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===='''Alkalosis'''====
===='''Alkalosis'''====
* In [[alkalosis]], [[hydrogen ion]]s dissociate from the negatively charged [[albumin]], which allows for increased calcium binding and leads to a decreased concentration of free calcium.
* In [[alkalosis]], [[hydrogen ion]]s dissociate from the negatively charged [[albumin]], which allows for increased calcium binding and leads to a decreased concentration of free [[calcium]].


* For an increase in pH of 0.1 unit, there is an approximately 0.05 mmol/L (0.1 mEq/L) fall in the serum level of ionized calcium.   
* For an increase in pH of 0.1 unit, there is an approximately 0.05 mmol/L (0.1 mEq/L) fall in the serum level of ionized [[calcium]].   


===='''Respiratory Alkalosis'''====
===='''Respiratory alkalosis'''====
* Reduced [[ionized]] [[calcium]] concentration and [[hypocapnia]] associated with [[hyperventilation]] may contribute to symptoms of [[vasoconstriction]] including [[lightheadedness]], [[fainting]], and [[paresthesia]].
* Reduced [[ionized]] [[calcium]] concentration and [[hypocapnia]] associated with [[hyperventilation]] may contribute to symptoms of [[vasoconstriction]] including [[lightheadedness]], [[fainting]], and [[paresthesia]].


===Globulin Binding===
===Globulin binding===
* [[Calcium]] binding to [[globulin]] is relatively small (1.0 g of globulin binds 0.2–0.3 mg of [[calcium]]) and generally does not influence the total serum calcium concentration.<ref>{{cite book | last = Taal | first = Maarten | title = Brenner & Rector's the kidney | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2012 | isbn = 978-1416061939 }}</ref>
* [[Calcium]] binding to [[globulin]] is relatively small (1.0 g of [[globulin]] binds 0.2–0.3 mg of [[calcium]]) and generally does not influence the total [[serum]] [[calcium]] concentration.<ref>{{cite book | last = Taal | first = Maarten | title = Brenner & Rector's the kidney | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2012 | isbn = 978-1416061939 }}</ref>


=== Autoimmune ===
=== Autoimmune ===
* [[Hypoparathyroidism]] which is [[acquired]] but not related to any [[surgery]] is most often an [[autoimmune disease]].<ref name="pmid3332555">{{cite journal |vauthors=Posillico JT, Wortsman J, Srikanta S, Eisenbarth GS, Mallette LE, Brown EM |title=Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells |journal=J. Bone Miner. Res. |volume=1 |issue=5 |pages=475–83 |date=October 1986 |pmid=3332555 |doi=10.1002/jbmr.5650010512 |url=}}</ref>  
* [[Hypoparathyroidism]] which is [[acquired]] but not related to any [[surgery]] is most often an [[autoimmune disease]].<ref name="pmid3332555">{{cite journal |vauthors=Posillico JT, Wortsman J, Srikanta S, Eisenbarth GS, Mallette LE, Brown EM |title=Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells |journal=J. Bone Miner. Res. |volume=1 |issue=5 |pages=475–83 |date=October 1986 |pmid=3332555 |doi=10.1002/jbmr.5650010512 |url=}}</ref>  
* [[Autoimmune]] destruction of parathyroid glands results in permanent [[hypoparathyroidism]] .  
* [[Autoimmune]] destruction of [[parathyroid glands]] results in permanent [[hypoparathyroidism]] .  


== Genetics ==
== Genetics ==
The development of [[hypocalcemia]] is the result of genetic [[Mutation|mutations]] such as
The development of [[hypocalcemia]] is the result of genetic [[Mutation|mutations]] such as
* [[Mutations]] in the [[Transcription (genetics)|transcription]] factor glial-cell missing B (GCMB).  
* [[Mutations]] in the [[Transcription (genetics)|transcription]] factor [[Glial cell|glial-cell]] missing B (GCMB).  
* Mutations in the [[calcium-sensing receptor]], results in [[autosomal dominant]] [[hypocalcemia]] (ADH).which is of 2 types<ref name="pmid8733126">{{cite journal |vauthors=Baron J, Winer KK, Yanovski JA, Cunningham AW, Laue L, Zimmerman D, Cutler GB |title=Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism |journal=Hum. Mol. Genet. |volume=5 |issue=5 |pages=601–6 |date=May 1996 |pmid=8733126 |doi= |url=}}</ref><ref name="pmid11152759">{{cite journal |vauthors=Brown EM, MacLeod RJ |title=Extracellular calcium sensing and extracellular calcium signaling |journal=Physiol. Rev. |volume=81 |issue=1 |pages=239–297 |date=January 2001 |pmid=11152759 |doi=10.1152/physrev.2001.81.1.239 |url=}}</ref><ref name="pmid28176280">{{cite journal |vauthors=Szalat A, Shpitzen S, Tsur A, Zalmon Koren I, Shilo S, Tripto-Shkolnik L, Durst R, Leitersdorf E, Meiner V |title=Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia |journal=Endocrine |volume=55 |issue=3 |pages=741–747 |date=March 2017 |pmid=28176280 |doi=10.1007/s12020-017-1241-5 |url=}}</ref>
* Mutations in the [[calcium-sensing receptor]], results in [[autosomal dominant]] [[hypocalcemia]] (ADH).which is of 2 types<ref name="pmid8733126">{{cite journal |vauthors=Baron J, Winer KK, Yanovski JA, Cunningham AW, Laue L, Zimmerman D, Cutler GB |title=Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism |journal=Hum. Mol. Genet. |volume=5 |issue=5 |pages=601–6 |date=May 1996 |pmid=8733126 |doi= |url=}}</ref><ref name="pmid11152759">{{cite journal |vauthors=Brown EM, MacLeod RJ |title=Extracellular calcium sensing and extracellular calcium signaling |journal=Physiol. Rev. |volume=81 |issue=1 |pages=239–297 |date=January 2001 |pmid=11152759 |doi=10.1152/physrev.2001.81.1.239 |url=}}</ref><ref name="pmid28176280">{{cite journal |vauthors=Szalat A, Shpitzen S, Tsur A, Zalmon Koren I, Shilo S, Tripto-Shkolnik L, Durst R, Leitersdorf E, Meiner V |title=Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia |journal=Endocrine |volume=55 |issue=3 |pages=741–747 |date=March 2017 |pmid=28176280 |doi=10.1007/s12020-017-1241-5 |url=}}</ref>
** Type 1: [[Autosomal dominant]] [[hypocalcemia]] (ADH) 1 is due to activating mutation in the CaSR.<ref name="pmid9253358">{{cite journal |vauthors=De Luca F, Ray K, Mancilla EE, Fan GF, Winer KK, Gore P, Spiegel AM, Baron J |title=Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor |journal=J. Clin. Endocrinol. Metab. |volume=82 |issue=8 |pages=2710–5 |date=August 1997 |pmid=9253358 |doi=10.1210/jcem.82.8.4166 |url=}}</ref><ref name="pmid12915654">{{cite journal |vauthors=Hendy GN, Minutti C, Canaff L, Pidasheva S, Yang B, Nouhi Z, Zimmerman D, Wei C, Cole DE |title=Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue=8 |pages=3674–81 |date=August 2003 |pmid=12915654 |doi=10.1210/jc.2003-030409 |url=}}</ref><ref name="pmid10770217">{{cite journal |vauthors=Lienhardt A, Garabédian M, Bai M, Sinding C, Zhang Z, Lagarde JP, Boulesteix J, Rigaud M, Brown EM, Kottler ML |title=A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxylterminal cytoplasmic tail that causes autosomal dominant hypocalcemia |journal=J. Clin. Endocrinol. Metab. |volume=85 |issue=4 |pages=1695–702 |date=April 2000 |pmid=10770217 |doi=10.1210/jcem.85.4.6570 |url=}}</ref><ref name="pmid8698326">{{cite journal |vauthors=Løvlie R, Eiken HG, Sørheim JI, Boman H |title=The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism |journal=Hum. Genet. |volume=98 |issue=2 |pages=129–33 |date=August 1996 |pmid=8698326 |doi= |url=}}</ref>
** Type 1: [[Autosomal dominant]] [[hypocalcemia]] (ADH) 1 is due to activating mutation in the CaSR.<ref name="pmid9253358">{{cite journal |vauthors=De Luca F, Ray K, Mancilla EE, Fan GF, Winer KK, Gore P, Spiegel AM, Baron J |title=Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor |journal=J. Clin. Endocrinol. Metab. |volume=82 |issue=8 |pages=2710–5 |date=August 1997 |pmid=9253358 |doi=10.1210/jcem.82.8.4166 |url=}}</ref><ref name="pmid12915654">{{cite journal |vauthors=Hendy GN, Minutti C, Canaff L, Pidasheva S, Yang B, Nouhi Z, Zimmerman D, Wei C, Cole DE |title=Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue=8 |pages=3674–81 |date=August 2003 |pmid=12915654 |doi=10.1210/jc.2003-030409 |url=}}</ref><ref name="pmid10770217">{{cite journal |vauthors=Lienhardt A, Garabédian M, Bai M, Sinding C, Zhang Z, Lagarde JP, Boulesteix J, Rigaud M, Brown EM, Kottler ML |title=A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxylterminal cytoplasmic tail that causes autosomal dominant hypocalcemia |journal=J. Clin. Endocrinol. Metab. |volume=85 |issue=4 |pages=1695–702 |date=April 2000 |pmid=10770217 |doi=10.1210/jcem.85.4.6570 |url=}}</ref><ref name="pmid8698326">{{cite journal |vauthors=Løvlie R, Eiken HG, Sørheim JI, Boman H |title=The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism |journal=Hum. Genet. |volume=98 |issue=2 |pages=129–33 |date=August 1996 |pmid=8698326 |doi= |url=}}</ref>
*** This [[mutation]] leads in shifting the set points of CaSR which results in no [[Parathyroid hormone|PTH]] release with altered changes in the levels of serum [[calcium]].   
*** This [[mutation]] leads in shifting the set points of CaSR which results in no [[Parathyroid hormone|PTH]] release with altered changes in the levels of serum [[calcium]].   
** Type 2: [[Autosomal dominant]] hypocalcemia ([[ADH]]) 2 is due to activating mutation in the [[guanine]] [[nucleotide]] binding protein, alpha 11 gene(''GNA11)''.<ref name="pmid24823460">{{cite journal |vauthors=Li D, Opas EE, Tuluc F, Metzger DL, Hou C, Hakonarson H, Levine MA |title=Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization |journal=J. Clin. Endocrinol. Metab. |volume=99 |issue=9 |pages=E1774–83 |date=September 2014 |pmid=24823460 |pmc=4154081 |doi=10.1210/jc.2014-1029 |url=}}</ref><ref name="pmid23802516">{{cite journal |vauthors=Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, Rust N, Hobbs MR, Heath H, Thakker RV |title=Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia |journal=N. Engl. J. Med. |volume=368 |issue=26 |pages=2476–2486 |date=June 2013 |pmid=23802516 |pmc=3773604 |doi=10.1056/NEJMoa1300253 |url=}}</ref>
** Type 2: [[Autosomal dominant]] hypocalcemia ([[ADH]]) 2 is due to activating [[mutation]] in the [[guanine]] [[nucleotide]] binding [[protein]], alpha 11 [[gene]](''GNA11)''.<ref name="pmid24823460">{{cite journal |vauthors=Li D, Opas EE, Tuluc F, Metzger DL, Hou C, Hakonarson H, Levine MA |title=Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization |journal=J. Clin. Endocrinol. Metab. |volume=99 |issue=9 |pages=E1774–83 |date=September 2014 |pmid=24823460 |pmc=4154081 |doi=10.1210/jc.2014-1029 |url=}}</ref><ref name="pmid23802516">{{cite journal |vauthors=Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, Rust N, Hobbs MR, Heath H, Thakker RV |title=Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia |journal=N. Engl. J. Med. |volume=368 |issue=26 |pages=2476–2486 |date=June 2013 |pmid=23802516 |pmc=3773604 |doi=10.1056/NEJMoa1300253 |url=}}</ref>
*** This [[mutation]] leads to [[Downstream (molecular biology)|downstream]] CaSR signaling.  
*** This [[mutation]] leads to [[Downstream (molecular biology)|downstream]] CaSR signaling.  


Latest revision as of 11:34, 13 August 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]

Overview

Hypocalcemia may develop in disorders associated with insufficient parathyroid hormone or vitamin D production or resistance to hormonal activities. Perturbations of calcium homeostasis can be caused by environmental factors or occur as a result of genetic mutations in the calcium-sensing receptor (as in type 1 autosomal dominant hypocalcemia), Gs α subunit (as in type 1A and 1B pseudohypoparathyroidism), vitamin D hydroxylase (as in type 1 vitamin D-dependent rickets , and calcitriol receptor (as in type 2 vitamin D-dependent rickets).

Pathophysiology

Physiology

The normal physiology of Hypocalcemia can be understood as follows:[1][2]

  • The normal concentrations of calcium in the body is maintained within the narrow range and that is required for the optimal activity of the many extra- and intracellular processes that calcium regulates. 
  • Calcium transport within the blood is mainly via bound to plasma proteins such as albumin (45%), phosphate and citrate (15%) and ionized state (40%).
  • Only the ionized form of calcium is active but most laboratories show report of total serum calcium concentrations.
  • The normal concentration of calcium ranges between 8.5 and 10.5 mg/dL.
  • The normal range of ionized calcium in the plasma is 4.65 to 5.25 mg/dL.

Pathogenesis

It is understood that hypocalcemia may result through any of the following mechanisms:

Vitamin D deficiency

Hypoalbuminemia

  • When there is a fluctuation in serum protein concentrations, especially albumin, total calcium levels in the blood may change.[5][6]
  • Whereas the levels of ionized calcium (free form) remains mostly constant, because it is hormonally regulated.
  • In cases of hypoalbuminemia, total serum calcium levels may not accurately reflect the physiologically important ionized calcium concentration.
  • Therefore, a correction may be required in order to arrive at the corrected calcium levels. (Corrected calcium = Measured calcium + 0.02 x [40 - Albumin])

Hormonal regulation 

Magnesium 

Acid-base disturbances

Alkalosis

  • For an increase in pH of 0.1 unit, there is an approximately 0.05 mmol/L (0.1 mEq/L) fall in the serum level of ionized calcium.

Respiratory alkalosis

Globulin binding

Autoimmune 

Genetics

The development of hypocalcemia is the result of genetic mutations such as

References

  1. ↑ Fong J, Khan A (February 2012). "Hypocalcemia: updates in diagnosis and management for primary care". Can Fam Physician. 58 (2): 158–62. PMC 3279267. PMID 22439169.
  2. ↑ Carroll R, Matfin G (February 2010). "Endocrine and metabolic emergencies: hypocalcaemia". Ther Adv Endocrinol Metab. 1 (1): 29–33. doi:10.1177/2042018810366494. PMC 3474611. PMID 23148147.
  3. ↑ Carroll R, Matfin G (February 2010). "Endocrine and metabolic emergencies: hypocalcaemia". Ther Adv Endocrinol Metab. 1 (1): 29–33. doi:10.1177/2042018810366494. PMC 3474611. PMID 23148147.
  4. ↑ Papapoulos SE, Harinck HI, Bijvoet OL, Gleed JH, Fraher LJ, O'Riordan JL (February 1986). "Effects of decreasing serum calcium on circulating parathyroid hormone and vitamin D metabolites in normocalcaemic and hypercalcaemic patients treated with APD". Bone Miner. 1 (1): 69–78. PMID 3508718.
  5. ↑ Fong J, Khan A (February 2012). "Hypocalcemia: updates in diagnosis and management for primary care". Can Fam Physician. 58 (2): 158–62. PMC 3279267. PMID 22439169.
  6. ↑ Carroll R, Matfin G (February 2010). "Endocrine and metabolic emergencies: hypocalcaemia". Ther Adv Endocrinol Metab. 1 (1): 29–33. doi:10.1177/2042018810366494. PMC 3474611. PMID 23148147.
  7. ↑ Riccardi D, Brown EM (March 2010). "Physiology and pathophysiology of the calcium-sensing receptor in the kidney". Am. J. Physiol. Renal Physiol. 298 (3): F485–99. doi:10.1152/ajprenal.00608.2009. PMC 2838589. PMID 19923405.
  8. ↑ Goodman WG (January 2004). "Calcium-sensing receptors". Semin. Nephrol. 24 (1): 17–24. PMID 14730506.
  9. ↑ Quarles LD (July 2003). "Extracellular calcium-sensing receptors in the parathyroid gland, kidney, and other tissues". Curr. Opin. Nephrol. Hypertens. 12 (4): 349–55. doi:10.1097/01.mnh.0000079682.89474.80. PMID 12815330.
  10. ↑ Toka HR, Pollak MR (September 2014). "The role of the calcium-sensing receptor in disorders of abnormal calcium handling and cardiovascular disease". Curr. Opin. Nephrol. Hypertens. 23 (5): 494–501. doi:10.1097/MNH.0000000000000042. PMID 24992569.
  11. ↑ Egbuna OI, Brown EM (March 2008). "Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor mutations". Best Pract Res Clin Rheumatol. 22 (1): 129–48. doi:10.1016/j.berh.2007.11.006. PMC 2364635. PMID 18328986.
  12. ↑ Blaine J, Chonchol M, Levi M (July 2015). "Renal control of calcium, phosphate, and magnesium homeostasis". Clin J Am Soc Nephrol. 10 (7): 1257–72. doi:10.2215/CJN.09750913. PMC 4491294. PMID 25287933.
  13. ↑ Akerström G, Hellman P, Hessman O, Segersten U, Westin G (April 2005). "Parathyroid glands in calcium regulation and human disease". Ann. N. Y. Acad. Sci. 1040: 53–8. doi:10.1196/annals.1327.005. PMID 15891005.
  14. ↑ Carroll R, Matfin G (February 2010). "Endocrine and metabolic emergencies: hypocalcaemia". Ther Adv Endocrinol Metab. 1 (1): 29–33. doi:10.1177/2042018810366494. PMC 3474611. PMID 23148147.
  15. ↑ Carrillo-López N, Fernández-Martín JL, Cannata-Andía JB (2009). "[The role of calcium, calcitriol and their receptors in parathyroid regulation]". Nefrologia (in Spanish; Castilian). 29 (2): 103–8. doi:10.3265/Nefrologia.2009.29.2.5154.en.full. PMID 19396314.
  16. ↑ Wu X, Sonnenberg H (November 1995). "Effect of renal perfusion pressure on excretion of calcium, magnesium, and phosphate in the rat". Clin. Exp. Hypertens. 17 (8): 1269–85. PMID 8563701.
  17. ↑ Mortensen L, Hyldstrup L, Charles P (January 1997). "Effect of vitamin D treatment in hypoparathyroid patients: a study on calcium, phosphate and magnesium homeostasis". Eur. J. Endocrinol. 136 (1): 52–60. PMID 9037127.
  18. ↑ Poole, K; Reeve, J (2005). "Parathyroid hormone — a bone anabolic and catabolic agent". Current Opinion in Pharmacology. 5 (6): 612–617. doi:10.1016/j.coph.2005.07.004. ISSN 1471-4892.
  19. ↑ Cholst IN, Steinberg SF, Tropper PJ, Fox HE, Segre GV, Bilezikian JP (May 1984). "The influence of hypermagnesemia on serum calcium and parathyroid hormone levels in human subjects". N. Engl. J. Med. 310 (19): 1221–5. doi:10.1056/NEJM198405103101904. PMID 6709029.
  20. ↑ van den Bergh WM, van de Water JM, Hoff RG, Algra A, Rinkel GJ (2008). "Calcium homeostasis during magnesium treatment in aneurysmal subarachnoid hemorrhage". Neurocrit Care. 8 (3): 413–7. doi:10.1007/s12028-008-9068-9. PMID 18317951.
  21. ↑ Kido Y, Okamura T, Tomikawa M, Yamamoto M, Shiraishi M, Okada Y, Kimura T, Sugimachi K (October 1996). "Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients with advanced colorectal or gastric carcinomas". Cancer. 78 (8): 1794–7. PMID 8859194.
  22. ↑ Kido Y, Okamura T, Tomikawa M, Yamamoto M, Shiraishi M, Okada Y, Kimura T, Sugimachi K (October 1996). "Hypocalcemia associated with 5-fluorouracil and low dose leucovorin in patients with advanced colorectal or gastric carcinomas". Cancer. 78 (8): 1794–7. PMID 8859194.
  23. ↑ Taal, Maarten (2012). Brenner & Rector's the kidney. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1416061939.
  24. ↑ Posillico JT, Wortsman J, Srikanta S, Eisenbarth GS, Mallette LE, Brown EM (October 1986). "Parathyroid cell surface autoantibodies that inhibit parathyroid hormone secretion from dispersed human parathyroid cells". J. Bone Miner. Res. 1 (5): 475–83. doi:10.1002/jbmr.5650010512. PMID 3332555.
  25. ↑ Baron J, Winer KK, Yanovski JA, Cunningham AW, Laue L, Zimmerman D, Cutler GB (May 1996). "Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism". Hum. Mol. Genet. 5 (5): 601–6. PMID 8733126.
  26. ↑ Brown EM, MacLeod RJ (January 2001). "Extracellular calcium sensing and extracellular calcium signaling". Physiol. Rev. 81 (1): 239–297. doi:10.1152/physrev.2001.81.1.239. PMID 11152759.
  27. ↑ Szalat A, Shpitzen S, Tsur A, Zalmon Koren I, Shilo S, Tripto-Shkolnik L, Durst R, Leitersdorf E, Meiner V (March 2017). "Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia". Endocrine. 55 (3): 741–747. doi:10.1007/s12020-017-1241-5. PMID 28176280.
  28. ↑ De Luca F, Ray K, Mancilla EE, Fan GF, Winer KK, Gore P, Spiegel AM, Baron J (August 1997). "Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor". J. Clin. Endocrinol. Metab. 82 (8): 2710–5. doi:10.1210/jcem.82.8.4166. PMID 9253358.
  29. ↑ Hendy GN, Minutti C, Canaff L, Pidasheva S, Yang B, Nouhi Z, Zimmerman D, Wei C, Cole DE (August 2003). "Recurrent familial hypocalcemia due to germline mosaicism for an activating mutation of the calcium-sensing receptor gene". J. Clin. Endocrinol. Metab. 88 (8): 3674–81. doi:10.1210/jc.2003-030409. PMID 12915654.
  30. ↑ Lienhardt A, Garabédian M, Bai M, Sinding C, Zhang Z, Lagarde JP, Boulesteix J, Rigaud M, Brown EM, Kottler ML (April 2000). "A large homozygous or heterozygous in-frame deletion within the calcium-sensing receptor's carboxylterminal cytoplasmic tail that causes autosomal dominant hypocalcemia". J. Clin. Endocrinol. Metab. 85 (4): 1695–702. doi:10.1210/jcem.85.4.6570. PMID 10770217.
  31. ↑ Løvlie R, Eiken HG, Sørheim JI, Boman H (August 1996). "The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism". Hum. Genet. 98 (2): 129–33. PMID 8698326.
  32. ↑ Li D, Opas EE, Tuluc F, Metzger DL, Hou C, Hakonarson H, Levine MA (September 2014). "Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization". J. Clin. Endocrinol. Metab. 99 (9): E1774–83. doi:10.1210/jc.2014-1029. PMC 4154081. PMID 24823460.
  33. ↑ Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, Rust N, Hobbs MR, Heath H, Thakker RV (June 2013). "Mutations affecting G-protein subunit α11 in hypercalcemia and hypocalcemia". N. Engl. J. Med. 368 (26): 2476–2486. doi:10.1056/NEJMoa1300253. PMC 3773604. PMID 23802516.

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