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Autosomal dominant hypocalcemia 1(HYPOC1)

MedGen UID:
87438
Concept ID:
C0342345
Disease or Syndrome
Synonyms: HYPOC1; HYPOCALCEMIA, FAMILIAL
SNOMED CT: Autosomal dominant hypoparathyroidism (711152006)
 
Gene (location): CASR (3q13.33-21.1)
 
Monarch Initiative: MONDO:0011013
OMIM®: 601198

Definition

Autosomal dominant hypocalcemia-1 is associated with low or normal serum parathyroid hormone concentrations (PTH). Approximately 50% of patients have mild or asymptomatic hypocalcemia; about 50% have paresthesias, carpopedal spasm, and seizures; about 10% have hypercalciuria with nephrocalcinosis or kidney stones; and more than 35% have ectopic and basal ganglia calcifications (summary by Nesbit et al., 2013). Thakker (2001) noted that patients with gain-of-function mutations in the CASR gene, resulting in generally asymptomatic hypocalcemia with hypercalciuria, have low-normal serum PTH concentrations and have often been diagnosed with hypoparathyroidism because of the insensitivity of earlier PTH assays. Because treatment with vitamin D to correct the hypocalcemia in these patients causes hypercalciuria, nephrocalcinosis, and renal impairment, these patients need to be distinguished from those with other forms of hypoparathyroidism (see 146200). Thakker (2001) suggested the designation 'autosomal dominant hypocalcemic hypercalciuria' for this CASR-related disorder. Genetic Heterogeneity of Autosomal Dominant Hypocalcemia Autosomal dominant hypocalcemia-2 (HYPOC2; 615361) is caused by mutation in the GNA11 gene (139313) on chromosome 19p13. [from OMIM]

Clinical features

From HPO
Hypercalciuria
MedGen UID:
43775
Concept ID:
C0020438
Finding
Abnormally high level of calcium in the urine.
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Decreased glomerular filtration rate
MedGen UID:
163428
Concept ID:
C0853068
Finding
An abnormal reduction in the volume of fluid filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Paresthesia
MedGen UID:
14619
Concept ID:
C0030554
Disease or Syndrome
Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Tetany
MedGen UID:
11748
Concept ID:
C0039621
Finding
A condition characterized by intermittent involuntary contraction of muscles (spasms) related to hypocalcemia or occasionally magnesium deficiency.
Basal ganglia calcification
MedGen UID:
234651
Concept ID:
C1389280
Pathologic Function
The presence of calcium deposition affecting one or more structures of the basal ganglia.
Laryngospasm
MedGen UID:
44071
Concept ID:
C0023066
Disease or Syndrome
A spasm (involuntary contraction) of the vocal cords that can make it difficult to speak or breathe.
Hypocalcemia
MedGen UID:
5705
Concept ID:
C0020598
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
Hypokalemia
MedGen UID:
5712
Concept ID:
C0020621
Finding
An abnormally decreased potassium concentration in the blood.
Hyperphosphatemia
MedGen UID:
39326
Concept ID:
C0085681
Disease or Syndrome
An abnormally increased phosphate concentration in the blood.
Hypomagnesemia
MedGen UID:
57481
Concept ID:
C0151723
Disease or Syndrome
An abnormally decreased magnesium concentration in the blood.
Decreased circulating parathyroid hormone level
MedGen UID:
1630961
Concept ID:
C0729198
Finding
An abnormally decreased concentration of parathyroid hormone.
Increased circulating renin level
MedGen UID:
66818
Concept ID:
C0240783
Finding
An increased level of renin in the blood.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal dominant hypocalcemia 1

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

Schreuder WH, Meijer EB, Cleven AHG, Edelenbos E, Klop C, Schreurs R, de Jong RT, van Maarle MC, Horsthuis RBG, de Lange J, van den Berg H
J Bone Miner Res 2023 Dec;38(12):1822-1833. Epub 2023 Nov 3 doi: 10.1002/jbmr.4922. PMID: 37823782
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
Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article
Stark Z, Savarirayan R
Orphanet J Rare Dis 2009 Feb 20;4:5. doi: 10.1186/1750-1172-4-5. PMID: 19232111Free PMC Article

Diagnosis

Berkešová BA, Borbély Z
Vnitr Lek 2023 Summer;69(E-3):16-19. doi: 10.36290/vnl.2023.036. PMID: 37468331
Vargas-Poussou R, Claverie-Martin F, Prot-Bertoye C, Carotti V, van der Wijst J, Perdomo-Ramirez A, Fraga-Rodriguez GM, Hureaux M, Bos C, Latta F, Houillier P, Hoenderop JGJ, de Baaij JHF
Nephrol Dial Transplant 2023 Feb 28;38(3):679-690. doi: 10.1093/ndt/gfac182. PMID: 35561741Free PMC Article
Jüppner H
J Clin Endocrinol Metab 2021 May 13;106(6):1541-1552. doi: 10.1210/clinem/dgab060. PMID: 33529330Free PMC Article
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
Stark Z, Savarirayan R
Orphanet J Rare Dis 2009 Feb 20;4:5. doi: 10.1186/1750-1172-4-5. PMID: 19232111Free PMC Article

Therapy

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
Winer KK
Bone 2019 Mar;120:535-541. Epub 2018 Sep 21 doi: 10.1016/j.bone.2018.09.018. PMID: 30243992
Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article
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
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

Schreuder WH, Meijer EB, Cleven AHG, Edelenbos E, Klop C, Schreurs R, de Jong RT, van Maarle MC, Horsthuis RBG, de Lange J, van den Berg H
J Bone Miner Res 2023 Dec;38(12):1822-1833. Epub 2023 Nov 3 doi: 10.1002/jbmr.4922. PMID: 37823782
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
Ji Y, Kang C, Chen J, Zhang L
Medicine (Baltimore) 2021 Jun 25;100(25):e26443. doi: 10.1097/MD.0000000000026443. PMID: 34160437Free 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
Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article

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
Jüppner H
J Clin Endocrinol Metab 2021 May 13;106(6):1541-1552. doi: 10.1210/clinem/dgab060. PMID: 33529330Free PMC Article
Winer KK, Kelly A, Johns A, Zhang B, Dowdy K, Kim L, Reynolds JC, Albert PS, Cutler GB Jr
J Pediatr 2018 Dec;203:391-399.e1. doi: 10.1016/j.jpeds.2018.08.010. PMID: 30470382Free 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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