrinol Diabetes. 2007;115(8):509–517. doi: https://doi.org/10.1055/s-2007-970160
  19. Goudet P, Dalac A, Le Bras M, et al. MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d’étude des tumeurs endocrines. J Clin Endocrinol Metab. 2015;100(4):1568–1577. doi: https://doi.org/10.1210/jc.2014-3659
  20. Мамедова Е.О., Мокрышева Н.Г., Пигарова Е.А., и др. Молекулярно-генетические особенности первичного гиперпаратиреоза у пациентов молодого возраста // Проблемы эндокринологии. — 2016. — Т.62. — №2. — С. 4–11. [Mamedova EO, Mokrysheva NG, Pigarova EA, et al. Molecular and genetic features of primary hyperparathyroidism in young patients. Problems of endocrinology. 2016;62(2):4–11. (In Russ).] doi: 10.14341/probl20166224-11
  21. Ростомян Л.Г. Синдром множественных эндокринных неоплазий 1 типа: распространенность среди пациентов с первичным гиперпаратиреозом, клинические и молекулярно-генетические характеристики: Автореф. дис. … канд. мед. наук. — М., 2011. — 22 с. [Rostomyan LG. Sindrom mnozhestvennykh endokrinnykh neoplazii 1 tipa: rasprostranennost’ sredi patsientov s pervichnym giperparatireozom, klinicheskie i molekulyarno-geneticheskie kharakteristiki. [dissertation abstract] Moscow; 2011. 22 р. (In Russ).] Доступно по: https://search.rsl.ru/ru/record/01004856663. Ссылка активна на 21.02.2020.
  22. Keutgen XM, Nilubol N, Agarwal S, et al. Reoperative surgery in patients with multiple endocrine neoplasia type 1 associated primary hyperparathyroidism. Ann Surg Oncol. 2016;23(Suppl 5):701–707. doi: 10.1245/s10434-016-5467-x.
  23. Skandarajah A, Barlier A, Morlet-Barlat N, et al. Should routine analysis of the MEN1 gene be performed in all patients with primary hyperparathyroidism under 40 years of age? World J Surg. 2010;34(6):1294–1298. doi: https://doi.org/10.1007/s00268-009-0388-5
  24. Starker LF, Akerström T, Long WD, et al. Frequent germ-line mutations of the MEN1, CASR, and HRPT2/CDC73 genes in young patients with clinically non-familial primary hyperparathyroidism. Horm Cancer. 2012;3(1-2):44–51. doi: https://doi.org/10.1007/s12672-011-0100-8
  25. Roijers JF, de Wit MJ, van der Luijt RB, et al. Criteria for mutation analysis in MEN 1-suspected patients: MEN 1 case-finding. Eur J Clin Invest. 2000;30(6):487–492. doi: https://doi.org/10.1046/j.1365-2362.2000.00664.x
  26. Cardinal JW, Bergman L, Hayward N, et al. A report of a national mutation testing service for the MEN1 gene: clinical presentations and implications for mutation testing. J Med Genet. 2005;42(1):69–74. doi: 10.1136/jmg.2003.017319
  27. Lairmore TC, Piersall LD, DeBenedetti MK, et al. Clinical genetic testing and early surgical intervention in patients with multiple endocrine neoplasia type 1 (MEN 1). Ann Surg. 2004;239(5):637–645. doi: 10.1097/01.sla.0000124383.98416.8d
  28. Goudet P, Murat A, Binquet C, et al. Risk factors and causes of death in MEN1 disease. A GTE (groupe d’etude des tumeurs endocrines) cohort study among 758 patients. World J Surg. 2010;34(2):249–255. doi: https://doi.org/10.1007/s00268-009-0290-1
  29. Twigt BA, Scholten A, Valk GD, et al. Differences between sporadic and MEN related primary hyperparathyroidism; clinical expression, preoperative workup, operative strategy and follow-up. Orphanet J Rare Dis. 2013;8:50. doi: https://doi.org/10.1186/1750-1172-8-50
  30. Pieterman CR, van Hulsteijn LT, den Heijer M, et al. Primary hyperparathyroidism in MEN1 patients: a cohort study with longterm follow-up on preferred surgical procedure and the relation with genotype. Ann Surg. 2012;255(6):1171−1178. doi: https://doi.org/10.1097/SLA.0b013e31824c5145
  31. Lairmore TC, Govednik CM, Quinn CE, et al. A randomized, prospective trial of operative treatments for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery. 2014;156(6):1326–1334. doi: https://doi.org/10.1016/j.surg.2014.08.006
  32. Elaraj DM, Skarulis MC, Libutti SK, et al. Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Surgery. 2003;134(6):858–864. doi: https://doi.org/10.1016/s0039-6060(03)00406-9
  33. Schreinemakers JM, Pieterman CR, Scholten A, et al. The optimal surgical treatment for primary hyperparathyroidism in MEN1 patients: a systematic review. World J Surg. 2011;35(9):1993–2005. doi: https://doi.org/10.1007/s00268-011-1068-9
  34. Lambert LA, Shapiro SE, Lee JE, et al. Surgical treatment of hyperparathyroidism in patients with multiple endocrine neoplasia type 1. Arch Surg. 2005;140(4):374–382. doi: 10.1001/archsurg.140.4.374
  35. Salmeron MD, Gonzalez JM, Sancho Insenser J, et al. Causes and treatment of recurrent hyperparathyroidism after subtotal parathyroidectomy in the presence of multiple endocrine neoplasia 1. World J Surg. 2010;34(6):1325–1331. doi: https://doi.org/10.1007/s00268-010-0605-2
  36. Goudet P, Cougard P, Vergès B, et al. Hyperparathyroidism in multiple endocrine neoplasia type I: surgical trends and results of a 256-patient series from groupe d’etude des néoplasies endocriniennes multiples study group. World J Surg. 2001;25(7):886–890. doi: https://doi.org/10.1007/s00268-001-0046-z
  37. Balsalobre Salmeron M, Rodriguez Gonzalez JM, Ríos A, et al. Primary hyperparathyroidism associated with MEN 1: Experience in 71 cases. Cir Esp. 2018;96(10):627–633. doi: https://doi.org/10.1016/j.ciresp.2018.06.014
  38. Powell AC, Alexander HR, Pingpank JF, et al. The utility of routine transcervical thymectomy for multiple endocrine neoplasia 1-related hyperparathyroidism. Surgery. 2008;144(6):878–883. doi: https://doi.org/10.1016/j.surg.2008.08.031
  39. Versnick M, Popadich A, Sidhu S, et al. Minimally invasive parathyroidectomy provides a conservative surgical option for multiple endocrine neoplasia type 1-primary hyperparathyroidism. Surgery. 2013;154(1):101–105. doi: https://doi.org/10.1016/j.surg.2013.03.004
  40. Мокрышева Н.Г., Еремкина А.К., Ковалева Е.В. Гипопаратиреоз: этиология, клиническая картина, современные методы диагностики и лечения // Альманах клинической медицины. — 2016. — Т.44. — №4. — С. 477–492. [Mokrysheva NG, Eremkina AK, Kovaleva EV. Hypoparathyroidism: etiology, clinical manifestation, current diagnostics and treatment. Almanac of clinical mediciney. 2016;44(4):477–492. (In Russ).] doi: 10.18786/2072-0505-2016-44-4-477-492
  41. Saponaro F, Faggiano A, Grimaldi F, et al. Cinacalcet in the management of primary hyperparathyroidism: post marketing experience of an Italian multicentre group. Clin Endocrinol (Oxf). 2013;79(1):20–26. doi: https://doi.org/10.1111/cen.12108
  42. Giusti F, Cianferotti L, Gronchi G, et al. Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to Multiple Endocrine Neoplasia Syndrome type 1 (MEN1). Endocrine. 2016;52(3):495–506. doi: https://doi.org/10.1007/s12020-015-0696-5
  43. Romei C, Pardi E, Cetani F, Elisei R. Genetic and clinical features of multiple endocrine neoplasia types 1 and 2. J Oncol. 2012;2012:705036. doi: https://doi.org/10.1155/2012/705036
  44. Giusti F, Cavalli L, Cavalli T, Brandi ML. Hereditary hyperparathyroidism syndromes. J Clin Densitom. 2013;16(1):69–74. doi: https://doi.org/10.1016/j.jocd.2012.11.003
  45. Romei C, Ciampi R, Elisei R. A comprehensive overview of the role of the RET proto-oncogene in thyroid carcinoma. Nat Rev Endocrinol. 2016;12(4):192–202. doi: https://doi.org/10.1038/nrendo.2016.11
  46. Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. doi: https://doi.org/10.1089/thy.2014.0335
  47. Haddad RI, Nasr C, Bischoff L, et al. NCCN guidelines insights: thyroid carcinoma, version 2.2018. Thyroid. 2015;25(6):567–610. doi: https://doi.org/10.1089/thy.2014.0335
  48. Tonelli F, Marcucci T, Giudici F, et al. Surgical approach in hereditary hyperparathyroidism. Endocr J. 2009;56(7):827–841. doi: https://doi.org/10.1507/endocrj.k09e-204
  49. Moley JF, Skinner M, Gillanders WE, et al. Management of the parathyroid glands during preventive thyroidectomy in patients with multiple endocrine neoplasia type 2. Ann Surg. 2015;262(4):641–646. doi: https://doi.org/10.1097/SLA.0000000000001464
  50. Pellegata NS, Quintanilla-Martinez L, Siggelkow H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci U S A. 2006;103(42):15558–15563. doi: 10.1073/pnas.0603877103
  51. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1–133. doi: https://doi.org/10.1089/thy.2015.0020
  52. Alevizaki M, Stratakis CA. Multiple endocrine neoplasias: advances and challenges for the future. J Intern Med. 2009;266(1):1–4. doi: https://doi.org/10.1111/j.1365-2796.2009.02108.x
  53. Agarwal SK, Mateo CM, Marx SJ. Rare germline mutations in cyclin-dependent kinase inhibitor genes in multiple endocrine neoplasia type 1 and related states. J Clin Endocrinol Metab. 2009;94(5):1826–1834. doi: https://doi.org/10.1210/jc.2008-2083
  54. Georgitsi M, Raitila A, Karhu A, et al. Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. J Clin Endocrinol Metab. 2007;92(8):3321–3325. doi: 10.1210/jc.2006-2843
  55. Molatore S, Marinoni I, Lee M, et al. A novel germline CDKN1B mutation causing multiple endocrine tumors: clinical, genetic and functional characterization. Hum Mutat. 2010;31(11):E1825–835. doi: https://doi.org/10.1002/humu.21354
  56. de Laat JM, van der Luijt RB, Pieterman CR, et al. MEN1 redefined, a clinical comparison of mutation-positive and mutation-negative patients. BMC Med. 2016;14(1):182. doi: https://doi.org/10.1186/s12916-016-0708-1
  57. Lee M, Pellegata NS. Multiple endocrine neoplasia type 4. Front Horm Res. 2013;41:63–78. doi: https://doi.org/10.1159/000345670
  58. Crona J, Gustavsson T, Norlén O, et al. Somatic mutations and genetic heterogeneity at the CDKN1B locus in small intestinal neuroendocrine tumors. Ann Surg Oncol. 2015;22 Suppl 3:S1428–435. doi: https://doi.org/10.1245/s10434-014-4351-9
  59. Van der Tuin K, Tops CM, Adank MA, et al. CDC73-related disorders: clinical manifestations and case detection in primary hyperparathyroidism. J Clin Endocrinol Metab. 2017;102(12):4534–4540. doi: https://doi.org/10.1210/jc.2017-01249
  60. Мокрышева Н.Г., Крупинова Ю.А., Мирная С.С. Клинические и лабораторно-инструментальные возможности предоперационной диагностики рака околощитовидных желез // Эндокринная хирургия. — 2017. — Т.11. — №3. — С. 136–145. [Mokrysheva NG, Krupinova JA, Mirnaya SS. Clinical, laboratory and instrumental methods of pre-surgical diagnosis of the parathyroid glands cancer. Endocrine Surgery. 2017;11(3):136–145. (In Russ).] doi: 10.14341/serg20173136-145
  61. Kleihues P, Sobin LH. World Health Organization classification of tumors. Cancer. 2000;88(12):2887. doi: 10.1002/1097-0142(20000615)88:12<2887::aid-cncr32>3.0.co;2-f
  62. Iacobone M, Barzon L, Porzionato A, et al. The extent of parathyroidectomy for HRPT2-related hyperparathyroidism. Surgery. 2009;145(2):250–251. doi: https://doi.org/10.1016/j.surg.2008.06.027
  63. Iacobone M, Masi G, Barzon L, et al. Hyperparathyroidism-jaw tumor syndrome: a report of three large kindred. Langenbecks Arch Surg. 2009;394(5):817–825. doi: https://doi.org/10.1007/s00423-009-0511-y
  64. Rozhinskaya L, Pigarova E, Sabanova E, et al. Diagnosis and treatment challenges of parathyroid carcinoma in a 27-year-old woman with multiple lung metastases. Endocrinol Diabetes Metab Case Rep. 2017;2017. pii: 16–0113. doi: https://doi.org/10.1530/EDM-16-0113
  65. Schulte KM, Talat N, Galata G, et al. Oncologic resection achieving r0 margins improves disease-free survival in parathyroid cancer. Ann Surg Oncol. 2014;21(6):1891–1897. doi: https://doi.org/10.1245/s10434-014-3530-z
  66. Villar-del-Moral J, Jiménez-García A, Salvador-Egea P, et al. Prognostic factors and staging systems in parathyroid cancer: a multicenter cohort study. Surgery. 2014;156(5):1132–1144. doi: https://doi.org/10.1016/j.surg.2014.05.014.
  67. Hsu KT, Sippel RS, Chen H, Schneider DF. Is central lymph node dissection necessary for parathyroid carcinoma? Surgery. 2014;156(6):1336–1341. doi: https://doi.org/10.1016/j.surg.2014.08.005
  68. Guan B, Welch JM, Sapp JC, et al. GCM2-activating mutations in familial isolated hyperparathyroidism. Am J Hum Genet. 2016;99(5):1034–1044. doi: https://doi.org/10.1016/j.ajhg.2016.08.018
  69. Cardoso L, Stevenson M, Thakker RV. Molecular genetics of syndromic and non-syndromic forms of parathyroid carcinoma. Hum Mutat. 2017;38(12):1621–1648. doi: https://doi.org/10.1002/humu.23337
  70. Мокрышева Н.Г., Липатенкова А.К., Крупинова Ю.А. Рак околощитовидных желез: этиология, патогенез, клиническая картина, диагностика и лечение // Вестник РОНЦ им. Н.Н. Блохина РАМН. — 2016. — Т.27. — №3. — С. 45–54. [Mokrysheva NG, Lipatenkova AK, Krupinova YuA. Cancer parathyroid glands: etiology, pathogenesis, clinical presentation, diagnosis and treatment. Herald of N.N. Blokhin Cancer Research Center RAMS. 2016;27(3):45–54. (In Russ).]
  71. Kelly TG, Shattuck TM, Reyes-Mugica M, et al. Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation. J Bone Miner Res. 2006;21(10):1666–1671. doi: 10.1359/jbmr.060702
  72. Marx SJ. Letter to the editor: Distinguishing typical primary hyperparathyroidism from familial hypocalciuric hypercalcemia by using an index of urinary calcium. J Clin Endocrinol Metab. 2015;100(2):L29–30. doi: https://doi.org/10.1210/jc.2014-4221
  73. Firek AF, Kao PC, Heath H. Plasma intact parathyroid hormone (PTH) and PTH-related peptide in familial benign hypercalcemia: greater responsiveness to endogenous PTH than in primary hyperparathyroidism. J Clin Endocrinol Metab. 1991;72(3):541–546. doi: 10.1210/jcem-72-3-541
  74. Hannan FM, Babinsky VN, Thakker RV. Disorders of the calcium-sensing receptor and partner proteins: insights into the molecular basis of calcium homeostasis. J Mol Endocrinol. 2016;57(3):R127–142. doi: https://doi.org/10.1530/JME-16-0124
  75. Hannan FM, Thakker RV. Calcium-sensing receptor (CaSR) mutations and disorders of calcium, electrolyte and water metabolism. Best Pract Res Clin Endocrinol Metab. 2013;27(3):359–371. doi: https://doi.org/10.1016/j.beem.2013.04.007
  76. Nesbit MA, Hannan FM, Howles SA, et al. Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. Nat Genet. 2013;45(1):93–97. doi: https://doi.org/10.1038/ng.2492
  77. Murphy H, Patrick J, Báez-Irizarry E, et al. Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia. Eur J Med Genet. 2016;59(4):227–231. doi: https://doi.org/10.1016/j.ejmg.2016.02.001

Supplementary files

There are no supplementary files to display.

Statistics

Views

Abstract - 386

PDF (Russian) - 7

Cited-By


PlumX

Dimensions


Copyright (c) 2020 Gorbacheva A.M., Eremkina A.K., Mokrysheva N.G.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies