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Autosomal dominant hypocalcemia

MedGen UID:
884527
Concept ID:
C4048195
Disease or Syndrome
Synonym: HYPOCALCEMIA, FAMILIAL
SNOMED CT: Autosomal dominant hypocalcemia (711152006); Familial hypocalcemia (711152006); Familial hypercalciuric hypocalcemia (711152006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Monarch Initiative: MONDO:0018543
OMIM®: 601198
OMIM® Phenotypic series: PS601198
Orphanet: ORPHA428

Definition

Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems.

The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or tingling sensations (paresthesias), or twitching of the nerves and muscles (neuromuscular irritability) in various parts of the body. More severely affected individuals develop seizures, usually in infancy or childhood. Sometimes, these symptoms occur only during episodes of illness or fever.

Some people with autosomal dominant hypocalcemia have high levels of calcium in their urine (hypercalciuria), which can lead to deposits of calcium in the kidneys (nephrocalcinosis) or the formation of kidney stones (nephrolithiasis). These conditions can damage the kidneys and impair their function. Sometimes, abnormal deposits of calcium form in the brain, typically in structures called basal ganglia, which help control movement.

A small percentage of severely affected individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include a shortage of potassium (hypokalemia) and magnesium and a buildup of the hormone aldosterone (hyperaldosteronism) in the blood. The abnormal balance of molecules can raise the pH of the blood, which is known as metabolic alkalosis. The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V.

There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same. [from MedlinePlus Genetics]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal dominant hypocalcemia

Professional guidelines

PubMed

Rejnmark L
Endocrinol Metab (Seoul) 2024 Apr;39(2):262-266. Epub 2024 Apr 4 doi: 10.3803/EnM.2024.1916. PMID: 38572533Free PMC Article
Winer KK
Bone 2019 Mar;120:535-541. Epub 2018 Sep 21 doi: 10.1016/j.bone.2018.09.018. PMID: 30243992
Tabacco G, Bilezikian JP
Endocrinol Metab Clin North Am 2018 Dec;47(4):901-915. doi: 10.1016/j.ecl.2018.07.013. PMID: 30390821

Recent clinical studies

Etiology

Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
Tőke J, Czirják G, Enyedi P, Tóth M
Endocrine 2021 Mar;71(3):611-617. Epub 2021 Feb 2 doi: 10.1007/s12020-021-02620-5. PMID: 33528764Free PMC Article
Dershem R, Gorvin CM, Metpally RPR, Krishnamurthy S, Smelser DT, Hannan FM, Carey DJ, Thakker RV, Breitwieser GE; Regeneron Genetics Center
Am J Hum Genet 2020 Jun 4;106(6):734-747. Epub 2020 May 7 doi: 10.1016/j.ajhg.2020.04.006. PMID: 32386559Free PMC Article
Winer KK
Bone 2019 Mar;120:535-541. Epub 2018 Sep 21 doi: 10.1016/j.bone.2018.09.018. PMID: 30243992
Mayr B, Glaudo M, Schöfl C
Trends Endocrinol Metab 2016 Sep;27(9):643-652. Epub 2016 Jun 20 doi: 10.1016/j.tem.2016.05.005. PMID: 27339034

Diagnosis

Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
Tőke J, Czirják G, Enyedi P, Tóth M
Endocrine 2021 Mar;71(3):611-617. Epub 2021 Feb 2 doi: 10.1007/s12020-021-02620-5. PMID: 33528764Free PMC Article
Dershem R, Gorvin CM, Metpally RPR, Krishnamurthy S, Smelser DT, Hannan FM, Carey DJ, Thakker RV, Breitwieser GE; Regeneron Genetics Center
Am J Hum Genet 2020 Jun 4;106(6):734-747. Epub 2020 May 7 doi: 10.1016/j.ajhg.2020.04.006. PMID: 32386559Free PMC Article
Cianferotti L, Marcucci G, Brandi ML
Best Pract Res Clin Endocrinol Metab 2018 Dec;32(6):909-925. Epub 2018 Jul 29 doi: 10.1016/j.beem.2018.07.001. PMID: 30665552
Vahe C, Benomar K, Espiard S, Coppin L, Jannin A, Odou MF, Vantyghem MC
Orphanet J Rare Dis 2017 Jan 25;12(1):19. doi: 10.1186/s13023-017-0570-z. PMID: 28122587Free PMC Article

Therapy

Rejnmark L
Endocrinol Metab (Seoul) 2024 Apr;39(2):262-266. Epub 2024 Apr 4 doi: 10.3803/EnM.2024.1916. PMID: 38572533Free PMC Article
Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
Winer KK
Bone 2019 Mar;120:535-541. Epub 2018 Sep 21 doi: 10.1016/j.bone.2018.09.018. PMID: 30243992
Cianferotti L, Marcucci G, Brandi ML
Best Pract Res Clin Endocrinol Metab 2018 Dec;32(6):909-925. Epub 2018 Jul 29 doi: 10.1016/j.beem.2018.07.001. PMID: 30665552
Siraj N, Hakami Y, Khan A
Endocrinol Metab Clin North Am 2018 Dec;47(4):797-808. Epub 2018 Oct 11 doi: 10.1016/j.ecl.2018.07.006. PMID: 30390814

Prognosis

Howles SA, Gorvin CM, Cranston T, Rogers A, Gluck AK, Boon H, Gibson K, Rahman M, Root A, Nesbit MA, Hannan FM, Thakker RV
J Bone Miner Res 2023 Jun;38(6):907-917. Epub 2023 Apr 18 doi: 10.1002/jbmr.4803. PMID: 36970776Free PMC Article
Dershem R, Gorvin CM, Metpally RPR, Krishnamurthy S, Smelser DT, Hannan FM, Carey DJ, Thakker RV, Breitwieser GE; Regeneron Genetics Center
Am J Hum Genet 2020 Jun 4;106(6):734-747. Epub 2020 May 7 doi: 10.1016/j.ajhg.2020.04.006. PMID: 32386559Free PMC Article
Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, Gelb J, Krusinska E, Brennan SC, Schepelmann M, Riccardi D, Bin Khayat ME, Ward DT, Nemeth EF, Rosskamp R, Collins MT
J Bone Miner Res 2019 Sep;34(9):1609-1618. Epub 2019 Jul 26 doi: 10.1002/jbmr.3747. PMID: 31063613Free PMC Article
Nesbit MA, Hannan FM, Howles SA, Babinsky VN, Head RA, Cranston T, Rust N, Hobbs MR, Heath H 3rd, Thakker RV
N Engl J Med 2013 Jun 27;368(26):2476-2486. doi: 10.1056/NEJMoa1300253. PMID: 23802516Free PMC Article
Silve C, Petrel C, Leroy C, Bruel H, Mallet E, Rognan D, Ruat M
J Biol Chem 2005 Nov 11;280(45):37917-23. Epub 2005 Sep 7 doi: 10.1074/jbc.M506263200. PMID: 16147994

Clinical prediction guides

Dimke H
Curr Opin Nephrol Hypertens 2024 Jul 1;33(4):433-440. Epub 2024 May 1 doi: 10.1097/MNH.0000000000000998. PMID: 38690798
Howles SA, Gorvin CM, Cranston T, Rogers A, Gluck AK, Boon H, Gibson K, Rahman M, Root A, Nesbit MA, Hannan FM, Thakker RV
J Bone Miner Res 2023 Jun;38(6):907-917. Epub 2023 Apr 18 doi: 10.1002/jbmr.4803. PMID: 36970776Free PMC Article
Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article
van Megen WH, Tan RSG, Alexander RT, Dimke H
EBioMedicine 2022 Apr;78:103947. Epub 2022 Mar 18 doi: 10.1016/j.ebiom.2022.103947. PMID: 35313217Free PMC Article
Roberts MS, Gafni RI, Brillante B, Guthrie LC, Streit J, Gash D, Gelb J, Krusinska E, Brennan SC, Schepelmann M, Riccardi D, Bin Khayat ME, Ward DT, Nemeth EF, Rosskamp R, Collins MT
J Bone Miner Res 2019 Sep;34(9):1609-1618. Epub 2019 Jul 26 doi: 10.1002/jbmr.3747. PMID: 31063613Free PMC Article

Recent systematic reviews

Roszko KL, Stapleton Smith LM, Sridhar AV, Roberts MS, Hartley IR, Gafni RI, Collins MT, Fox JC, Nemeth EF
J Bone Miner Res 2022 Oct;37(10):1926-1935. Epub 2022 Aug 22 doi: 10.1002/jbmr.4659. PMID: 35879818Free PMC Article

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