MCID: HYP599
MIFTS: 37

Hypoparathyroidism, Familial Isolated

Categories: Genetic diseases, Rare diseases, Eye diseases, Endocrine diseases

Aliases & Classifications for Hypoparathyroidism, Familial Isolated

MalaCards integrated aliases for Hypoparathyroidism, Familial Isolated:

Name: Hypoparathyroidism, Familial Isolated 57 75
Hypoparathyroidism Familial Isolated 53 29 6 73
Hypoparathyroidism, Autosomal Recessive 57 29 73
Fih 57 75
Familial Isolated Hypoparathyroidism Due to Impaired Pth Secretion 59
Hypoparathyroidism - Autosomal Dominant 73
Hypoparathyroidism, Autosomal Dominant 57
Autosomal Recessive Hypoparathyroidism 75
Autosomal Dominant Hypoparathyroidism 75
Familial Isolated Hypoparathyroidism 59

Characteristics:

Orphanet epidemiological data:

59
familial isolated hypoparathyroidism due to impaired pth secretion
Inheritance: Autosomal dominant,Autosomal recessive;
familial isolated hypoparathyroidism
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
hypoparathyroidism, familial isolated:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Hypoparathyroidism, Familial Isolated

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2238Disease definitionFamilial isolated hypoparathyroidism (FIH) is a rare heterogeneous group of metabolic disorders characterized by abnormal calcium metabolism due to deficient secretion of parathormone (PTH), without other endocrine disorders or developmental defects. It can occur at any age (from the newborn period to adulthood) but generally starts within the first decade of life. The clinical signs are mainly those of hypocalcemia: myopathy, muscular weakness, cramps, tetany, lenticular cataracts, teeth anomalies and short stature. Isolated hypoparathyroidism may be sporadic or familial, with autosomal dominant or recessive inheritance. FIH may be due to an activating mutation of the calcium-sensing receptor (CASR) gene. This is the most common cause of genetic hypoparathyroidism and is transmitted as an autosomal dominant trait. It represents 42% of isolated hypoparathyroidism cases. Thirteen mutations have been described in familial or sporadic cases. In three families, mutations in the PTH gene have been identified. This type of FIH is transmitted as an autosomal recessive or dominant trait. One family has been reported with a mutation in the gene encoding the glial cells missing homolog b (GCMB) transcription factor. In this case, transmission is autosomal recessive. Diagnosis is made when hypocalcemia, hyperphosphoremia, and low or undetectable PTH levels are observed. Management consists of symptomatic treatment with supplementary calcium and vitamin D.Visit the Orphanet disease page for more resources.

MalaCards based summary : Hypoparathyroidism, Familial Isolated, also known as hypoparathyroidism familial isolated, is related to hypocalcemia, autosomal dominant 1 and hypoparathyroidism. An important gene associated with Hypoparathyroidism, Familial Isolated is PTH (Parathyroid Hormone), and among its related pathways/superpathways is Parathyroid hormone synthesis, secretion and action. Affiliated tissues include thymus, eye and bone, and related phenotypes are nephropathy and cataract

OMIM : 57 Garfield and Karaplis (2001) reviewed the various causes and clinical forms of hypoparathyroidism. They noted that hypoparathyroidism is a clinical disorder characterized by hypocalcemia and hyperphosphatemia. It manifests when parathyroid hormone (PTH; 168450) secreted from the parathyroid glands is insufficient to maintain normal extracellular fluid calcium concentrations or, less commonly, when PTH is unable to function optimally in target tissues, despite adequate circulating levels. Congenital absence of the parathyroid and thymus glands (III and IV pharyngeal pouch syndrome, or DiGeorge syndrome, 188400) is usually a sporadic condition (Taitz et al., 1966). (146200)

UniProtKB/Swiss-Prot : 75 Hypoparathyroidism, familial isolated: A disorder characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Clinical features include seizures, tetany and cramps.

Related Diseases for Hypoparathyroidism, Familial Isolated

Diseases in the Hypoparathyroidism, Familial Isolated family:

Familial Isolated Hypoparathyroidism Due to Agenesis of Parathyroid Gland

Diseases related to Hypoparathyroidism, Familial Isolated via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 34)
# Related Disease Score Top Affiliating Genes
1 hypocalcemia, autosomal dominant 1 31.4 CASR GCM2
2 hypoparathyroidism 27.4 AIRE CASR GCM2 PTH
3 familial isolated hypoparathyroidism due to agenesis of parathyroid gland 12.1
4 hypoxia 10.4
5 autoimmune polyendocrine syndrome type 1 9.9 AIRE CASR
6 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 9.9 AIRE CASR
7 colorectal cancer 9.8
8 renal cell carcinoma, nonpapillary 9.8
9 ovarian cancer 9.8
10 patent foramen ovale 9.8
11 clear cell renal cell carcinoma 9.8
12 pancreatitis 9.8
13 autoimmune polyendocrine syndrome 9.8 AIRE CASR
14 chief cell adenoma 9.8 GCM2 PTH
15 hypocalciuric hypercalcemia, familial, type iii 9.6 CASR PTH
16 calciphylaxis 9.6 CASR PTH
17 hypercalcemia, infantile, 1 9.6 CASR PTH
18 osteitis fibrosa 9.6 CASR PTH
19 hypocalciuric hypercalcemia, familial, type ii 9.6 CASR PTH
20 familial hypocalciuric hypercalcemia 9.6 CASR PTH
21 phosphorus metabolism disease 9.5 CASR PTH
22 secondary hyperparathyroidism of renal origin 9.5 CASR PTH
23 renal osteodystrophy 9.5 CASR PTH
24 mineral metabolism disease 9.4 CASR PTH
25 parathyroid carcinoma 9.4 CASR PTH
26 uremia 9.3 CASR PTH
27 multiple endocrine neoplasia, type i 9.2 CASR PTH
28 chronic kidney failure 9.1 CASR PTH
29 hyperphosphatemia 9.0 CASR GCM2 PTH
30 parathyroid adenoma 9.0 CASR GCM2 PTH
31 primary hyperparathyroidism 9.0 CASR GCM2 PTH
32 hyperparathyroidism 9.0 CASR GCM2 PTH
33 bone disease 8.9 CASR PTH
34 parathyroid gland disease 8.4 AIRE CASR GCM2 PTH

Graphical network of the top 20 diseases related to Hypoparathyroidism, Familial Isolated:



Diseases related to Hypoparathyroidism, Familial Isolated

Symptoms & Phenotypes for Hypoparathyroidism, Familial Isolated

Symptoms via clinical synopsis from OMIM:

57
Neuro:
seizures
chronic tetany

Lab:
hypocalcemia
hyperphosphatemia
no circulating antibodies to parathyroid hormone
undetectable or subnormal plasma immunoreactive pth

Radiology:
intracerebral calcification on ct scan

Endocrine:
hypoparathyroidism

Eyes:
cataracts


Clinical features from OMIM:

146200

Human phenotypes related to Hypoparathyroidism, Familial Isolated:

59 32 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nephropathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000112
2 cataract 59 32 frequent (33%) Frequent (79-30%) HP:0000518
3 abnormality of dental enamel 59 32 frequent (33%) Frequent (79-30%) HP:0000682
4 delayed eruption of teeth 59 32 frequent (33%) Frequent (79-30%) HP:0000684
5 hypoparathyroidism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000829
6 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
7 cerebral calcification 59 32 frequent (33%) Frequent (79-30%) HP:0002514
8 hypocalcemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002901
9 myopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0003198
10 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
11 arrhythmia 59 32 frequent (33%) Frequent (79-30%) HP:0011675
12 abnormality of calcium-phosphate metabolism 59 32 hallmark (90%) Very frequent (99-80%) HP:0100530
13 tetany 32 HP:0001281
14 hyperphosphatemia 32 HP:0002905

MGI Mouse Phenotypes related to Hypoparathyroidism, Familial Isolated:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 8.92 AIRE CASR GCM2 PTH

Drugs & Therapeutics for Hypoparathyroidism, Familial Isolated

Search Clinical Trials , NIH Clinical Center for Hypoparathyroidism, Familial Isolated

Genetic Tests for Hypoparathyroidism, Familial Isolated

Genetic tests related to Hypoparathyroidism, Familial Isolated:

# Genetic test Affiliating Genes
1 Hypoparathyroidism Familial Isolated 29 GCM2 PTH
2 Hypoparathyroidism, Autosomal Recessive 29

Anatomical Context for Hypoparathyroidism, Familial Isolated

MalaCards organs/tissues related to Hypoparathyroidism, Familial Isolated:

41
Thymus, Eye, Bone

Publications for Hypoparathyroidism, Familial Isolated

Articles related to Hypoparathyroidism, Familial Isolated:

# Title Authors Year
1
Bone Status Among Patients With Nonsurgical Hypoparathyroidism, Autosomal Dominant Hypocalcaemia, and Pseudohypoparathyroidism: A Cohort Study. ( 29087612 )
2017

Variations for Hypoparathyroidism, Familial Isolated

UniProtKB/Swiss-Prot genetic disease variations for Hypoparathyroidism, Familial Isolated:

75
# Symbol AA change Variation ID SNP ID
1 GCM2 p.Arg47Leu VAR_058044 rs104893959
2 GCM2 p.Gly63Ser VAR_058045 rs104893960
3 GCM2 p.Arg110Trp VAR_065495 rs780594439
4 GCM2 p.Asn502His VAR_065498 rs533942394
5 PTH p.Cys18Arg VAR_006047 rs104894271
6 PTH p.Ser23Pro VAR_018464 rs104894272

ClinVar genetic disease variations for Hypoparathyroidism, Familial Isolated:

6
(show top 50) (show all 184)
# Gene Variation Type Significance SNP ID Assembly Location
1 GCM2 GCM2, EX1-4DEL deletion Pathogenic
2 GCM2 NM_004752.3(GCM2): c.140G> T (p.Arg47Leu) single nucleotide variant Pathogenic rs104893959 GRCh37 Chromosome 6, 10877576: 10877576
3 GCM2 NM_004752.3(GCM2): c.140G> T (p.Arg47Leu) single nucleotide variant Pathogenic rs104893959 GRCh38 Chromosome 6, 10877343: 10877343
4 GCM2 NM_004752.3(GCM2): c.187G> A (p.Gly63Ser) single nucleotide variant Pathogenic rs104893960 GRCh37 Chromosome 6, 10877529: 10877529
5 GCM2 NM_004752.3(GCM2): c.187G> A (p.Gly63Ser) single nucleotide variant Pathogenic rs104893960 GRCh38 Chromosome 6, 10877296: 10877296
6 PTH NM_000315.3(PTH): c.52T> C (p.Cys18Arg) single nucleotide variant Pathogenic rs104894271 GRCh37 Chromosome 11, 13514351: 13514351
7 PTH NM_000315.3(PTH): c.52T> C (p.Cys18Arg) single nucleotide variant Pathogenic rs104894271 GRCh38 Chromosome 11, 13492804: 13492804
8 PTH PTH, IVS2DS, G-C, +1, EX2DEL deletion Pathogenic
9 PTH NM_000315.3(PTH): c.67T> C (p.Ser23Pro) single nucleotide variant Pathogenic rs104894272 GRCh37 Chromosome 11, 13514336: 13514336
10 PTH NM_000315.3(PTH): c.67T> C (p.Ser23Pro) single nucleotide variant Pathogenic rs104894272 GRCh38 Chromosome 11, 13492789: 13492789
11 CASR NM_000388.3(CASR): c.1934C> A (p.Ala645Asp) single nucleotide variant Likely pathogenic rs193922430 GRCh37 Chromosome 3, 122002735: 122002735
12 CASR NM_000388.3(CASR): c.1934C> A (p.Ala645Asp) single nucleotide variant Likely pathogenic rs193922430 GRCh38 Chromosome 3, 122283888: 122283888
13 GCM2 NM_004752.3(GCM2): c.893delT (p.Ile298Thrfs) deletion Pathogenic rs886037646 GRCh37 Chromosome 6, 10874856: 10874856
14 GCM2 NM_004752.3(GCM2): c.893delT (p.Ile298Thrfs) deletion Pathogenic rs886037646 GRCh38 Chromosome 6, 10874623: 10874623
15 CASR NM_000388.3(CASR): c.78C> G (p.Ala26=) single nucleotide variant Benign rs77852524 GRCh37 Chromosome 3, 121973114: 121973114
16 CASR NM_000388.3(CASR): c.78C> G (p.Ala26=) single nucleotide variant Benign rs77852524 GRCh38 Chromosome 3, 122254267: 122254267
17 CASR NM_000388.3(CASR): c.748G> A (p.Glu250Lys) single nucleotide variant Benign/Likely benign rs62269092 GRCh37 Chromosome 3, 121980630: 121980630
18 CASR NM_000388.3(CASR): c.748G> A (p.Glu250Lys) single nucleotide variant Benign/Likely benign rs62269092 GRCh38 Chromosome 3, 122261783: 122261783
19 CASR NM_000388.3(CASR): c.2610G> A (p.Glu870=) single nucleotide variant Benign rs143738711 GRCh37 Chromosome 3, 122003411: 122003411
20 CASR NM_000388.3(CASR): c.2610G> A (p.Glu870=) single nucleotide variant Benign rs143738711 GRCh38 Chromosome 3, 122284564: 122284564
21 CASR NM_001178065.1(CASR): c.2998A> G (p.Arg1000Gly) single nucleotide variant Benign rs1042636 GRCh37 Chromosome 3, 122003769: 122003769
22 CASR NM_001178065.1(CASR): c.2998A> G (p.Arg1000Gly) single nucleotide variant Benign rs1042636 GRCh38 Chromosome 3, 122284922: 122284922
23 CASR NM_000388.3(CASR): c.573G> A (p.Glu191=) single nucleotide variant Benign/Likely benign rs141631116 GRCh37 Chromosome 3, 121980455: 121980455
24 CASR NM_000388.3(CASR): c.573G> A (p.Glu191=) single nucleotide variant Benign/Likely benign rs141631116 GRCh38 Chromosome 3, 122261608: 122261608
25 CASR NM_000388.3(CASR): c.762T> C (p.His254=) single nucleotide variant Likely benign rs76438850 GRCh37 Chromosome 3, 121980644: 121980644
26 CASR NM_000388.3(CASR): c.762T> C (p.His254=) single nucleotide variant Likely benign rs76438850 GRCh38 Chromosome 3, 122261797: 122261797
27 CASR NM_000388.3(CASR): c.1285C> T (p.His429Tyr) single nucleotide variant Benign/Likely benign rs142818334 GRCh37 Chromosome 3, 121981167: 121981167
28 CASR NM_000388.3(CASR): c.1285C> T (p.His429Tyr) single nucleotide variant Benign/Likely benign rs142818334 GRCh38 Chromosome 3, 122262320: 122262320
29 CASR NM_000388.3(CASR): c.1631G> A (p.Arg544Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs115230894 GRCh38 Chromosome 3, 122282135: 122282135
30 CASR NM_000388.3(CASR): c.1631G> A (p.Arg544Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs115230894 GRCh37 Chromosome 3, 122000982: 122000982
31 CASR NM_000388.3(CASR): c.1752G> A (p.Lys584=) single nucleotide variant Likely benign rs138638329 GRCh37 Chromosome 3, 122002553: 122002553
32 CASR NM_000388.3(CASR): c.1752G> A (p.Lys584=) single nucleotide variant Likely benign rs138638329 GRCh38 Chromosome 3, 122283706: 122283706
33 CASR NM_000388.3(CASR): c.1775A> G (p.Asn592Ser) single nucleotide variant Benign/Likely benign rs117375173 GRCh37 Chromosome 3, 122002576: 122002576
34 CASR NM_000388.3(CASR): c.1775A> G (p.Asn592Ser) single nucleotide variant Benign/Likely benign rs117375173 GRCh38 Chromosome 3, 122283729: 122283729
35 CASR NM_000388.3(CASR): c.2064C> T (p.Phe688=) single nucleotide variant Conflicting interpretations of pathogenicity rs150869744 GRCh37 Chromosome 3, 122002865: 122002865
36 CASR NM_000388.3(CASR): c.2064C> T (p.Phe688=) single nucleotide variant Conflicting interpretations of pathogenicity rs150869744 GRCh38 Chromosome 3, 122284018: 122284018
37 CASR NM_001178065.1(CASR): c.1763-9A> G single nucleotide variant Benign/Likely benign rs190731787 GRCh37 Chromosome 3, 122002525: 122002525
38 CASR NM_001178065.1(CASR): c.1763-9A> G single nucleotide variant Benign/Likely benign rs190731787 GRCh38 Chromosome 3, 122283678: 122283678
39 PTH NM_000315.3(PTH): c.247C> A (p.Arg83=) single nucleotide variant Benign rs6256 GRCh38 Chromosome 11, 13492506: 13492506
40 PTH NM_000315.3(PTH): c.247C> A (p.Arg83=) single nucleotide variant Benign rs6256 GRCh37 Chromosome 11, 13514053: 13514053
41 PTH NM_000315.3(PTH): c.-5-10G> A single nucleotide variant Benign rs694 GRCh38 Chromosome 11, 13492870: 13492870
42 PTH NM_000315.3(PTH): c.-5-10G> A single nucleotide variant Benign rs694 GRCh37 Chromosome 11, 13514417: 13514417
43 CASR NM_000388.3(CASR): c.1665T> C (p.Ile555=) single nucleotide variant Likely benign rs201955278 GRCh37 Chromosome 3, 122001016: 122001016
44 CASR NM_000388.3(CASR): c.1665T> C (p.Ile555=) single nucleotide variant Likely benign rs201955278 GRCh38 Chromosome 3, 122282169: 122282169
45 CASR NM_000388.3(CASR): c.1923C> T (p.Pro641=) single nucleotide variant Uncertain significance rs368093724 GRCh37 Chromosome 3, 122002724: 122002724
46 CASR NM_000388.3(CASR): c.1923C> T (p.Pro641=) single nucleotide variant Uncertain significance rs368093724 GRCh38 Chromosome 3, 122283877: 122283877
47 CASR NM_000388.3(CASR): c.2824G> A (p.Glu942Lys) single nucleotide variant Benign/Likely benign rs76327999 GRCh37 Chromosome 3, 122003625: 122003625
48 CASR NM_000388.3(CASR): c.2824G> A (p.Glu942Lys) single nucleotide variant Benign/Likely benign rs76327999 GRCh38 Chromosome 3, 122284778: 122284778
49 CASR NM_000388.3(CASR): c.2915C> T (p.Thr972Met) single nucleotide variant Conflicting interpretations of pathogenicity rs200620134 GRCh37 Chromosome 3, 122003716: 122003716
50 CASR NM_000388.3(CASR): c.2915C> T (p.Thr972Met) single nucleotide variant Conflicting interpretations of pathogenicity rs200620134 GRCh38 Chromosome 3, 122284869: 122284869

Expression for Hypoparathyroidism, Familial Isolated

Search GEO for disease gene expression data for Hypoparathyroidism, Familial Isolated.

Pathways for Hypoparathyroidism, Familial Isolated

Pathways related to Hypoparathyroidism, Familial Isolated according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.82 CASR GCM2 PTH

GO Terms for Hypoparathyroidism, Familial Isolated

Biological processes related to Hypoparathyroidism, Familial Isolated according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 9.33 AIRE GCM2 PTH
2 response to fibroblast growth factor GO:0071774 8.96 CASR PTH
3 cellular calcium ion homeostasis GO:0006874 8.8 CASR GCM2 PTH

Sources for Hypoparathyroidism, Familial Isolated

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
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34 ICD10 via Orphanet
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44 MeSH
45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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