Hypoparathyroidism pathophysiology: Difference between revisions

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{{Hypoparathyroidism}}
{{Hypoparathyroidism}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{Anmol}}
==Overview==
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
Hypoparathyroidism is a decrease in [[serum]] [[parathyroid hormone]]. Normally, [[parathyroid hormone]] increases [[serum]] [[calcium]] and [[magnesium]] concentration, and decreases [[serum]] [[phosphate]] concentration. [[Secretion]] of [[parathyroid hormone]] from [[parathyroid gland]] is stimulated by [[Hypocalcemia|low serum calcium]]. [[Parathyroid glands]] have [[calcium]]-sensing receptors responsible for sensing [[extracellular]] ionized [[calcium]]. [[Calcium]] and [[magnesium]] provides a [[negative feedback]] for [[secretion]] of [[parathyroid hormone]]. Deficiency of [[parathyroid hormone]] causes body to decrease [[reabsorption]] of [[calcium]] from [[bone]], [[excretion]] of [[phosphate]], [[reabsorbtion]] of [[calcium]] from [[distal tubules]], and [[vitamin D]] mediated [[absorption]] of [[calcium]] from [[intestine]] leading to [[hypocalcemia]]. Many [[Genetic disorder|genetic conditions]] are associated with hypoparathyroidism. Hypoparathyroidism associated with [[genetic defects]] may be either [[autoimmune]] hypoparathyroidism, isolated hypoparathyroidism, associated with [[congenital]] multisystem syndromes, or a part of [[metabolic]] disorders.
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.


==Pathophysiology==
==Pathophysiology==
===Parathyroid, Vitamin D, and mineral homeostasis===
===Parathyroid, Vitamin D, and Mineral Homeostasis===
The effect of [[parathyroid hormone]] on [[mineral]] [[metabolism]] is as follows:<ref name="pmid14184232">{{cite journal |vauthors=HARRISON MT |title=INTERRELATIONSHIPS OF VITAMIN D AND PARATHYROID HORMONE IN CALCIUM HOMEOSTASIS |journal=Postgrad Med J |volume=40 |issue= |pages=497–505 |year=1964 |pmid=14184232 |pmc=2482768 |doi= |url=}}</ref><ref>{{cite book | last = Nussey | first = Stephen | title = Endocrinology : an integrated approach | publisher = Bios NCBI | location = Oxford, UK Bethesda, Md | year = 2001 | isbn = 1-85996-252-1 }}</ref>
The effect of [[parathyroid hormone]] on [[mineral]] [[metabolism]] is as follows:<ref name="pmid14184232">{{cite journal |vauthors=HARRISON MT |title=INTERRELATIONSHIPS OF VITAMIN D AND PARATHYROID HORMONE IN CALCIUM HOMEOSTASIS |journal=Postgrad Med J |volume=40 |issue= |pages=497–505 |year=1964 |pmid=14184232 |pmc=2482768 |doi= |url=}}</ref><ref>{{cite book | last = Nussey | first = Stephen | title = Endocrinology : an integrated approach | publisher = Bios NCBI | location = Oxford, UK Bethesda, Md | year = 2001 | isbn = 1-85996-252-1 }}</ref>
*Effect of [[parathyroid hormone]] on [[inorganic phosphate]] [[metabolism]]:
*Effect of [[parathyroid hormone]] on [[inorganic phosphate]] [[metabolism]]:
**Increases [[excretion]] of [[Phosphate|inorganic phosphate]] from [[kidney]] resulting in decreased serum concentration of [[phosphate]].
**Increases [[excretion]] of [[Phosphate|inorganic phosphate]] from [[kidney]] resulting in decreased [[serum]] concentration of [[phosphate]].
*Effect on [[parathyroid hormone]] on [[calcium]] [[metabolism]]:
*Effect on [[parathyroid hormone]] on [[calcium]] [[metabolism]]:
**Direct effect:
**Direct effect:
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***Decreases [[excretion]] from [[kidney]].
***Decreases [[excretion]] from [[kidney]].
**Indirect effect:
**Indirect effect:
***Increases conversion of inactive [[25-hydroxy vitamin D]] to the active [[1,25-dihydroxy vitamin D]] which increases absorption of [[calcium]] from [[gut]]. Decreased phosphate concentration also increases this conversion process. [[Vitamin D]] shows synergism with [[parathyroid hormone]] action on [[bone]].
***Increases conversion of inactive [[25-hydroxy vitamin D]] to the active [[1,25-dihydroxy vitamin D]] which increases absorption of [[calcium]] from [[gut]]. Decreased [[phosphate]] concentration also increases this conversion process. [[Vitamin D]] shows synergism with [[parathyroid hormone]] action on [[bone]].
***Decreased serum [[inorganic phosphate]] concentration prevents [[Precipitation (chemistry)|precipitation]] of [[calcium phosphate]] in [[Bone (disambiguation)|bones]].
***Decreased serum [[inorganic phosphate]] concentration prevents [[Precipitation (chemistry)|precipitation]] of [[calcium phosphate]] in [[Bone (disambiguation)|bones]].
**Both these direct and indirect mechanism results in an increased serum [[calcium]] concentration.
**Both these direct and indirect mechanism results in an increased [[serum]] [[calcium]] concentration.
*Effect of [[parathyroid hormone]] on [[magnesium]] concentration:
*Effect of [[parathyroid hormone]] on [[magnesium]] concentration:
**Decreases [[excretion]] of [[magnesium]] resulting in increased serum [[magnesium]] concentretion.
**Decreases [[excretion]] of [[magnesium]] resulting in increased serum [[magnesium]] concentretion.
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*[[Magnesium]] provides [[negative feedback]] on [[parathyroid hormone]].
*[[Magnesium]] provides [[negative feedback]] on [[parathyroid hormone]].
*[[Vitamin D]] decreases the concentration of [[parathyroid hormone]].
*[[Vitamin D]] decreases the concentration of [[parathyroid hormone]].
The sequence of events is shown in the algorithm below:
<br><br><br>
 
<br>
 
<br>
 
<br>


<div style="text-align: center;">'''The Sequence of Events in Parathyroid, Vitamin D, and Mineral Homeostasis''' </div>
<br>
{{familytree/start |}}
{{familytree/start |}}
{{familytree | | | | | | | | | | | | A01 |A01='''Parathyroid hormone'''}}  
{{familytree | | | | | | | | | | | | A01 |A01='''Parathyroid hormone'''}}  
{{familytree | | | | | | | |,|-|-|-|-|^|-|-|-|-|-|-|-|-|-|-|-|-|-|-|.|}}
{{familytree | | | | | | | |,|-|-|-|-|^|-|-|-|-|-|-|-|-|-|-|-|-|-|-|.|}}
{{familytree | | | | | | | B01 | | | | | | | | | | | | | | | | | | B02 | | |B01=Kidney|B02=Bone}}
{{familytree | | | | | | | B01 | | | | | | | | | | | | | | | | | | B02 | | |B01=[[Kidney]]|B02=[[Bone]]}}
{{familytree | |,|-|-|-|-|-|+|-|-|-|-|v|-|-|-|-|-|-|.| | | | | | | |!| }}
{{familytree | |,|-|-|-|-|-|+|-|-|-|-|v|-|-|-|-|-|-|.| | | | | | | |!| }}
{{familytree | C01 | | | | C02 | | | C03 | | | | | C04 | | | | | | C05 |C01=Decreased excretion of magnesium|C02=Increasead conversion of inactive 25-hydroyxvitamin D to the active 1,25-dihydroyxvitamin D|C03=Increase excretion of inorganic phosphate|C04=Decrease excretion of calcium|C05=Increased resorption of bone}}
{{familytree | C01 | | | | C02 | | | C03 | | | | | C04 | | | | | | C05 |C01=Decreased [[excretion]] of [[magnesium]]|C02=Increasead conversion of inactive [[25-hydroyx vitamin D]] to the active [[1,25-dihydroy xvitamin D]]|C03=Increase [[excretion]] of inorganic [[phosphate]]|C04=Decrease [[excretion]] of [[calcium]]|C05=Increased [[resorption]] of [[bone]]}}
{{familytree | |!| | | | | |!| | | | |!| | | | | | |!| | | | | | | |!| |}}
{{familytree | |!| | | | | |!| | | | |!| | | | | | |!| | | | | | | |!| |}}
{{familytree | D01 | | | | D02 | | | D03 | | | | | |`|-|-|-|-|.| | |!|D01=Increased serum concentration of magnesium|D02=Increased absorption of calcium from gut|D03=Decreased serum concentration of inorganic phosphate}}
{{familytree | D01 | | | | D02 | | | D03 | | | | | |`|-|-|-|-|.| | |!|D01=Increased serum concentration of [[magnesium]]|D02=Increased absorption of [[calcium]] from [[gut]]|D03=Decreased [[serum]] concentration of inorganic [[phosphate]]}}
{{familytree | | | | | | | |!| | | | |!| | | | | | | | | | | |!| | |!|}}
{{familytree | | | | | | | |!| | | | |!| | | | | | | | | | | |!| | |!|}}
{{familytree | | | | | | | |!| | | | |`|-|-| E01 |-|-|-|-|.| |!| | |!| E01=Prevents precipitation of calcium phosphate in bones}}
{{familytree | | | | | | | |!| | | | |`|-|-| E01 |-|-|-|-|.| |!| | |!| E01=Prevents precipitation of [[calcium phosphate]] in [[bones]]}}
{{familytree | | | | | | | |!| | | | | | | | | | | | | | |!| |!| | |!| | | | | |}}  
{{familytree | | | | | | | |!| | | | | | | | | | | | | | |!| |!| | |!| | | | | |}}  
{{familytree | | | | | | | |`|-|-|-|-|-|-|-|-|-|-|-|-|-|-| F01 |-|-|'| | |F01=Increased serum concentration of calcium}}
{{familytree | | | | | | | |`|-|-|-|-|-|-|-|-|-|-|-|-|-|-| F01 |-|-|'| | |F01=Increased serum concentration of [[calcium]]}}
{{familytree/end}}
{{familytree/end}}


<br>


===Calcium-sensing receptors===
===Calcium-sensing receptors===
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] are present on [[Parathyroid gland|parathyroid glands]]. They are a type of 7-transmembrane receptors in [[G-protein coupled receptors]] superfamily of receptors.<ref name="pmid8255296">{{cite journal| author=Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O et al.| title=Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. | journal=Nature | year= 1993 | volume= 366 | issue= 6455 | pages= 575-80 | pmid=8255296 | doi=10.1038/366575a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8255296  }} </ref>
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] are present on [[Parathyroid gland|parathyroid glands]]. They are a type of 7-[[transmembrane receptors]] in [[G-protein coupled receptors]] superfamily of receptors.<ref name="pmid8255296">{{cite journal| author=Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O et al.| title=Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. | journal=Nature | year= 1993 | volume= 366 | issue= 6455 | pages= 575-80 | pmid=8255296 | doi=10.1038/366575a0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8255296  }} </ref>
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] sense change in [[extracellular]] concentration of ionized [[calcium]].<ref name="pmid7791841">{{cite journal| author=Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D et al.| title=Calcium-ion-sensing cell-surface receptors. | journal=N Engl J Med | year= 1995 | volume= 333 | issue= 4 | pages= 234-40 | pmid=7791841 | doi=10.1056/NEJM199507273330407 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7791841  }} </ref>
*[[Calcium]]-sensing [[Receptor (biochemistry)|receptors]] sense change in [[extracellular]] concentration of ionized [[calcium]].<ref name="pmid7791841">{{cite journal| author=Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D et al.| title=Calcium-ion-sensing cell-surface receptors. | journal=N Engl J Med | year= 1995 | volume= 333 | issue= 4 | pages= 234-40 | pmid=7791841 | doi=10.1056/NEJM199507273330407 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7791841  }} </ref>


<br>


===Pathogenesis===
===Pathogenesis===
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**[[Vitamin D]] mediated [[absorption]] of [[calcium]] from [[intestine]].
**[[Vitamin D]] mediated [[absorption]] of [[calcium]] from [[intestine]].
*This leads to [[hypocalcemia]].
*This leads to [[hypocalcemia]].
<br>
<br>
<br>


{{Family tree/start}}
{{Family tree/start}}
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{{Family tree| | C01 | | | C02 | | | | C03 | | | C04 | |C01=Decrease reabsorption of calcium from bone|C02=Decrease excretion of phosphate|C03=Decrease reabsorbtion of calcium from distal tubules|C04=Decrease vitamin D mediated absorption of calcium from intestine}}
{{Family tree| | C01 | | | C02 | | | | C03 | | | C04 | |C01=Decrease reabsorption of calcium from bone|C02=Decrease excretion of phosphate|C03=Decrease reabsorbtion of calcium from distal tubules|C04=Decrease vitamin D mediated absorption of calcium from intestine}}
{{Family tree/end}}
{{Family tree/end}}
<br>


===Post-surgical Hypoparathyroidism===
===Post-surgical Hypoparathyroidism===
*[[Anterior neck surgery]] most commonly causes hypoparathyroidism. Majority of time this hypoparathyroidism is transient i.e. it resolves within 6 months.<ref name="pmid21812031">{{cite journal |vauthors=Bilezikian JP, Khan A, Potts JT, Brandi ML, Clarke BL, Shoback D, Jüppner H, D'Amour P, Fox J, Rejnmark L, Mosekilde L, Rubin MR, Dempster D, Gafni R, Collins MT, Sliney J, Sanders J |title=Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research |journal=J. Bone Miner. Res. |volume=26 |issue=10 |pages=2317–37 |year=2011 |pmid=21812031 |pmc=3405491 |doi=10.1002/jbmr.483 |url=}}</ref><ref name="pmid25982044">{{cite journal |vauthors=Ritter K, Elfenbein D, Schneider DF, Chen H, Sippel RS |title=Hypoparathyroidism after total thyroidectomy: incidence and resolution |journal=J. Surg. Res. |volume=197 |issue=2 |pages=348–53 |year=2015 |pmid=25982044 |pmc=4466142 |doi=10.1016/j.jss.2015.04.059 |url=}}</ref><ref name="pmid12678507">{{cite journal |vauthors=Sturniolo G, Lo Schiavo MG, Tonante A, D'Alia C, Bonanno L |title=Hypocalcemia and hypoparathyroidism after total thyroidectomy: a clinical biological study and surgical considerations |journal=Int. J. Surg. Investig. |volume=2 |issue=2 |pages=99–105 |year=2000 |pmid=12678507 |doi= |url=}}</ref>
*Anterior [[neck surgery]] most commonly causes hypoparathyroidism. Majority of time this hypoparathyroidism is transient i.e. it resolves within 6 months.<ref name="pmid21812031">{{cite journal |vauthors=Bilezikian JP, Khan A, Potts JT, Brandi ML, Clarke BL, Shoback D, Jüppner H, D'Amour P, Fox J, Rejnmark L, Mosekilde L, Rubin MR, Dempster D, Gafni R, Collins MT, Sliney J, Sanders J |title=Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research |journal=J. Bone Miner. Res. |volume=26 |issue=10 |pages=2317–37 |year=2011 |pmid=21812031 |pmc=3405491 |doi=10.1002/jbmr.483 |url=}}</ref><ref name="pmid25982044">{{cite journal |vauthors=Ritter K, Elfenbein D, Schneider DF, Chen H, Sippel RS |title=Hypoparathyroidism after total thyroidectomy: incidence and resolution |journal=J. Surg. Res. |volume=197 |issue=2 |pages=348–53 |year=2015 |pmid=25982044 |pmc=4466142 |doi=10.1016/j.jss.2015.04.059 |url=}}</ref><ref name="pmid12678507">{{cite journal |vauthors=Sturniolo G, Lo Schiavo MG, Tonante A, D'Alia C, Bonanno L |title=Hypocalcemia and hypoparathyroidism after total thyroidectomy: a clinical biological study and surgical considerations |journal=Int. J. Surg. Investig. |volume=2 |issue=2 |pages=99–105 |year=2000 |pmid=12678507 |doi= |url=}}</ref>
The features of hypoparathyroidism should persist for atleast 6 month after surgery to be diagnosed as chronic hypoparathyroidism.
*The features of hypoparathyroidism should persist for atleast 6 month after surgery to be diagnosed as chronic hypoparathyroidism.
* 30–60% Patients undergoing total [[thyroidectomy]] develops [[hypocalcaemia]] within 24 hours as an initial manifestation of postoperative parathyroid failure. About 60%-70% of these cases resolve within 4–6 weeks after surgery. Remaining cases progress to develop protracted hypoparathyroidism requiring continuous treatment. Around 15–25% of patients with protracted hypoparathyroidism progress to chronic hypoparathyroidism.<ref name="pmid26160136">{{cite journal |vauthors=Bollerslev J, Rejnmark L, Marcocci C, Shoback DM, Sitges-Serra A, van Biesen W, Dekkers OM |title=European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults |journal=Eur. J. Endocrinol. |volume=173 |issue=2 |pages=G1–20 |year=2015 |pmid=26160136 |doi=10.1530/EJE-15-0628 |url=}}</ref>
* 30–60% Patients undergoing total [[thyroidectomy]] develops [[hypocalcaemia]] within 24 hours as an initial manifestation of postoperative [[Parathyroid gland|parathyroid]] failure. About 60%-70% of these cases resolve within 4–6 weeks after [[surgery]]. Remaining cases progress to develop protracted hypoparathyroidism requiring continuous treatment. Around 15–25% of patients with protracted hypoparathyroidism progress to chronic hypoparathyroidism.<ref name="pmid26160136">{{cite journal |vauthors=Bollerslev J, Rejnmark L, Marcocci C, Shoback DM, Sitges-Serra A, van Biesen W, Dekkers OM |title=European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults |journal=Eur. J. Endocrinol. |volume=173 |issue=2 |pages=G1–20 |year=2015 |pmid=26160136 |doi=10.1530/EJE-15-0628 |url=}}</ref>
*Factors favorring recovery from protracted hypoparathyroidism include:
*Factors favorring recovery from protracted hypoparathyroidism include:
**Number of [[parathyroid glands]] remaining in situ.
**Number of [[parathyroid glands]] remaining in situ.
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| style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Autoimmune polyendocrine syndrome type 1]]'''<ref name="pmid2348835">{{cite journal |vauthors=Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J |title=Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients |journal=N. Engl. J. Med. |volume=322 |issue=26 |pages=1829–36 |year=1990 |pmid=2348835 |doi=10.1056/NEJM199006283222601 |url=}}</ref>
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Autoimmune polyendocrine syndrome type 1]]'''<ref name="pmid2348835">{{cite journal |vauthors=Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J |title=Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients |journal=N. Engl. J. Med. |volume=322 |issue=26 |pages=1829–36 |year=1990 |pmid=2348835 |doi=10.1056/NEJM199006283222601 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Mutation in AIRE gene
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Mutation in AIRE [[gene]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Also known as [[Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome|autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy]] ([[APECED syndrome|APECED]]).
*Also known as [[Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome|autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy]] ([[APECED syndrome|APECED]])
*Presents with a variable combination of:
*Presents with a variable combination of:
**Failure of the [[Parathyroid gland|parathyroid glands]], [[adrenal cortex]], [[gonads]], [[pancreatic beta cells]], [[gastric parietal cells]], [[thyroid gland]], and [[hepatitis]].
**Failure of the [[Parathyroid gland|parathyroid glands]], [[adrenal cortex]], [[gonads]], [[pancreatic beta cells]], [[gastric parietal cells]], [[thyroid gland]], and [[hepatitis]]
**Chronic [[mucocutaneous]] [[candidiasis]]
**Chronic [[mucocutaneous]] [[candidiasis]]
**[[Dystrophy]] of [[dental enamel]] and [[nails]], [[alopecia]], [[vitiligo]], and keratopathy.
**[[Dystrophy]] of [[dental enamel]] and [[nails]], [[alopecia]], [[vitiligo]], and keratopathy
|-
|-
| colspan="2" rowspan="7" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Isolated'''
| colspan="2" rowspan="7" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Isolated'''
| colspan="2" rowspan="5" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Familial Isolated hypoparathyroidism'''
| colspan="2" rowspan="5" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Familial Isolated hypoparathyroidism'''
| rowspan="2" style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| rowspan="2" style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |PTH gene<ref name="pmid2212001">{{cite journal |vauthors=Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM |title=Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism |journal=J. Clin. Invest. |volume=86 |issue=4 |pages=1084–7 |year=1990 |pmid=2212001 |pmc=296835 |doi=10.1172/JCI114811 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |PTH [[gene]]<ref name="pmid2212001">{{cite journal |vauthors=Arnold A, Horst SA, Gardella TJ, Baba H, Levine MA, Kronenberg HM |title=Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism |journal=J. Clin. Invest. |volume=86 |issue=4 |pages=1084–7 |year=1990 |pmid=2212001 |pmc=296835 |doi=10.1172/JCI114811 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of hypocalcemia including:
*Clinical features of hypocalcemia including:
**[[Tetany]] (hallmark of acute [[hypocalcemia]]).
**[[Tetany]] (hallmark of acute [[hypocalcemia]])
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area.
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area
**[[Carpopedal spasm|Carpopedal spasms]].
**[[Carpopedal spasm|Carpopedal spasms]]
**Circumoral [[numbness]].
**Circumoral [[numbness]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Glial cells missing [[GCM2]] gene<ref name="pmid18712808">{{cite journal |vauthors=Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN |title=Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism |journal=Hum. Mutat. |volume=30 |issue=1 |pages=85–92 |year=2009 |pmid=18712808 |doi=10.1002/humu.20827 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Glial cells]] missing [[GCM2]] [[gene]]<ref name="pmid18712808">{{cite journal |vauthors=Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN |title=Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism |journal=Hum. Mutat. |volume=30 |issue=1 |pages=85–92 |year=2009 |pmid=18712808 |doi=10.1002/humu.20827 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of hypocalcemia including:
*Clinical features of [[hypocalcemia]] including:
**[[Tetany]] (hallmark of acute [[hypocalcemia]]).
**[[Tetany]] (hallmark of acute [[hypocalcemia]])
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area.
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area
**[[Carpopedal spasm|Carpopedal spasms]].
**[[Carpopedal spasm|Carpopedal spasms]]
**Circumoral [[numbness]].
**Circumoral [[numbness]]
*[[Dominant negative mutation]].
*[[Dominant negative mutation]]
|-
|-
| rowspan="2" style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| rowspan="2" style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |PTH gene<ref name="pmid10523031">{{cite journal |vauthors=Sunthornthepvarakul T, Churesigaew S, Ngowngarmratana S |title=A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism |journal=J. Clin. Endocrinol. Metab. |volume=84 |issue=10 |pages=3792–6 |year=1999 |pmid=10523031 |doi=10.1210/jcem.84.10.6070 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Parathyroid hormone|PTH]] [[gene]]<ref name="pmid10523031">{{cite journal |vauthors=Sunthornthepvarakul T, Churesigaew S, Ngowngarmratana S |title=A novel mutation of the signal peptide of the preproparathyroid hormone gene associated with autosomal recessive familial isolated hypoparathyroidism |journal=J. Clin. Endocrinol. Metab. |volume=84 |issue=10 |pages=3792–6 |year=1999 |pmid=10523031 |doi=10.1210/jcem.84.10.6070 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of hypocalcemia including:
*Clinical features of [[hypocalcemia]] including:
**[[Tetany]] (hallmark of acute [[hypocalcemia]]).
**[[Tetany]] (hallmark of acute [[hypocalcemia]])
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area.
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area
**[[Carpopedal spasm|Carpopedal spasms]].
**[[Carpopedal spasm|Carpopedal spasms]]
**Circumoral [[numbness]].
**Circumoral [[numbness]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Glial cells missing 2 ([[GCM2]]) gene<ref name="pmid18712808">{{cite journal |vauthors=Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN |title=Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism |journal=Hum. Mutat. |volume=30 |issue=1 |pages=85–92 |year=2009 |pmid=18712808 |doi=10.1002/humu.20827 |url=}}</ref><ref name="pmid11602629">{{cite journal |vauthors=Ding C, Buckingham B, Levine MA |title=Familial isolated hypoparathyroidism caused by a mutation in the gene for the transcription factor GCMB |journal=J. Clin. Invest. |volume=108 |issue=8 |pages=1215–20 |year=2001 |pmid=11602629 |pmc=209530 |doi=10.1172/JCI13180 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Glial cells]] missing 2 ([[GCM2]]) [[gene]]<ref name="pmid18712808">{{cite journal |vauthors=Canaff L, Zhou X, Mosesova I, Cole DE, Hendy GN |title=Glial cells missing-2 (GCM2) transactivates the calcium-sensing receptor gene: effect of a dominant-negative GCM2 mutant associated with autosomal dominant hypoparathyroidism |journal=Hum. Mutat. |volume=30 |issue=1 |pages=85–92 |year=2009 |pmid=18712808 |doi=10.1002/humu.20827 |url=}}</ref><ref name="pmid11602629">{{cite journal |vauthors=Ding C, Buckingham B, Levine MA |title=Familial isolated hypoparathyroidism caused by a mutation in the gene for the transcription factor GCMB |journal=J. Clin. Invest. |volume=108 |issue=8 |pages=1215–20 |year=2001 |pmid=11602629 |pmc=209530 |doi=10.1172/JCI13180 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of hypocalcemia including:
*Clinical features of hypocalcemia including:
**[[Tetany]] (hallmark of acute [[hypocalcemia]]).
**[[Tetany]] (hallmark of acute [[hypocalcemia]])
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area.
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area
**[[Carpopedal spasm|Carpopedal spasms]].
**[[Carpopedal spasm|Carpopedal spasms]]
**Circumoral [[numbness]].
**Circumoral [[numbness]]
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[X-linked]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[X-linked]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[FHL1 (gene)|FHL1]] gene (exon 4, c.C283T, p.R95W) on chromosome locus Xq26-q27<ref name="pmid28444561">{{cite journal |vauthors=Pillar N, Pleniceanu O, Fang M, Ziv L, Lahav E, Botchan S, Cheng L, Dekel B, Shomron N |title=A rare variant in the FHL1 gene associated with X-linked recessive hypoparathyroidism |journal=Hum. Genet. |volume=136 |issue=7 |pages=835–845 |year=2017 |pmid=28444561 |pmc=5487855 |doi=10.1007/s00439-017-1804-9 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[FHL1 (gene)|FHL1]] [[gene]] ([[exon]] 4, c.C283T, p.R95W) on [[chromosome]] [[locus]] Xq26-q27<ref name="pmid28444561">{{cite journal |vauthors=Pillar N, Pleniceanu O, Fang M, Ziv L, Lahav E, Botchan S, Cheng L, Dekel B, Shomron N |title=A rare variant in the FHL1 gene associated with X-linked recessive hypoparathyroidism |journal=Hum. Genet. |volume=136 |issue=7 |pages=835–845 |year=2017 |pmid=28444561 |pmc=5487855 |doi=10.1007/s00439-017-1804-9 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of hypocalcemia including:
*Clinical features of hypocalcemia including:
**[[Tetany]] (hallmark of acute [[hypocalcemia]]).
**[[Tetany]] (hallmark of acute [[hypocalcemia]])
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area.
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area
**[[Carpopedal spasm|Carpopedal spasms]].
**[[Carpopedal spasm|Carpopedal spasms]]
**Circumoral [[numbness]].
**Circumoral [[numbness]]
|-
|-
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Autosomal dominant hypercalcemia'''<ref name="pmid278036722">{{cite journal |vauthors=Roszko KL, Bi RD, Mannstadt M |title=Autosomal Dominant Hypocalcemia (Hypoparathyroidism) Types 1 and 2 |journal=Front Physiol |volume=7 |issue= |pages=458 |year=2016 |pmid=27803672 |pmc=5067375 |doi=10.3389/fphys.2016.00458 |url=}}</ref>
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Autosomal dominant hypercalcemia]]'''<ref name="pmid278036722">{{cite journal |vauthors=Roszko KL, Bi RD, Mannstadt M |title=Autosomal Dominant Hypocalcemia (Hypoparathyroidism) Types 1 and 2 |journal=Front Physiol |volume=7 |issue= |pages=458 |year=2016 |pmid=27803672 |pmc=5067375 |doi=10.3389/fphys.2016.00458 |url=}}</ref>
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Autosomal dominant hypocalcemia type 1'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Autosomal dominant]] hypocalcemia type 1'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Calcium-sensing receptor]] [[gene mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Calcium-sensing receptor]] [[gene mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Calcium-sensing receptor]] gene activating mutation.
*[[Calcium-sensing receptor]] gene activating [[mutation]]
*'''Most common genetic form''' of hypoparathyroidism.
*'''Most common [[genetic]] form''' of hypoparathyroidism
*Also known as familial hypercalciuric hypocalcemia.
*Also known as familial hypercalciuric hypocalcemia
*The activating mutation results in gain in function.
*The activating [[mutation]] results in gain in function
*[[Calcium-sensing receptor]] gene activating mutation can also cause mild [[Bartter syndrome]] type 5. This mutation cause the inhibition of apical potassium channel in the thick ascending limb of the [[loop of Henle]] in the [[kidney]].<ref name="pmid17048213">{{cite journal |vauthors=Vezzoli G, Arcidiacono T, Paloschi V, Terranegra A, Biasion R, Weber G, Mora S, Syren ML, Coviello D, Cusi D, Bianchi G, Soldati L |title=Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome |journal=J. Nephrol. |volume=19 |issue=4 |pages=525–8 |year=2006 |pmid=17048213 |doi= |url=}}</ref><ref name="pmid25932037">{{cite journal |vauthors=Choi KH, Shin CH, Yang SW, Cheong HI |title=Autosomal dominant hypocalcemia with Bartter syndrome due to a novel activating mutation of calcium sensing receptor, Y829C |journal=Korean J Pediatr |volume=58 |issue=4 |pages=148–53 |year=2015 |pmid=25932037 |pmc=4414630 |doi=10.3345/kjp.2015.58.4.148 |url=}}</ref>
:'''NOTE:''' [[Calcium-sensing receptor]] [[gene]] activating [[mutation]] can also cause mild [[Bartter syndrome]] type 5. This [[mutation]] cause the inhibition of apical [[potassium]] channel in the [[Thick ascending limb of loop of Henle|thick ascending limb]] of the [[loop of Henle]] in the [[kidney]].<ref name="pmid17048213">{{cite journal |vauthors=Vezzoli G, Arcidiacono T, Paloschi V, Terranegra A, Biasion R, Weber G, Mora S, Syren ML, Coviello D, Cusi D, Bianchi G, Soldati L |title=Autosomal dominant hypocalcemia with mild type 5 Bartter syndrome |journal=J. Nephrol. |volume=19 |issue=4 |pages=525–8 |year=2006 |pmid=17048213 |doi= |url=}}</ref><ref name="pmid25932037">{{cite journal |vauthors=Choi KH, Shin CH, Yang SW, Cheong HI |title=Autosomal dominant hypocalcemia with Bartter syndrome due to a novel activating mutation of calcium sensing receptor, Y829C |journal=Korean J Pediatr |volume=58 |issue=4 |pages=148–53 |year=2015 |pmid=25932037 |pmc=4414630 |doi=10.3345/kjp.2015.58.4.148 |url=}}</ref>
|-
|-
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Autosomal dominant hypocalcemia type 2'''
| style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Autosomal dominant]] hypocalcemia type 2'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |G protein G11 ([[GNA11]]) mutation
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[G protein]] G11 ([[GNA11]]) [[mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of hypocalcemia including:
*Clinical features of [[hypocalcemia]] including:
**[[Tetany]] (hallmark of acute [[hypocalcemia]]).
**[[Tetany]] (hallmark of acute [[hypocalcemia]])
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area.
**[[Paresthesia]] in [[fingertips]], [[toes]], and perioral area
**[[Carpopedal spasm|Carpopedal spasms]].
**[[Carpopedal spasm|Carpopedal spasms]]
**Circumoral [[numbness]].
**Circumoral [[numbness]]
|-
|-
| colspan="2" rowspan="6" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Congenital multisystem syndromes'''
| colspan="2" rowspan="6" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Congenital multisystem syndromes'''
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[DiGeorge syndrome]]'''<ref name="pmid21049214">{{cite journal |vauthors=Fomin AB, Pastorino AC, Kim CA, Pereira CA, Carneiro-Sampaio M, Abe-Jacob CM |title=DiGeorge Syndrome: a not so rare disease |journal=Clinics (Sao Paulo) |volume=65 |issue=9 |pages=865–9 |year=2010 |pmid=21049214 |pmc=2954737 |doi= |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[DiGeorge syndrome]]'''<ref name="pmid21049214">{{cite journal |vauthors=Fomin AB, Pastorino AC, Kim CA, Pereira CA, Carneiro-Sampaio M, Abe-Jacob CM |title=DiGeorge Syndrome: a not so rare disease |journal=Clinics (Sao Paulo) |volume=65 |issue=9 |pages=865–9 |year=2010 |pmid=21049214 |pmc=2954737 |doi= |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[22q11.2 deletion syndrome|22q11.2 deletion]].
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[22q11.2 deletion syndrome|22q11.2 deletion]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Presents with [[thymus]] [[dysfunction]], [[cardiac]] defects, [[immunodeficiency]], [[hypocalcemia]], and other clinical problems.
* Presents with:
*Also known as [[22q11.2DS]], [[CATCH 22 syndrome]], [[Cayler cardiofacial syndrome]], [[conotruncal anomaly face syndrome]] ([[CTAF]]), [[deletion 22q11.2 syndrome]], [[Sedlackova syndrome]], [[Shprintzen syndrome]], VCFS, [[velocardiofacial syndrome]], and velo-cardio-facial syndrome.
**[[Thymus]] [[dysfunction]]
*[[CATCH 22 syndrome|CATCH 22]] stands for [[cardiac]] defects, abnormal facies, [[thymic]] [[aplasia]], [[cleft palate]], and [[hypocalcemia]] with [[22q11.2 deletion syndrome|22q11.2 deletion]].
**[[Cardiac]] defects
**[[Immunodeficiency]]
**[[Hypocalcemia]]
**Other clinical problems
*Also known as:
**[[22q11.2DS]] or [[deletion 22q11.2 syndrome]]
**[[CATCH 22 syndrome]]
**[[Cayler cardiofacial syndrome]]
**[[Conotruncal anomaly face syndrome]] ([[CTAF]])
**[[Sedlackova syndrome]]
**[[Shprintzen syndrome]]
**[[Velocardiofacial syndrome|VCFS]] or [[velocardiofacial syndrome]] or [[Velocardiofacial syndrome|velo-cardio-facial syndrome]]
*[[CATCH 22 syndrome|CATCH 22]] stands for:
**[[Cardiac]] defects
**Abnormal facies
**[[Thymic]] [[aplasia]]
**[[Cleft palate]]
**[[Hypocalcemia]] with [[22q11.2 deletion syndrome|22q11.2 deletion]]
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[CHARGE syndrome]]'''<ref name="pmid21995344">{{cite journal |vauthors=Jain S, Kim HG, Lacbawan F, Meliciani I, Wenzel W, Kurth I, Sharma J, Schoeneman M, Ten S, Layman LC, Jacobson-Dickman E |title=Unique phenotype in a patient with CHARGE syndrome |journal=Int J Pediatr Endocrinol |volume=2011 |issue= |pages=11 |year=2011 |pmid=21995344 |pmc=3216247 |doi=10.1186/1687-9856-2011-11 |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[CHARGE syndrome]]'''<ref name="pmid21995344">{{cite journal |vauthors=Jain S, Kim HG, Lacbawan F, Meliciani I, Wenzel W, Kurth I, Sharma J, Schoeneman M, Ten S, Layman LC, Jacobson-Dickman E |title=Unique phenotype in a patient with CHARGE syndrome |journal=Int J Pediatr Endocrinol |volume=2011 |issue= |pages=11 |year=2011 |pmid=21995344 |pmc=3216247 |doi=10.1186/1687-9856-2011-11 |url=}}</ref>
Line 200: Line 209:
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |CHD7 G744S [[missense mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |CHD7 G744S [[missense mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Presents with [[coloboma]], [[heart]] defects, [[Choanal atresia|atresia choanae]], retarded growth and development, [[Genitourinary pathology|genitourinary abnormalities]], and [[ear]] anomalies and/or [[deafness]].
* Presents with:
**[[Coloboma]]
**[[Cardiac]] defects
**[[Choanal atresia|Atresia choanae]]
**Retarded growth and development
**[[Genitourinary pathology|Genitourinary abnormalities]]
**[[Ear]] anomalies and/or [[deafness]]
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Kenny-Caffey syndrome type 1'''<ref name="pmid23087875">{{cite journal |vauthors=Metwalley KA, Farghaly HS |title=Kenny-Caffey syndrome type 1 in an Egyptian girl |journal=Indian J Endocrinol Metab |volume=16 |issue=5 |pages=827–9 |year=2012 |pmid=23087875 |pmc=3475915 |doi=10.4103/2230-8210.100645 |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Kenny-Caffey syndrome type 1]]'''<ref name="pmid23087875">{{cite journal |vauthors=Metwalley KA, Farghaly HS |title=Kenny-Caffey syndrome type 1 in an Egyptian girl |journal=Indian J Endocrinol Metab |volume=16 |issue=5 |pages=827–9 |year=2012 |pmid=23087875 |pmc=3475915 |doi=10.4103/2230-8210.100645 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Deletion of the [[TBCE]] gene
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Deletion of the [[TBCE]] [[gene]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Presents with [[hypoparathyroidism]] due to absent [[Parathyroid gland|parathyroid tissue]], growth retardation, medullary stenosis of tubular bones.
* Presents with [[hypoparathyroidism]] due to:
**Absent [[Parathyroid gland|parathyroid tissue]]
**Growth retardation
**[[Medullary]] stenosis of tubular [[bones]]
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Kenny-Caffey syndrome type 2'''<ref name="pmid23996431">{{cite journal |vauthors=Isojima T, Doi K, Mitsui J, Oda Y, Tokuhiro E, Yasoda A, Yorifuji T, Horikawa R, Yoshimura J, Ishiura H, Morishita S, Tsuji S, Kitanaka S |title=A recurrent de novo FAM111A mutation causes Kenny-Caffey syndrome type 2 |journal=J. Bone Miner. Res. |volume=29 |issue=4 |pages=992–8 |year=2014 |pmid=23996431 |doi=10.1002/jbmr.2091 |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Kenny-Caffey syndrome type 2]]'''<ref name="pmid23996431">{{cite journal |vauthors=Isojima T, Doi K, Mitsui J, Oda Y, Tokuhiro E, Yasoda A, Yorifuji T, Horikawa R, Yoshimura J, Ishiura H, Morishita S, Tsuji S, Kitanaka S |title=A recurrent de novo FAM111A mutation causes Kenny-Caffey syndrome type 2 |journal=J. Bone Miner. Res. |volume=29 |issue=4 |pages=992–8 |year=2014 |pmid=23996431 |doi=10.1002/jbmr.2091 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal dominant]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Mutation of “family with sequence similarity 111, member A″ (FAM111A) gene located on chromosome locus 11q12.1
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Mutation of “family with sequence similarity 111, member A″ (FAM111A) [[gene]] located on [[chromosome]] [[locus]] 11q12.1
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Patients with Kenny-Caffey sundrome type 2 have same clinical features as Kenny-Caffey syndrome type 1 except for [[mental retardation]].
*Similar clinical features as Kenny-Caffey syndrome type 1
*Except for [[mental retardation]]
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Sanjad-Sakati syndrome'''<ref name="pmid22043344">{{cite journal |vauthors=Rafique B, Al-Yaarubi S |title=Sanjad-Sakati Syndrome in Omani children |journal=Oman Med J |volume=25 |issue=3 |pages=227–9 |year=2010 |pmid=22043344 |pmc=3191633 |doi=10.5001/omj.2010.63 |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Sanjad-Sakati syndrome]]'''<ref name="pmid22043344">{{cite journal |vauthors=Rafique B, Al-Yaarubi S |title=Sanjad-Sakati Syndrome in Omani children |journal=Oman Med J |volume=25 |issue=3 |pages=227–9 |year=2010 |pmid=22043344 |pmc=3191633 |doi=10.5001/omj.2010.63 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |Mutation in [[TBCE]] gene.
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Mutation]] in [[TBCE]] [[gene]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
* Sanjad-Sakati syndrome in exclusively found in arabian descent population.
*Exclusively found in arabian descent population
* Presents with hypoparathyroidism, [[intellectual disability]], [[Dysmorphic feature|dysmorphism]].
* Presents with:
**Hypoparathyroidism
**[[Intellectual disability]]
**[[Dysmorphic feature|Dysmorphism]]
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Barakat syndrome]]'''<ref name="pmid11389161">{{cite journal |vauthors=Muroya K, Hasegawa T, Ito Y, Nagai T, Isotani H, Iwata Y, Yamamoto K, Fujimoto S, Seishu S, Fukushima Y, Hasegawa Y, Ogata T |title=GATA3 abnormalities and the phenotypic spectrum of HDR syndrome |journal=J. Med. Genet. |volume=38 |issue=6 |pages=374–80 |year=2001 |pmid=11389161 |pmc=1734904 |doi= |url=}}</ref><ref name="pmid10935639">{{cite journal |vauthors=Van Esch H, Groenen P, Nesbit MA, Schuffenhauer S, Lichtner P, Vanderlinden G, Harding B, Beetz R, Bilous RW, Holdaway I, Shaw NJ, Fryns JP, Van de Ven W, Thakker RV, Devriendt K |title=GATA3 haplo-insufficiency causes human HDR syndrome |journal=Nature |volume=406 |issue=6794 |pages=419–22 |year=2000 |pmid=10935639 |doi=10.1038/35019088 |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Barakat syndrome]]'''<ref name="pmid11389161">{{cite journal |vauthors=Muroya K, Hasegawa T, Ito Y, Nagai T, Isotani H, Iwata Y, Yamamoto K, Fujimoto S, Seishu S, Fukushima Y, Hasegawa Y, Ogata T |title=GATA3 abnormalities and the phenotypic spectrum of HDR syndrome |journal=J. Med. Genet. |volume=38 |issue=6 |pages=374–80 |year=2001 |pmid=11389161 |pmc=1734904 |doi= |url=}}</ref><ref name="pmid10935639">{{cite journal |vauthors=Van Esch H, Groenen P, Nesbit MA, Schuffenhauer S, Lichtner P, Vanderlinden G, Harding B, Beetz R, Bilous RW, Holdaway I, Shaw NJ, Fryns JP, Van de Ven W, Thakker RV, Devriendt K |title=GATA3 haplo-insufficiency causes human HDR syndrome |journal=Nature |volume=406 |issue=6794 |pages=419–22 |year=2000 |pmid=10935639 |doi=10.1038/35019088 |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Mutation|Mutations]] in the [[GATA3]] gene
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Mutation|Mutations]] in the [[GATA3]] [[gene]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Also known as hypoparathyroidism, [[deafness]], and renal dysplasia (HDR) syndrome.
*Also known as hypoparathyroidism, [[deafness]], and [[renal]] [[dysplasia]] (HDR) syndrome.
*Presents with primary hypoparathyroidism, nerve [[deafness]], steroid-resistant [[nephrosis]].
*Presents with:
**Primary hypoparathyroidism
**Nerve [[deafness]]
**[[Steroid]]-resistant [[nephrosis]]
|-
|-
| rowspan="6" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Metabolic diseases'''
| rowspan="6" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Metabolic diseases'''
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Mitochondiral polyneuropathies'''<ref name="pmid27716753">{{cite journal |vauthors=Chow J, Rahman J, Achermann JC, Dattani MT, Rahman S |title=Mitochondrial disease and endocrine dysfunction |journal=Nat Rev Endocrinol |volume=13 |issue=2 |pages=92–104 |year=2017 |pmid=27716753 |doi=10.1038/nrendo.2016.151 |url=}}</ref>
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Mitochondiral polyneuropathies'''<ref name="pmid27716753">{{cite journal |vauthors=Chow J, Rahman J, Achermann JC, Dattani MT, Rahman S |title=Mitochondrial disease and endocrine dysfunction |journal=Nat Rev Endocrinol |volume=13 |issue=2 |pages=92–104 |year=2017 |pmid=27716753 |doi=10.1038/nrendo.2016.151 |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Kearns–Sayre syndrome'''
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Kearns–Sayre syndrome]]'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Mitochondrial inheritence
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[Mitochondrial]] inheritence
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | mtDNA deletion
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | mtDNA deletion
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Progressive external [[ophthalmoplegia]]
*Presents with:
*[[Retinitis pigmentosa]]
**Progressive external [[ophthalmoplegia]]
*[[Cardiomyopathy]]
**[[Retinitis pigmentosa]]
*[[Heart block]]
**[[Cardiomyopathy]]
**[[Heart block]]
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Maternally inherited diabetes and deafness (MIDD)'''
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Maternally inherited diabetes and deafness (MIDD)]]'''
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | Mitochondrial inheritence
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[Mitochondrial]] inheritence
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | MT‑TL1 defect
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | MT‑TL1 defect
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*[[Diabetes mellitus]]
*Presents with:
*[[Deafness]]
**[[Diabetes mellitus]]
**[[Deafness]]
|-
|-
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Mitochondrial enzyme deficiencies'''
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Mitochondrial enzyme deficiencies'''
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Mitochondrial trifunctional protein deficiency (MTP deficiency)'''<ref name="pmid16523289">{{cite journal |vauthors=Labarthe F, Benoist JF, Brivet M, Vianey-Saban C, Despert F, de Baulny HO |title=Partial hypoparathyroidism associated with mitochondrial trifunctional protein deficiency |journal=Eur. J. Pediatr. |volume=165 |issue=6 |pages=389–91 |year=2006 |pmid=16523289 |doi=10.1007/s00431-005-0052-5 |url=}}</ref><ref name="urlmitochondrial trifunctional protein deficiency - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency |title=mitochondrial trifunctional protein deficiency - Genetics Home Reference |format= |work= |accessdate=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Mitochondrial trifunctional protein deficiency]] ([[MTP deficiency]])'''<ref name="pmid16523289">{{cite journal |vauthors=Labarthe F, Benoist JF, Brivet M, Vianey-Saban C, Despert F, de Baulny HO |title=Partial hypoparathyroidism associated with mitochondrial trifunctional protein deficiency |journal=Eur. J. Pediatr. |volume=165 |issue=6 |pages=389–91 |year=2006 |pmid=16523289 |doi=10.1007/s00431-005-0052-5 |url=}}</ref><ref name="urlmitochondrial trifunctional protein deficiency - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/mitochondrial-trifunctional-protein-deficiency |title=mitochondrial trifunctional protein deficiency - Genetics Home Reference |format= |work= |accessdate=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | HADHA or HADHB gene mutation
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[HADHA]] or [[HADHB]] [[gene]] [[mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of mitochondrial trifunctional protein deficiency occurring '''during''' [[Infancy|'''infancy''']] include:
*Clinical features of [[mitochondrial trifunctional protein deficiency]] occurring:
**[[Feeding difficulties]]
** During [[Infancy|infancy]] include:
**[[Lethargy]]
***[[Feeding difficulties]]
**[[Hypoglycemia]]
***[[Lethargy]]
**[[Hypotonia]]
***[[Hypoglycemia]]
**[[Liver disease|Liver problems]]
***[[Hypotonia]]
*[[Infant|Infants]] with mitochondrial trifunctional protein deficiency are also at '''increased risk''' for:  
***[[Liver disease|Liver problems]]
**After [[infancy]] include:
***[[Hypotonia]]
***[[Muscle pain]]
***Breakdown of [[muscle]] [[Tissue (biology)|tissue]]
***[[Peripheral neuropathy]]
*[[Infant|Infants]] with [[mitochondrial trifunctional protein deficiency]] are also at increased risk for:  
**Serious [[heart]] problems
**Serious [[heart]] problems
**[[Breathing difficulties]]
**[[Breathing difficulties]]
**[[Coma]]
**[[Coma]]
**[[Sudden death]]
**[[Sudden death]]
*Clinical features of mitochondrial trifunctional protein deficiency occurring '''after [[infancy]]''' include:
 
**[[Hypotonia]]
**[[Muscle pain]]
**Breakdown of muscle tissue
**[[Peripheral neuropathy]]
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency]] ([[LCHAD deficiency]])'''<ref name="pmid9403664">{{cite journal |vauthors=Tyni T, Rapola J, Palotie A, Pihko H |title=Hypoparathyroidism in a patient with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency caused by the G1528C mutation |journal=J. Pediatr. |volume=131 |issue=5 |pages=766–8 |year=1997 |pmid=9403664 |doi= |url=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency]] ([[LCHAD deficiency]])'''<ref name="pmid9403664">{{cite journal |vauthors=Tyni T, Rapola J, Palotie A, Pihko H |title=Hypoparathyroidism in a patient with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency caused by the G1528C mutation |journal=J. Pediatr. |volume=131 |issue=5 |pages=766–8 |year=1997 |pmid=9403664 |doi= |url=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |G1528C gene mutation
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |G1528C [[gene]] [[mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of [[LCHAD deficiency]] include:
*Clinical features of [[LCHAD deficiency]] include:
Line 280: Line 309:
|-
|-
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Heavy metal storage disorders'''
| rowspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Heavy metal storage disorders'''
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Hemochromatosis'''<ref name="pmid24741460">{{cite journal |vauthors=Jeong HK, An JH, Kim HS, Cho EA, Han MG, Moon JS, Kim HK, Kang HC |title=Hypoparathyroidism and subclinical hypothyroidism with secondary hemochromatosis |journal=Endocrinol Metab (Seoul) |volume=29 |issue=1 |pages=91–5 |year=2014 |pmid=24741460 |pmc=3970271 |doi=10.3803/EnM.2014.29.1.91 |url=}}</ref><ref name="urlhereditary hemochromatosis - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis |title=hereditary hemochromatosis - Genetics Home Reference |format= |work= |accessdate=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Hemochromatosis]]'''<ref name="pmid24741460">{{cite journal |vauthors=Jeong HK, An JH, Kim HS, Cho EA, Han MG, Moon JS, Kim HK, Kang HC |title=Hypoparathyroidism and subclinical hypothyroidism with secondary hemochromatosis |journal=Endocrinol Metab (Seoul) |volume=29 |issue=1 |pages=91–5 |year=2014 |pmid=24741460 |pmc=3970271 |doi=10.3803/EnM.2014.29.1.91 |url=}}</ref><ref name="urlhereditary hemochromatosis - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis |title=hereditary hemochromatosis - Genetics Home Reference |format= |work= |accessdate=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[HFE]] [[gene mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" |[[HFE]] [[gene mutation]]
Line 296: Line 325:
**[[Skin discoloration]]  
**[[Skin discoloration]]  
|-
|-
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''Wilson's disease'''<ref name="pmid6888480">{{cite journal |vauthors=Carpenter TO, Carnes DL, Anast CS |title=Hypoparathyroidism in Wilson's disease |journal=N. Engl. J. Med. |volume=309 |issue=15 |pages=873–7 |year=1983 |pmid=6888480 |doi=10.1056/NEJM198310133091501 |url=}}</ref><ref name="urlWilson disease - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/wilson-disease#definition |title=Wilson disease - Genetics Home Reference |format= |work= |accessdate=}}</ref>
| colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |'''[[Wilson's disease]]'''<ref name="pmid6888480">{{cite journal |vauthors=Carpenter TO, Carnes DL, Anast CS |title=Hypoparathyroidism in Wilson's disease |journal=N. Engl. J. Med. |volume=309 |issue=15 |pages=873–7 |year=1983 |pmid=6888480 |doi=10.1056/NEJM198310133091501 |url=}}</ref><ref name="urlWilson disease - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/wilson-disease#definition |title=Wilson disease - Genetics Home Reference |format= |work= |accessdate=}}</ref>
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[Autosomal recessive]]
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | ATP7B gene mutation
| style="padding: 5px 5px; background: #F5F5F5;" align="center" | [[ATP7B]] [[gene]] [[mutation]]
| style="padding: 5px 5px; background: #F5F5F5;" |
| style="padding: 5px 5px; background: #F5F5F5;" |
*Clinical features of [[Wilson's disease]] include:
*Clinical features of [[Wilson's disease]] include:
**'''Initial feature'''
**Initial feature
***'''Children and young adults:''' [[Liver disease]]
***Children and young adults:[[Liver disease]]
***'''Adults:''' [[Nervous system disease|Nervous system disorders]] and [[Psychiatric Disorders|psychiatric disorders]]  
***Adults: [[Nervous system disease|Nervous system disorders]] and [[Psychiatric Disorders|psychiatric disorders]]  
*Other clinical features include:
*Other clinical features include:
**[[Clumsiness]]
**[[Clumsiness]]
Line 320: Line 349:
*[[Autoimmune polyendocrine syndrome type 1]]
*[[Autoimmune polyendocrine syndrome type 1]]
*[[Autosomal dominant hypocalcemia]] type 1
*[[Autosomal dominant hypocalcemia]] type 1
*[[Autosomal domina[[nt hypocalcemia]] type 2
*[[Autosomal dominant hypocalcemia]] type 2
*[[Bartter syndrome type 5
*Bartter syndrome type 5
*[[DiGeorge syndrome]]
*[[DiGeorge syndrome]]
*[[CHARGE syndrome]]
*[[CHARGE syndrome]]
*Kenny-Caffey syndrome type 1
*[[Kenny-Caffey syndrome type 1]]
*Kenny-Caffey syndrome type 2
*[[Kenny-Caffey syndrome type 2]]
*Sanjad-Sakati syndrome
*[[Sanjad-Sakati syndrome]]
*[[Barakat syndrome]]
*[[Barakat syndrome]]
*[[Kearns–Sayre syndrome]]
*[[Kearns–Sayre syndrome]]
*Maternally inherited diabetes and deafness (MIDD)
*Maternally inherited [[diabetes]] and [[deafness]] (MIDD)
*Mitochondrial trifunctional protein deficiency (MTP deficiency)
*[[Mitochondrial trifunctional protein deficiency]] ([[MTP deficiency]])
*[[Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency]] ([[LCHAD deficiency]])
*[[Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency]] ([[LCHAD deficiency]])
*[[Hemochromatosis]]
*[[Hemochromatosis]]
Line 346: Line 375:
{{WH}}
{{WH}}
{{WS}}
{{WS}}
[[Category:Disease]]
[[Category:Medicine]]
[[Category:Endocrinology]]
[[Category:Parathyroid disorders]]
[[Category:Up-To-Date]]

Latest revision as of 22:18, 29 July 2020

Hypoparathyroidism Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

Hypoparathyroidism is a decrease in serum parathyroid hormone. Normally, parathyroid hormone increases serum calcium and magnesium concentration, and decreases serum phosphate concentration. Secretion of parathyroid hormone from parathyroid gland is stimulated by low serum calcium. Parathyroid glands have calcium-sensing receptors responsible for sensing extracellular ionized calcium. Calcium and magnesium provides a negative feedback for secretion of parathyroid hormone. Deficiency of parathyroid hormone causes body to decrease reabsorption of calcium from bone, excretion of phosphate, reabsorbtion of calcium from distal tubules, and vitamin D mediated absorption of calcium from intestine leading to hypocalcemia. Many genetic conditions are associated with hypoparathyroidism. Hypoparathyroidism associated with genetic defects may be either autoimmune hypoparathyroidism, isolated hypoparathyroidism, associated with congenital multisystem syndromes, or a part of metabolic disorders.

Pathophysiology

Parathyroid, Vitamin D, and Mineral Homeostasis

The effect of parathyroid hormone on mineral metabolism is as follows:[1][2]

Effect of minerals and vitamin D on parathyroid hormone:







The Sequence of Events in Parathyroid, Vitamin D, and Mineral Homeostasis


 
 
 
 
 
 
 
 
 
 
 
Parathyroid hormone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Kidney
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Decreased excretion of magnesium
 
 
 
Increasead conversion of inactive 25-hydroyx vitamin D to the active 1,25-dihydroy xvitamin D
 
 
Increase excretion of inorganic phosphate
 
 
 
 
Decrease excretion of calcium
 
 
 
 
 
Increased resorption of bone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Increased serum concentration of magnesium
 
 
 
Increased absorption of calcium from gut
 
 
Decreased serum concentration of inorganic phosphate
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prevents precipitation of calcium phosphate in bones
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Increased serum concentration of calcium
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Calcium-sensing receptors


Pathogenesis




 
 
 
 
 
 
 
 
 
Hypoparathyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Deficiency of parathyroid hormone
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Decrease reabsorption of calcium from bone
 
 
Decrease excretion of phosphate
 
 
 
Decrease reabsorbtion of calcium from distal tubules
 
 
Decrease vitamin D mediated absorption of calcium from intestine
 


Post-surgical Hypoparathyroidism

  • Anterior neck surgery most commonly causes hypoparathyroidism. Majority of time this hypoparathyroidism is transient i.e. it resolves within 6 months.[5][6][7]
  • The features of hypoparathyroidism should persist for atleast 6 month after surgery to be diagnosed as chronic hypoparathyroidism.
  • 30–60% Patients undergoing total thyroidectomy develops hypocalcaemia within 24 hours as an initial manifestation of postoperative parathyroid failure. About 60%-70% of these cases resolve within 4–6 weeks after surgery. Remaining cases progress to develop protracted hypoparathyroidism requiring continuous treatment. Around 15–25% of patients with protracted hypoparathyroidism progress to chronic hypoparathyroidism.[8]
  • Factors favorring recovery from protracted hypoparathyroidism include:
    • Number of parathyroid glands remaining in situ.
    • Serum calcium level at this stage : There is high rate of recovery in individuals whose calcium levels are normal to elevated one month postoperatively.

Genetics

Genetics of Hypoparathyroidism
Hypoparathyroidism Inheritance Gene mutation Clinical features
Autoimmune Autoimmune polyglandular hypoparathyroidism Autoimmune polyendocrine syndrome type 1[9] Autosomal recessive Mutation in AIRE gene
Isolated Familial Isolated hypoparathyroidism Autosomal dominant PTH gene[10]
Glial cells missing GCM2 gene[11]
Autosomal recessive PTH gene[12]
Glial cells missing 2 (GCM2) gene[11][13]
X-linked FHL1 gene (exon 4, c.C283T, p.R95W) on chromosome locus Xq26-q27[14]
Autosomal dominant hypercalcemia[15] Autosomal dominant hypocalcemia type 1 Autosomal dominant Calcium-sensing receptor gene mutation
NOTE: Calcium-sensing receptor gene activating mutation can also cause mild Bartter syndrome type 5. This mutation cause the inhibition of apical potassium channel in the thick ascending limb of the loop of Henle in the kidney.[16][17]
Autosomal dominant hypocalcemia type 2 Autosomal dominant G protein G11 (GNA11) mutation
Congenital multisystem syndromes DiGeorge syndrome[18] Autosomal dominant 22q11.2 deletion
CHARGE syndrome[19] Autosomal dominant CHD7 G744S missense mutation
Kenny-Caffey syndrome type 1[20] Autosomal recessive Deletion of the TBCE gene
Kenny-Caffey syndrome type 2[21] Autosomal dominant Mutation of “family with sequence similarity 111, member A″ (FAM111A) gene located on chromosome locus 11q12.1
Sanjad-Sakati syndrome[22] Autosomal recessive Mutation in TBCE gene
Barakat syndrome[23][24] Autosomal recessive Mutations in the GATA3 gene
Metabolic diseases Mitochondiral polyneuropathies[25] Kearns–Sayre syndrome Mitochondrial inheritence mtDNA deletion
Maternally inherited diabetes and deafness (MIDD) Mitochondrial inheritence MT‑TL1 defect
Mitochondrial enzyme deficiencies Mitochondrial trifunctional protein deficiency (MTP deficiency)[26][27] Autosomal recessive HADHA or HADHB gene mutation
Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency (LCHAD deficiency)[28] Autosomal recessive G1528C gene mutation
Heavy metal storage disorders Hemochromatosis[29][30] Autosomal recessive HFE gene mutation
Wilson's disease[31][32] Autosomal recessive ATP7B gene mutation

Associated Conditions

Conditions associated with hypoparathyroidism include:[9][15][16][17][18][19][20][21][22][23][24][25][26][28][29][31]

Gross Pathology

  • There is no gross pathology findings for hypoparathyroidism.

Microscopic Pathology

  • There is no microscopic pathology findings for hypoparathyroidism.

References

  1. HARRISON MT (1964). "INTERRELATIONSHIPS OF VITAMIN D AND PARATHYROID HORMONE IN CALCIUM HOMEOSTASIS". Postgrad Med J. 40: 497–505. PMC 2482768. PMID 14184232.
  2. Nussey, Stephen (2001). Endocrinology : an integrated approach. Oxford, UK Bethesda, Md: Bios NCBI. ISBN 1-85996-252-1.
  3. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O; et al. (1993). "Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid". Nature. 366 (6455): 575–80. doi:10.1038/366575a0. PMID 8255296.
  4. Brown EM, Pollak M, Seidman CE, Seidman JG, Chou YH, Riccardi D; et al. (1995). "Calcium-ion-sensing cell-surface receptors". N Engl J Med. 333 (4): 234–40. doi:10.1056/NEJM199507273330407. PMID 7791841.
  5. Bilezikian JP, Khan A, Potts JT, Brandi ML, Clarke BL, Shoback D, Jüppner H, D'Amour P, Fox J, Rejnmark L, Mosekilde L, Rubin MR, Dempster D, Gafni R, Collins MT, Sliney J, Sanders J (2011). "Hypoparathyroidism in the adult: epidemiology, diagnosis, pathophysiology, target-organ involvement, treatment, and challenges for future research". J. Bone Miner. Res. 26 (10): 2317–37. doi:10.1002/jbmr.483. PMC 3405491. PMID 21812031.
  6. Ritter K, Elfenbein D, Schneider DF, Chen H, Sippel RS (2015). "Hypoparathyroidism after total thyroidectomy: incidence and resolution". J. Surg. Res. 197 (2): 348–53. doi:10.1016/j.jss.2015.04.059. PMC 4466142. PMID 25982044.
  7. Sturniolo G, Lo Schiavo MG, Tonante A, D'Alia C, Bonanno L (2000). "Hypocalcemia and hypoparathyroidism after total thyroidectomy: a clinical biological study and surgical considerations". Int. J. Surg. Investig. 2 (2): 99–105. PMID 12678507.
  8. Bollerslev J, Rejnmark L, Marcocci C, Shoback DM, Sitges-Serra A, van Biesen W, Dekkers OM (2015). "European Society of Endocrinology Clinical Guideline: Treatment of chronic hypoparathyroidism in adults". Eur. J. Endocrinol. 173 (2): G1–20. doi:10.1530/EJE-15-0628. PMID 26160136.
  9. 9.0 9.1 Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J (1990). "Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients". N. Engl. J. Med. 322 (26): 1829–36. doi:10.1056/NEJM199006283222601. PMID 2348835.
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