FIH
MCID: HYP599
MIFTS: 40

Hypoparathyroidism, Familial Isolated (FIH)

Categories: Endocrine diseases, Eye diseases, Genetic diseases, Rare 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.Clinical descriptionIt can occur at any age (from the newborn period to adulthood) but generally starts within the first decade of life. Diagnosis is made when hypocalcemia, hyperphosphoremia, and low or undetectable PTH levels are observed. The clinical signs are mainly those of hypocalcemia: myopathy, muscular weakness, cramps, tetany, lenticular cataracts, teeth anomalies and short stature.EtiologyFIH 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 dominanttrait. 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.Genetic counselingIsolated hypoparathyroidism may be sporadic or familial, with autosomal dominant or recessive inheritance.Management and treatmentManagement 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 seizures and cerebral calcification

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 45)
# Related Disease Score Top Affiliating Genes
1 hypocalcemia, autosomal dominant 1 31.3 CASR GCM2 PTH
2 hypoparathyroidism 29.0 AIRE CASR GCM2 PTH
3 familial isolated hypoparathyroidism due to agenesis of parathyroid gland 12.2
4 hypoxia 10.5
5 colorectal cancer 10.0
6 renal cell carcinoma, nonpapillary 10.0
7 ovarian cancer 10.0
8 legionnaires' disease 10.0
9 patent foramen ovale 10.0
10 clear cell renal cell carcinoma 10.0
11 autoimmune progesterone dermatitis 10.0
12 autoimmune polyendocrine syndrome 10.0 AIRE CASR
13 autoimmune polyendocrine syndrome type 1 10.0 AIRE CASR
14 autoimmune polyendocrine syndrome, type i, with or without reversible metaphyseal dysplasia 10.0 AIRE CASR
15 diabetes insipidus, nephrogenic, autosomal 10.0
16 osteoarthritis 10.0
17 diabetes insipidus 10.0
18 pseudohypoparathyroidism 10.0
19 chief cell adenoma 9.9 GCM2 PTH
20 hypocalciuric hypercalcemia, familial, type i 9.9 CASR PTH
21 hypocalciuric hypercalcemia, familial, type ii 9.9 CASR PTH
22 hypocalciuric hypercalcemia, familial, type iii 9.9 CASR PTH
23 calciphylaxis 9.9 CASR PTH
24 hypercalcemia, infantile, 1 9.9 CASR PTH
25 osteitis fibrosa 9.9 CASR PTH
26 familial hypocalciuric hypercalcemia 9.9 CASR PTH
27 phosphorus metabolism disease 9.9 CASR PTH
28 secondary hyperparathyroidism of renal origin 9.9 CASR PTH
29 metal metabolism disorder 9.8 CASR PTH
30 renal osteodystrophy 9.8 CASR PTH
31 mineral metabolism disease 9.8 CASR PTH
32 parathyroid carcinoma 9.8 CASR PTH
33 osteomalacia 9.8 CASR PTH
34 uremia 9.8 CASR PTH
35 multiple endocrine neoplasia, type i 9.8 CASR PTH
36 nephrocalcinosis 9.8 CASR PTH
37 nephrolithiasis 9.8 CASR PTH
38 chronic kidney failure 9.7 CASR PTH
39 familial isolated hyperparathyroidism 9.7 CASR GCM2 PTH
40 hyperparathyroidism 9.7 CASR GCM2 PTH
41 hyperphosphatemia 9.7 CASR GCM2 PTH
42 parathyroid adenoma 9.7 CASR GCM2 PTH
43 primary hyperparathyroidism 9.7 CASR GCM2 PTH
44 bone disease 9.6 CASR PTH
45 parathyroid gland disease 9.5 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 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 cerebral calcification 59 32 frequent (33%) Frequent (79-30%) HP:0002514
3 cataract 59 32 frequent (33%) Frequent (79-30%) HP:0000518
4 short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0004322
5 nephropathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0000112
6 myopathy 59 32 hallmark (90%) Very frequent (99-80%) HP:0003198
7 arrhythmia 59 32 frequent (33%) Frequent (79-30%) HP:0011675
8 delayed eruption of teeth 59 32 frequent (33%) Frequent (79-30%) HP:0000684
9 hypoparathyroidism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000829
10 abnormality of dental enamel 59 32 frequent (33%) Frequent (79-30%) HP:0000682
11 hypocalcemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002901
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
15 decreased circulating parathyroid hormone level 32 HP:0031817

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, Kidney

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 190)
# 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 CASR NM_001178065.1(CASR): c.2986G> T (p.Ala996Ser) single nucleotide variant Benign rs1801725 GRCh37 Chromosome 3, 122003757: 122003757
7 CASR NM_001178065.1(CASR): c.2986G> T (p.Ala996Ser) single nucleotide variant Benign rs1801725 GRCh38 Chromosome 3, 122284910: 122284910
8 PTH NM_000315.3(PTH): c.52T> C (p.Cys18Arg) single nucleotide variant Pathogenic rs104894271 GRCh37 Chromosome 11, 13514351: 13514351
9 PTH NM_000315.3(PTH): c.52T> C (p.Cys18Arg) single nucleotide variant Pathogenic rs104894271 GRCh38 Chromosome 11, 13492804: 13492804
10 PTH PTH, IVS2DS, G-C, +1, EX2DEL deletion Pathogenic
11 PTH NM_000315.3(PTH): c.67T> C (p.Ser23Pro) single nucleotide variant Pathogenic rs104894272 GRCh37 Chromosome 11, 13514336: 13514336
12 PTH NM_000315.3(PTH): c.67T> C (p.Ser23Pro) single nucleotide variant Pathogenic rs104894272 GRCh38 Chromosome 11, 13492789: 13492789
13 CASR NM_000388.3(CASR): c.1333A> G (p.Thr445Ala) single nucleotide variant Benign/Likely benign rs12493789 GRCh37 Chromosome 3, 121981215: 121981215
14 CASR NM_000388.3(CASR): c.1333A> G (p.Thr445Ala) single nucleotide variant Benign/Likely benign rs12493789 GRCh38 Chromosome 3, 122262368: 122262368
15 CASR NM_000388.3(CASR): c.1934C> A (p.Ala645Asp) single nucleotide variant Likely pathogenic rs193922430 GRCh37 Chromosome 3, 122002735: 122002735
16 CASR NM_000388.3(CASR): c.1934C> A (p.Ala645Asp) single nucleotide variant Likely pathogenic rs193922430 GRCh38 Chromosome 3, 122283888: 122283888
17 CASR NM_000388.3(CASR): c.2686delC (p.Arg896Alafs) deletion Uncertain significance rs193922438 GRCh37 Chromosome 3, 122003487: 122003487
18 CASR NM_000388.3(CASR): c.2686delC (p.Arg896Alafs) deletion Uncertain significance rs193922438 GRCh38 Chromosome 3, 122284640: 122284640
19 GCM2 NM_004752.3(GCM2): c.893delT (p.Ile298Thrfs) deletion Pathogenic rs886037646 GRCh37 Chromosome 6, 10874856: 10874856
20 GCM2 NM_004752.3(GCM2): c.893delT (p.Ile298Thrfs) deletion Pathogenic rs886037646 GRCh38 Chromosome 6, 10874623: 10874623
21 CASR NM_000388.3(CASR): c.78C> G (p.Ala26=) single nucleotide variant Benign rs77852524 GRCh37 Chromosome 3, 121973114: 121973114
22 CASR NM_000388.3(CASR): c.78C> G (p.Ala26=) single nucleotide variant Benign rs77852524 GRCh38 Chromosome 3, 122254267: 122254267
23 CASR NM_000388.3(CASR): c.748G> A (p.Glu250Lys) single nucleotide variant Benign/Likely benign rs62269092 GRCh37 Chromosome 3, 121980630: 121980630
24 CASR NM_000388.3(CASR): c.748G> A (p.Glu250Lys) single nucleotide variant Benign/Likely benign rs62269092 GRCh38 Chromosome 3, 122261783: 122261783
25 CASR NM_000388.3(CASR): c.2610G> A (p.Glu870=) single nucleotide variant Benign rs143738711 GRCh37 Chromosome 3, 122003411: 122003411
26 CASR NM_000388.3(CASR): c.2610G> A (p.Glu870=) single nucleotide variant Benign rs143738711 GRCh38 Chromosome 3, 122284564: 122284564
27 CASR NM_001178065.1(CASR): c.2998A> G (p.Arg1000Gly) single nucleotide variant Benign rs1042636 GRCh37 Chromosome 3, 122003769: 122003769
28 CASR NM_001178065.1(CASR): c.2998A> G (p.Arg1000Gly) single nucleotide variant Benign rs1042636 GRCh38 Chromosome 3, 122284922: 122284922
29 CASR NM_000388.3(CASR): c.573G> A (p.Glu191=) single nucleotide variant Benign/Likely benign rs141631116 GRCh37 Chromosome 3, 121980455: 121980455
30 CASR NM_000388.3(CASR): c.573G> A (p.Glu191=) single nucleotide variant Benign/Likely benign rs141631116 GRCh38 Chromosome 3, 122261608: 122261608
31 CASR NM_000388.3(CASR): c.762T> C (p.His254=) single nucleotide variant Likely benign rs76438850 GRCh37 Chromosome 3, 121980644: 121980644
32 CASR NM_000388.3(CASR): c.762T> C (p.His254=) single nucleotide variant Likely benign rs76438850 GRCh38 Chromosome 3, 122261797: 122261797
33 CASR NM_000388.3(CASR): c.1285C> T (p.His429Tyr) single nucleotide variant Benign/Likely benign rs142818334 GRCh37 Chromosome 3, 121981167: 121981167
34 CASR NM_000388.3(CASR): c.1285C> T (p.His429Tyr) single nucleotide variant Benign/Likely benign rs142818334 GRCh38 Chromosome 3, 122262320: 122262320
35 CASR NM_000388.3(CASR): c.1631G> A (p.Arg544Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs115230894 GRCh38 Chromosome 3, 122282135: 122282135
36 CASR NM_000388.3(CASR): c.1631G> A (p.Arg544Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs115230894 GRCh37 Chromosome 3, 122000982: 122000982
37 CASR NM_000388.3(CASR): c.1752G> A (p.Lys584=) single nucleotide variant Likely benign rs138638329 GRCh37 Chromosome 3, 122002553: 122002553
38 CASR NM_000388.3(CASR): c.1752G> A (p.Lys584=) single nucleotide variant Likely benign rs138638329 GRCh38 Chromosome 3, 122283706: 122283706
39 CASR NM_000388.3(CASR): c.1775A> G (p.Asn592Ser) single nucleotide variant Benign/Likely benign rs117375173 GRCh37 Chromosome 3, 122002576: 122002576
40 CASR NM_000388.3(CASR): c.1775A> G (p.Asn592Ser) single nucleotide variant Benign/Likely benign rs117375173 GRCh38 Chromosome 3, 122283729: 122283729
41 CASR NM_000388.3(CASR): c.2064C> T (p.Phe688=) single nucleotide variant Conflicting interpretations of pathogenicity rs150869744 GRCh37 Chromosome 3, 122002865: 122002865
42 CASR NM_000388.3(CASR): c.2064C> T (p.Phe688=) single nucleotide variant Conflicting interpretations of pathogenicity rs150869744 GRCh38 Chromosome 3, 122284018: 122284018
43 CASR NM_001178065.1(CASR): c.1763-9A> G single nucleotide variant Benign/Likely benign rs190731787 GRCh37 Chromosome 3, 122002525: 122002525
44 CASR NM_001178065.1(CASR): c.1763-9A> G single nucleotide variant Benign/Likely benign rs190731787 GRCh38 Chromosome 3, 122283678: 122283678
45 PTH NM_000315.3(PTH): c.247C> A (p.Arg83=) single nucleotide variant Benign rs6256 GRCh38 Chromosome 11, 13492506: 13492506
46 PTH NM_000315.3(PTH): c.247C> A (p.Arg83=) single nucleotide variant Benign rs6256 GRCh37 Chromosome 11, 13514053: 13514053
47 PTH NM_000315.3(PTH): c.-5-10G> A single nucleotide variant Benign rs694 GRCh38 Chromosome 11, 13492870: 13492870
48 PTH NM_000315.3(PTH): c.-5-10G> A single nucleotide variant Benign rs694 GRCh37 Chromosome 11, 13514417: 13514417
49 CASR NM_000388.3(CASR): c.1665T> C (p.Ile555=) single nucleotide variant Likely benign rs201955278 GRCh37 Chromosome 3, 122001016: 122001016
50 CASR NM_000388.3(CASR): c.1665T> C (p.Ile555=) single nucleotide variant Likely benign rs201955278 GRCh38 Chromosome 3, 122282169: 122282169

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
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11 DGIdb
17 ExPASy
19 FMA
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34 ICD10 via Orphanet
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44 MeSH
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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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