MCID: FML068
MIFTS: 49

Familial Hypocalciuric Hypercalcemia

Categories: Rare diseases, Genetic diseases, Respiratory diseases, Bone diseases, Endocrine diseases, Fetal diseases, Metabolic diseases

Aliases & Classifications for Familial Hypocalciuric Hypercalcemia

MalaCards integrated aliases for Familial Hypocalciuric Hypercalcemia:

Name: Familial Hypocalciuric Hypercalcemia 12 49 55 36 36 28 14
Familial Benign Hypercalcemia 12 49 55 69
Fbhh 12 49 55
Fbh 12 49 55
Fhh 12 49 55
Familial Benign Hypocalciuric Hypercalcemia 12 55
Hypocalciuric Hypercalcemia, Familial, Type 1 69

Characteristics:

Orphanet epidemiological data:

55
familial hypocalciuric hypercalcemia
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: normal life expectancy;

Classifications:



External Ids:

Disease Ontology 12 DOID:0060699
ICD10 32 E83.5
Orphanet 55 ORPHA405
UMLS via Orphanet 70 C1809471
ICD10 via Orphanet 33 E83.5

Summaries for Familial Hypocalciuric Hypercalcemia

NIH Rare Diseases : 49 Familial hypocalciuric hypercalcemia (FHH) is a benign, inherited condition that causes abnormally high levels of calcium in the blood (hypercalcemia). Affected individuals usually do not have any signs or symptoms of the condition, and hypercalcemia is often diagnosed incidentally. In some individuals, weakness, fatigue, thought disturbance, and/or excessive thirst (polydipsia) have been reported. FHH is usually caused by mutations in the CASR gene, although abnormalities in other, unidentified genes have been documented. It is inherited in an autosomal dominant manner. Treatment is typically considered unnecessary because it is a benign condition. FHH can be difficult to distinguish from primary hyperparathyroidism, for which parathyroidectomy is typically performed; individuals with FHH are typically advised to avoid parathyroidectomy. Last updated: 9/23/2011

MalaCards based summary : Familial Hypocalciuric Hypercalcemia, also known as familial benign hypercalcemia, is related to hypocalciuric hypercalcemia, familial, type i and hypocalciuric hypercalcemia, familial, type iii, and has symptoms including hypocalciuria, reduced ratio of renal calcium clearance to creatinine clearance and parathormone-independent increased renal tubular calcium reabsorption. An important gene associated with Familial Hypocalciuric Hypercalcemia is CASR (Calcium Sensing Receptor), and among its related pathways/superpathways are Calcium signaling pathway and Endocrine and other factor-regulated calcium reabsorption. The drugs Plasminogen and Arginine Vasopressin have been mentioned in the context of this disorder. Affiliated tissues include bone, liver and kidney.

Disease Ontology : 12 A hypercalcemia characterized byautosomal dominant inheritance with elevation of serum calcium levels and decreased urinary calcium excretion.

Wikipedia : 72 Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a... more...

Related Diseases for Familial Hypocalciuric Hypercalcemia

Diseases in the Familial Hypocalciuric Hypercalcemia family:

Hypocalciuric Hypercalcemia, Familial, Type I Hypocalciuric Hypercalcemia, Familial, Type Ii
Hypocalciuric Hypercalcemia, Familial, Type Iii

Diseases related to Familial Hypocalciuric Hypercalcemia via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 43)
# Related Disease Score Top Affiliating Genes
1 hypocalciuric hypercalcemia, familial, type i 33.7 AP2S1 CASR GNA11
2 hypocalciuric hypercalcemia, familial, type iii 33.6 AP2S1 CASR GNA11
3 hypocalciuric hypercalcemia, familial, type ii 33.2 AP2S1 CASR GNA11 PTH
4 hypercalcemia, infantile, 1 31.8 CASR PTH
5 hyperparathyroidism 30.9 CASR CDC73 PTH
6 primary hyperparathyroidism 30.8 CASR CDC73 PTH
7 hypocalcemia, autosomal dominant 1 30.6 CASR GNA11
8 secondary hyperparathyroidism of renal origin 30.2 CASR PTH
9 chondrocalcinosis 30.1 AP2S1 CASR GNA11
10 hypoparathyroidism 29.9 CASR PTH SPG7
11 parathyroid adenoma 29.8 CASR CDC73 PTH
12 hyperparathyroidism, neonatal severe 11.5
13 osteitis fibrosa 10.3 CASR PTH
14 calciphylaxis 10.3 CASR PTH
15 pseudopseudohypoparathyroidism 10.3 GNA11 PTH
16 phosphorus metabolism disease 10.2 CASR PTH
17 hyperparathyroidism 2 with jaw tumors 10.2 CASR CDC73
18 renal osteodystrophy 10.2 CASR PTH
19 mineral metabolism disease 10.2 CASR PTH
20 hyperphosphatemia 10.1 CASR PTH
21 multiple endocrine neoplasia 10.1
22 endocrine organ benign neoplasm 10.1 CDC73 PTH
23 multiple endocrine neoplasia, type iia 10.0 CDC73 PTH
24 nuchal bleb, familial 10.0
25 parathyroid gland disease 10.0 CASR CDC73 PTH
26 parathyroid carcinoma 9.9 CASR CDC73 PTH
27 multiple endocrine neoplasia, type i 9.9 CASR CDC73 PTH
28 breast cancer 9.9
29 kabuki syndrome 1 9.9
30 alkaptonuria 9.9
31 hyperparathyroidism, primary, caused by water clear cell hyperplasia 9.9
32 insulinoma 9.9
33 rickets 9.9
34 neuroendocrine tumor 9.9
35 hyperostosis 9.9
36 adenoma 9.9
37 diffuse idiopathic skeletal hyperostosis 9.9
38 metastatic insulinoma 9.9
39 organ system benign neoplasm 9.9 CDC73 PTH
40 impaired renal function disease 9.9 ARHGAP4 PTH
41 uremia 9.8 CASR PTH
42 cell type benign neoplasm 9.8 CDC73 PTH
43 diabetes insipidus, nephrogenic, autosomal 9.8 ARHGAP4 CASR

Graphical network of the top 20 diseases related to Familial Hypocalciuric Hypercalcemia:



Diseases related to Familial Hypocalciuric Hypercalcemia

Symptoms & Phenotypes for Familial Hypocalciuric Hypercalcemia

Human phenotypes related to Familial Hypocalciuric Hypercalcemia:

55 31 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypocalciuria 55 31 obligate (100%) Obligate (100%) HP:0003127
2 reduced ratio of renal calcium clearance to creatinine clearance 55 31 hallmark (90%) Very frequent (99-80%) HP:0003513
3 parathormone-independent increased renal tubular calcium reabsorption 55 31 hallmark (90%) Very frequent (99-80%) HP:0003529
4 osteomalacia 55 31 frequent (33%) Frequent (79-30%) HP:0002749
5 infantile hypercalcemia 55 31 frequent (33%) Frequent (79-30%) HP:0008250
6 renal hypophosphatemia 55 31 frequent (33%) Frequent (79-30%) HP:0008732
7 chondrocalcinosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0000934
8 nausea and vomiting 55 31 occasional (7.5%) Occasional (29-5%) HP:0002017
9 headache 55 31 occasional (7.5%) Occasional (29-5%) HP:0002315
10 episodic abdominal pain 55 31 occasional (7.5%) Occasional (29-5%) HP:0002574
11 hypermagnesemia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002918
12 peptic ulcer 55 31 occasional (7.5%) Occasional (29-5%) HP:0004398
13 fatigue 55 31 occasional (7.5%) Occasional (29-5%) HP:0012378
14 hypomagnesiuria 55 31 occasional (7.5%) Occasional (29-5%) HP:0012609
15 nephrolithiasis 55 31 very rare (1%) Very rare (<4-1%) HP:0000787
16 pancreatitis 55 31 very rare (1%) Very rare (<4-1%) HP:0001733
17 hypocalcemic seizures 55 31 very rare (1%) Very rare (<4-1%) HP:0002199
18 autoimmunity 55 31 very rare (1%) Very rare (<4-1%) HP:0002960
19 lipoma 55 31 very rare (1%) Very rare (<4-1%) HP:0012032
20 hypercalcemia 55 Obligate (100%)
21 nephrocalcinosis 55 Excluded (0%)

Drugs & Therapeutics for Familial Hypocalciuric Hypercalcemia

Drugs for Familial Hypocalciuric Hypercalcemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Plasminogen Phase 2
2 Arginine Vasopressin
3 Calcium, Dietary
4 Liver Extracts

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal Cancer Recruiting NCT02960724 Phase 2
2 Serum Calcium to Phosphorous Ratio (Ca/P) as a Simple, Inexpensive Screening Tool in the Diagnosis of Primary Hyperparathyroidism Completed NCT03027349
3 Studies of Inherited Diseases of Metabolism Recruiting NCT00001345

Search NIH Clinical Center for Familial Hypocalciuric Hypercalcemia

Genetic Tests for Familial Hypocalciuric Hypercalcemia

Genetic tests related to Familial Hypocalciuric Hypercalcemia:

# Genetic test Affiliating Genes
1 Familial Hypocalciuric Hypercalcemia 28

Anatomical Context for Familial Hypocalciuric Hypercalcemia

MalaCards organs/tissues related to Familial Hypocalciuric Hypercalcemia:

38
Bone, Liver, Kidney

Publications for Familial Hypocalciuric Hypercalcemia

Articles related to Familial Hypocalciuric Hypercalcemia:

(show top 50) (show all 113)
# Title Authors Year
1
Familial Hypocalciuric Hypercalcemia as an Atypical Form of Primary Hyperparathyroidism. ( 29115694 )
2018
2
Familial hypocalciuric hypercalcemia type 1 due to a novel homozygous mutation of the calcium-sensing receptor gene. ( 28620806 )
2017
3
Utility of Cinacalcet in Familial Hypocalciuric Hypercalcemia. ( 28459040 )
2017
4
Familial Hypocalciuric Hypercalcemia (FHH) ( 29083672 )
2017
5
Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia. ( 28176280 )
2017
6
Cinacalcet Rectifies Hypercalcemia in a Patient With Familial Hypocalciuric Hypercalcemia Type 2 (FHH2) Caused by a Germline Loss-of-Function GI+11 Mutation. ( 28833550 )
2017
7
Calcimimetic Use in Familial Hypocalciuric Hypercalcemia - A Perspective in Endocrinology. ( 28945857 )
2017
8
AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia. ( 27913609 )
2017
9
Atypical skeletal manifestations of rickets in a familial hypocalciuric hypercalcemia patient. ( 28690912 )
2017
10
The Biochemical Profile of Familial Hypocalciuric Hypercalcemia and Primary Hyperparathyroidism during Pregnancy and Lactation: Two Case Reports and Review of the Literature. ( 27957351 )
2016
11
Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3. ( 27761240 )
2016
12
A novel mutation of the calcium-sensing receptor gene in a German subject with familial hypocalciuric hypercalcemia and primary hyperparathyroidism. ( 28222409 )
2016
13
Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences. ( 26963950 )
2016
14
G-Protein Subunit-I+11 Loss-of-Function Mutation, Thr54Met, Causing Familial Hypocalciuric Hypercalcemia Type 2 (FHH2). ( 26729423 )
2016
15
The cardiovascular system in familial hypocalciuric hypercalcemia: a cross-sectional study on physiological effects of inactivating variants in the calcium-sensing receptor gene. ( 27418061 )
2016
16
Identification and functional characterization of a CaSR mutation in an infant with Familial Hypocalciuric Hypercalcemia. ( 27087013 )
2016
17
Familial hypocalciuric hypercalcemia associated with crystal deposition disease. ( 25444087 )
2015
18
Familial hypocalciuric hypercalcemia with a de novo heterozygous mutation of calcium-sensing receptor. ( 26019872 )
2015
19
Letter to the editor: Distinguishing typical primary hyperparathyroidism from familial hypocalciuric hypercalcemia by using an index of urinary calcium. ( 25658165 )
2015
20
Identification and functional analysis of a novel CaSR mutation in a family with familial hypocalciuric hypercalcemia. ( 26386835 )
2015
21
Cinacalcet Treatment in an Adolescent With Concurrent 22q11.2 Deletion Syndrome and Familial Hypocalciuric Hypercalcemia Type 3 Caused by AP2S1 Mutation. ( 25993639 )
2015
22
Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations. ( 24731014 )
2014
23
Familial hypocalciuric hypercalcemia and calcium sensing receptor. ( 25163238 )
2014
24
Increased trabecular volumetric bone mass density in Familial Hypocalciuric Hypercalcemia (FHH) type 1: a cross-sectional study. ( 24894639 )
2014
25
Muscle function and quality of life are not impaired in familial hypocalciuric hypercalcemia: a cross-sectional study on physiological effects of inactivating variants in the calcium-sensing receptor gene (CASR). ( 23764372 )
2013
26
Familial hypocalciuric hypercalcemia: an atypical presentation. ( 22789152 )
2013
27
Differentiating familial hypocalciuric hypercalcemia from primary hyperparathyroidism. ( 23425644 )
2013
28
Diffuse idiopathic skeletal hyperostosis and familial hypocalciuric hypercalcemia: a unique association in a young female. ( 23531992 )
2013
29
Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. ( 23222959 )
2013
30
Ruling in a suspect: the role of AP2S1 mutations in familial hypocalciuric hypercalcemia type 3. ( 24311792 )
2013
31
Calcium signaling regulates trafficking of familial hypocalciuric hypercalcemia (FHH) mutants of the calcium sensing receptor. ( 23077345 )
2012
32
Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine. ( 21643651 )
2012
33
A novel germline inactivating mutation in the CASR gene in an Italian kindred affected by familial hypocalciuric hypercalcemia. ( 22315359 )
2012
34
A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia. ( 22620673 )
2012
35
Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications. ( 22232026 )
2012
36
Clinical and biochemical outcomes of cinacalcet treatment of familial hypocalciuric hypercalcemia: a case series. ( 22142470 )
2011
37
Benign familial hypocalciuric hypercalcemia. ( 21478088 )
2011
38
Forearm bone mineral density in familial hypocalciuric hypercalcemia and primary hyperparathyroidism: a comparative study. ( 21785908 )
2011
39
New mutation in the CASR gene in a family with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). ( 21468522 )
2011
40
Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia. ( 20495831 )
2010
41
Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia. ( 20697181 )
2010
42
Identification of a second kindred with familial hypocalciuric hypercalcemia type 3 (FHH3) narrows localization to a <3.5 megabase pair region on chromosome 19q13.3. ( 20133464 )
2010
43
A novel mutation in the calcium-sensing receptor gene in an Irish pedigree showing familial hypocalciuric hypercalcemia: a case report. ( 21034470 )
2010
44
Kabuki syndrome and Crohn disease in a child with familial hypocalciuric hypercalcemia. ( 21175100 )
2010
45
A novel loss-of-function mutation, Gln459Arg, of the calcium-sensing receptor gene associated with apparent autosomal recessive inheritance of familial hypocalciuric hypercalcemia. ( 19789209 )
2009
46
Familial hypocalciuric hypercalcemia revealed by chondrocalcinosis. ( 19467900 )
2009
47
Identification and functional characterization of loss-of-function mutations of the calcium-sensing receptor in four Italian kindreds with familial hypocalciuric hypercalcemia. ( 19073830 )
2009
48
A patient with primary hyperparathyroidism associated with familial hypocalciuric hypercalcemia induced by a novel germline CaSR gene mutation. ( 19423460 )
2009
49
Spontaneous rib fractures in a black woman with familial hypocalciuric hypercalcemia. ( 18830196 )
2008
50
Plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism. ( 18787045 )
2008

Variations for Familial Hypocalciuric Hypercalcemia

ClinVar genetic disease variations for Familial Hypocalciuric Hypercalcemia:

6 (show all 21)
# Gene Variation Type Significance SNP ID Assembly Location
1 CASR NM_000388.3(CASR): c.1058A> C (p.Glu353Ala) single nucleotide variant Likely pathogenic rs193922419 GRCh37 Chromosome 3, 121980940: 121980940
2 CASR NM_000388.3(CASR): c.1244G> A (p.Arg415Gln) single nucleotide variant Likely pathogenic rs193922421 GRCh37 Chromosome 3, 121981126: 121981126
3 CASR NM_000388.3(CASR): c.1512_1515delGTTT (p.Phe505Argfs) deletion Likely pathogenic rs193922422 GRCh37 Chromosome 3, 121994793: 121994796
4 CASR NM_000388.3(CASR): c.1525G> A (p.Gly509Arg) single nucleotide variant Pathogenic rs193922423 GRCh37 Chromosome 3, 121994806: 121994806
5 CASR NM_000388.3(CASR): c.166delG (p.Glu56Serfs) deletion Likely pathogenic rs193922424 GRCh37 Chromosome 3, 121973202: 121973202
6 CASR NM_000388.3(CASR): c.1676C> A (p.Pro559His) single nucleotide variant Likely pathogenic rs193922425 GRCh37 Chromosome 3, 122001027: 122001027
7 CASR NM_000388.3(CASR): c.1685G> C (p.Cys562Ser) single nucleotide variant Likely pathogenic rs193922426 GRCh37 Chromosome 3, 122001036: 122001036
8 CASR NM_000388.3(CASR): c.1685_1686delGCinsCT (p.Cys562Ser) indel Likely pathogenic rs193922427 GRCh37 Chromosome 3, 122001036: 122001037
9 CASR NM_000388.3(CASR): c.1884delC (p.Phe629Leufs) deletion Likely pathogenic rs193922429 GRCh37 Chromosome 3, 122002685: 122002685
10 CASR NM_000388.3(CASR): c.2014C> A (p.Pro672Thr) single nucleotide variant Likely pathogenic rs193922431 GRCh37 Chromosome 3, 122002815: 122002815
11 CASR NM_000388.3(CASR): c.2243C> A (p.Pro748His) single nucleotide variant Likely pathogenic rs193922433 GRCh38 Chromosome 3, 122284197: 122284197
12 CASR NM_000388.3(CASR): c.2254C> T (p.Arg752Cys) single nucleotide variant Likely pathogenic rs193922434 GRCh37 Chromosome 3, 122003055: 122003055
13 CASR NM_000388.3(CASR): c.2435T> C (p.Leu812Pro) single nucleotide variant Likely pathogenic rs193922435 GRCh37 Chromosome 3, 122003236: 122003236
14 CASR NM_000388.3(CASR): c.2489G> A (p.Gly830Asp) single nucleotide variant Likely pathogenic rs193922436 GRCh37 Chromosome 3, 122003290: 122003290
15 CASR NM_000388.3(CASR): c.2644A> T (p.Lys882Ter) single nucleotide variant Likely pathogenic rs193922437 GRCh37 Chromosome 3, 122003445: 122003445
16 CASR NM_000388.3(CASR): c.269A> C (p.Asn90Thr) single nucleotide variant Likely pathogenic rs193922439 GRCh37 Chromosome 3, 121976011: 121976011
17 CASR NM_000388.3(CASR): c.380A> G (p.Glu127Gly) single nucleotide variant Likely pathogenic rs121909260 GRCh37 Chromosome 3, 121976122: 121976122
18 CASR NM_000388.3(CASR): c.496A> G (p.Ser166Gly) single nucleotide variant Likely pathogenic rs193922441 GRCh37 Chromosome 3, 121980378: 121980378
19 CASR NM_000388.3(CASR): c.554delG (p.Arg185Glnfs) deletion Likely pathogenic rs193922442 GRCh37 Chromosome 3, 121980436: 121980436
20 CASR NM_000388.3(CASR): c.643G> C (p.Asp215His) single nucleotide variant Likely pathogenic rs193922443 GRCh37 Chromosome 3, 121980525: 121980525
21 CASR NM_000388.3(CASR): c.974G> A (p.Gly325Glu) single nucleotide variant Likely pathogenic rs193922444 GRCh37 Chromosome 3, 121980856: 121980856

Expression for Familial Hypocalciuric Hypercalcemia

Search GEO for disease gene expression data for Familial Hypocalciuric Hypercalcemia.

Pathways for Familial Hypocalciuric Hypercalcemia

Pathways related to Familial Hypocalciuric Hypercalcemia according to KEGG:

36
# Name Kegg Source Accession
1 Calcium signaling pathway hsa04020
2 Endocrine and other factor-regulated calcium reabsorption hsa04961

GO Terms for Familial Hypocalciuric Hypercalcemia

Cellular components related to Familial Hypocalciuric Hypercalcemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 clathrin-coated pit GO:0005905 8.62 AP2S1 FNBP1

Biological processes related to Familial Hypocalciuric Hypercalcemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.5 ARHGAP4 SRGAP1 SRGAP2
2 positive regulation of signal transduction GO:0009967 9.26 ARHGAP4 PTH
3 Rho protein signal transduction GO:0007266 9.16 ARHGAP4 PTH
4 regulation of small GTPase mediated signal transduction GO:0051056 9.13 ARHGAP4 SRGAP1 SRGAP2
5 response to fibroblast growth factor GO:0071774 8.62 CASR PTH

Molecular functions related to Familial Hypocalciuric Hypercalcemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 GTPase activator activity GO:0005096 9.13 ARHGAP4 SRGAP1 SRGAP2
2 Rac GTPase binding GO:0048365 8.8 ARHGAP4 SRGAP1 SRGAP2

Sources for Familial Hypocalciuric Hypercalcemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....