FBH
MCID: FML068
MIFTS: 46

Familial Hypocalciuric Hypercalcemia (FBH) malady

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

Aliases & Classifications for Familial Hypocalciuric Hypercalcemia

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Sources:
11Disease Ontology, 13DISEASES, 27GTR, 30ICD10, 31ICD10 via Orphanet, 48NIH Rare Diseases, 50Novoseek, 54Orphanet, 68UMLS
See all MalaCards sources

Aliases & Descriptions for Familial Hypocalciuric Hypercalcemia:

Name: Familial Hypocalciuric Hypercalcemia 11 48 54 27 13
Familial Benign Hypercalcemia 11 48 54 68
Fbhh 11 48 54
Fbh 11 48 54
 
Fhh 11 48 54
Familial Benign Hypocalciuric Hypercalcemia 11 54
Hypocalciuric Hypercalcemia, Familial, Type 1 68
Hypercalcemia, Familial Benign 50

Characteristics:

Orphanet epidemiological data:

54
familial hypocalciuric hypercalcemia:
Inheritance: Autosomal dominant; Age of onset: All ages; Age of death: normal life expectancy

Classifications:



External Ids:

Disease Ontology11 DOID:0060699
ICD1030 E83.5
Orphanet54 ORPHA405
ICD10 via Orphanet31 E83.5

Summaries for Familial Hypocalciuric Hypercalcemia

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NIH Rare Diseases:48 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, type i and hypocalciuric hypercalcemia, familial, type iii, and has symptoms including Array, Array and Array. An important gene associated with Familial Hypocalciuric Hypercalcemia is CASR (Calcium Sensing Receptor), and among its related pathways are Development_Hedgehog and PTH signaling pathways in bone and cartilage development and Signaling by Slit. Affiliated tissues include bone, breast and kidney.

Disease Ontology:11 A hypercalcemia characterized byautosomal dominant inheritance with elevation of serum calcium levels and decreased urinary calcium excretion.

Wikipedia:71 Familial hypocalciuric hypercalcemia (FHH) is a condition that can cause hypercalcemia, a serum calcium... more...

Related Diseases for Familial Hypocalciuric Hypercalcemia

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Diseases in the Familial Hypocalciuric Hypercalcemia family:

Hypocalciuric Hypercalcemia, Type I Hypocalciuric Hypercalcemia, 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 45)
idRelated DiseaseScoreTop Affiliating Genes
1hypocalciuric hypercalcemia, type i12.0
2hypocalciuric hypercalcemia, familial, type iii12.0
3hypocalciuric hypercalcemia, type ii11.9
4hyperparathyroidism10.6
5epilepsy idiopathic generalized 810.2CASR, CXADR
6striatonigral degeneration10.2CASR, PTH
7deafness, autosomal recessive 4210.2CASR, GNA11
8mesenchymal cell neoplasm10.2CASR, PTH
9waardenburg syndrome, type 4b10.2CASR, PTH
10listeria meningitis10.2CASR, GNA11
11pseudohypoparathyroidism ic10.1GNA11, PTH
12gastric antral vascular ectasia10.1CASR, PTH
13pseudohypoparathyroidism, type ib10.1GNA11, PTH
14pes anserinus tendinitis or bursitis10.1CASR, PTH
15hyperparathyroidism, familial primary10.1CASR, CDC73
16hypocalcemia, autosomal dominant10.1AP2S1, CASR, GNA11
17cerebrooculofacioskeletal syndrome 410.1AP2S1, CASR, GNA11
18inflammatory bowel disease 610.1AP2S1, CASR, GNA11
19tinea unguium10.1CASR, PTH
20weill-marchesani syndrome10.1CASR, PTH
21indian tick typhus10.1CASR, PTH
22prediabetes syndrome10.1ARHGAP4, PTH
23parathyroid gland disease10.1CASR, PTH, SPG7
24multiple endocrine neoplasia10.0
25central hypoventilation syndrome, congenital10.0CDC73, PTH
26epidermolysis bullosa, junctional, herlitz type10.0CASR, CDC73, PTH
27cowper gland carcinoma10.0CASR, CDC73, PTH
28opioid abuse10.0CASR, CDC73, PTH
29parathyroid carcinoma10.0CASR, CDC73, PTH
30leukemia, acute promyelocytic, somatic10.0CASR, CDC73, PTH
31subserous uterine fibroid10.0CASR, CDC73, PTH
32pre-eclampsia9.9CASR, PTH
33immune system organ benign neoplasm9.9CDC73, PTH
34breast cancer9.9
35alkaptonuria9.9
36insulinoma9.9
37hypoparathyroidism9.9
38chondrocalcinosis9.9
39neuroendocrine tumor9.9
40hyperostosis9.9
41adenoma9.9
42diffuse idiopathic skeletal hyperostosis9.9
43parathyroid adenoma9.9
44metastatic insulinoma9.9
45familial chronic myelocytic leukemia-like syndrome8.7AP2S1, ARHGAP4, CASR, CDC73, CXADR, FNBP1

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



Diseases related to familial hypocalciuric hypercalcemia

Symptoms & Phenotypes for Familial Hypocalciuric Hypercalcemia

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Human phenotypes related to Familial Hypocalciuric Hypercalcemia:

 54 64 (show all 21)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypercalcemia54 Obligate (100%)
2 hypocalciuria64 54 Obligate (100%) HP:0003127
3 reduced ratio of renal calcium clearance to creatinine clearance64 54 Very frequent (99-80%) HP:0003513
4 parathormone-independent increased renal tubular calcium reabsorption64 54 Very frequent (99-80%) HP:0003529
5 osteomalacia64 54 Frequent (79-30%) HP:0002749
6 infantile hypercalcemia64 54 Frequent (79-30%) HP:0008250
7 renal hypophosphatemia64 54 Frequent (79-30%) HP:0008732
8 chondrocalcinosis64 54 Occasional (29-5%) HP:0000934
9 nausea and vomiting64 54 Occasional (29-5%) HP:0002017
10 headache64 54 Occasional (29-5%) HP:0002315
11 episodic abdominal pain64 54 Occasional (29-5%) HP:0002574
12 hypermagnesemia64 54 Occasional (29-5%) HP:0002918
13 peptic ulcer64 54 Occasional (29-5%) HP:0004398
14 fatigue64 54 Occasional (29-5%) HP:0012378
15 hypomagnesiuria64 54 Occasional (29-5%) HP:0012609
16 nephrolithiasis64 54 Very rare (<4-1%) HP:0000787
17 pancreatitis64 54 Very rare (<4-1%) HP:0001733
18 hypocalcemic seizures64 54 Very rare (<4-1%) HP:0002199
19 autoimmunity64 54 Very rare (<4-1%) HP:0002960
20 lipoma64 54 Very rare (<4-1%) HP:0012032
21 nephrocalcinosis54 Excluded (0%)

Drugs & Therapeutics for Familial Hypocalciuric Hypercalcemia

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

(show all 9)
idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1PlasminogenPhase 2242
2
Teriparatideapproved, investigational13752232-67-416133850
Synonyms:
52232-67-4
D06078
Forteo
Forteo (TN)
 
TERIPARATIDE
Teriparatide (USAN/INN)
Teriparatide (genetical recombination)
Teriparatide (genetical recombination) (JAN)
Teriparatide recombinant human
3Liver Extracts4067
4Arginine Vasopressin299
5Calcium, Dietary5713
6vitamin d1724
7Vitamins5282
8Bone Density Conservation Agents3376
9glucocorticoids5103

Interventional clinical trials:

idNameStatusNCT IDPhase
1uPAR PET/CT for Staging Advanced and Localised Oral and Oropharyngeal CancerRecruitingNCT02960724Phase 2
2Serum Calcium to Phosphorous Ratio (Ca/P) as a Simple, Inexpensive Screening Tool in the Diagnosis of Primary HyperparathyroidismCompletedNCT03027349
3Studies of Inherited Diseases of MetabolismRecruitingNCT00001345
4Study of the Diagnostic Value of Stable Calcium Isotope Profiling in Bone and Calcium DisordersRecruitingNCT02252679

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Genetic Tests for Familial Hypocalciuric Hypercalcemia

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Genetic tests related to Familial Hypocalciuric Hypercalcemia:

id Genetic test Affiliating Genes
1 Familial Hypocalciuric Hypercalcemia27

Anatomical Context for Familial Hypocalciuric Hypercalcemia

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MalaCards organs/tissues related to Familial Hypocalciuric Hypercalcemia:

36
Bone, Breast, Kidney

Publications for Familial Hypocalciuric Hypercalcemia

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Articles related to Familial Hypocalciuric Hypercalcemia:

(show top 50)    (show all 106)
idTitleAuthorsYear
1
Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia. (28176280)
2017
2
AP2S1 and GNA11 mutations - not a common cause of familial hypocalciuric hypercalcemia. (27913609)
2017
3
Utility of Cinacalcet in Familial Hypocalciuric Hypercalcemia. (28459040)
2017
4
G-Protein Subunit-I+11 Loss-of-Function Mutation, Thr54Met, Causing Familial Hypocalciuric Hypercalcemia Type 2 (FHH2). (26729423)
2016
5
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
6
Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3. (27761240)
2016
7
Familial Hypocalciuric Hypercalcemia Types 1 and 3 and Primary Hyperparathyroidism: Similarities and Differences. (26963950)
2016
8
A novel mutation of the calcium-sensing receptor gene in a German subject with familial hypocalciuric hypercalcemia and primary hyperparathyroidism. (28222409)
2016
9
The Biochemical Profile of Familial Hypocalciuric Hypercalcemia and Primary Hyperparathyroidism during Pregnancy and Lactation: Two Case Reports and Review of the Literature. (27957351)
2016
10
Identification and functional characterization of a CaSR mutation in an infant with Familial Hypocalciuric Hypercalcemia. (27087013)
2016
11
Familial hypocalciuric hypercalcemia with a de novo heterozygous mutation of calcium-sensing receptor. (26019872)
2015
12
Cinacalcet Treatment in an Adolescent With Concurrent 22q11.2 Deletion Syndrome and Familial Hypocalciuric Hypercalcemia Type 3 Caused by AP2S1 Mutation. (25993639)
2015
13
Familial hypocalciuric hypercalcemia associated with crystal deposition disease. (25444087)
2015
14
Identification and functional analysis of a novel CaSR mutation in a family with familial hypocalciuric hypercalcemia. (26386835)
2015
15
Letter to the editor: Distinguishing typical primary hyperparathyroidism from familial hypocalciuric hypercalcemia by using an index of urinary calcium. (25658165)
2015
16
Increased trabecular volumetric bone mass density in Familial Hypocalciuric Hypercalcemia (FHH) type 1: a cross-sectional study. (24894639)
2014
17
Codon Arg15 mutations of the AP2S1 gene: common occurrence in familial hypocalciuric hypercalcemia cases negative for calcium-sensing receptor (CASR) mutations. (24731014)
2014
18
Familial hypocalciuric hypercalcemia and calcium sensing receptor. (25163238)
2014
19
Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. (23222959)
2013
20
Diffuse idiopathic skeletal hyperostosis and familial hypocalciuric hypercalcemia: a unique association in a young female. (23531992)
2013
21
Differentiating familial hypocalciuric hypercalcemia from primary hyperparathyroidism. (23425644)
2013
22
Ruling in a suspect: the role of AP2S1 mutations in familial hypocalciuric hypercalcemia type 3. (24311792)
2013
23
Familial hypocalciuric hypercalcemia: an atypical presentation. (22789152)
2013
24
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
25
Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications. (22232026)
2012
26
A novel CaSR mutation presenting as a severe case of neonatal familial hypocalciuric hypercalcemia. (22620673)
2012
27
A novel germline inactivating mutation in the CASR gene in an Italian kindred affected by familial hypocalciuric hypercalcemia. (22315359)
2012
28
Familial hypocalciuric hypercalcemia: new mutation in the CASR gene converting valine 697 to methionine. (21643651)
2012
29
Calcium signaling regulates trafficking of familial hypocalciuric hypercalcemia (FHH) mutants of the calcium sensing receptor. (23077345)
2012
30
Benign familial hypocalciuric hypercalcemia. (21478088)
2011
31
Clinical and biochemical outcomes of cinacalcet treatment of familial hypocalciuric hypercalcemia: a case series. (22142470)
2011
32
Forearm bone mineral density in familial hypocalciuric hypercalcemia and primary hyperparathyroidism: a comparative study. (21785908)
2011
33
New mutation in the CASR gene in a family with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT). (21468522)
2011
34
Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia. (20495831)
2010
35
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
36
Kabuki syndrome and Crohn disease in a child with familial hypocalciuric hypercalcemia. (21175100)
2010
37
Identification and functional analysis of novel calcium-sensing receptor gene mutation in familial hypocalciuric hypercalcemia. (20697181)
2010
38
A novel mutation in the calcium-sensing receptor gene in an Irish pedigree showing familial hypocalciuric hypercalcemia: a case report. (21034470)
2010
39
A patient with primary hyperparathyroidism associated with familial hypocalciuric hypercalcemia induced by a novel germline CaSR gene mutation. (19423460)
2009
40
Identification and functional characterization of loss-of-function mutations of the calcium-sensing receptor in four Italian kindreds with familial hypocalciuric hypercalcemia. (19073830)
2009
41
Familial hypocalciuric hypercalcemia revealed by chondrocalcinosis. (19467900)
2009
42
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
43
Insulinoma cell calcium-sensing receptor influences insulin secretion in a case with concurrent familial hypocalciuric hypercalcemia and malignant metastatic insulinoma. (18430790)
2008
44
Plasma 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and parathyroid hormone in familial hypocalciuric hypercalcemia and primary hyperparathyroidism. (18787045)
2008
45
Familial hypocalciuric hypercalcemia: review of three cases. (22964128)
2008
46
Spontaneous rib fractures in a black woman with familial hypocalciuric hypercalcemia. (18830196)
2008
47
Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population. (17698911)
2007
48
Familial hypocalciuric hypercalcemia in the donor and recipient of a living related donor kidney transplant. (17217434)
2007
49
Identification and functional characterization of a novel mutation in the calcium-sensing receptor gene in familial hypocalciuric hypercalcemia: modulation of clinical severity by vitamin D status. (17473068)
2007
50
Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia. (15879434)
2005

Variations for Familial Hypocalciuric Hypercalcemia

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Clinvar genetic disease variations for Familial Hypocalciuric Hypercalcemia:

5 (show all 22)
id Gene Variation Type Significance SNP ID Assembly Location
1CASRNM_ 000388.3(CASR): c.1058A> C (p.Glu353Ala)SNVLikely pathogenicrs193922419GRCh37Chr 3, 121980940: 121980940
2CASRNM_ 000388.3(CASR): c.1244G> A (p.Arg415Gln)SNVLikely pathogenicrs193922421GRCh37Chr 3, 121981126: 121981126
3CASRNM_ 000388.3(CASR): c.1512_ 1515delGTTT (p.Phe505Argfs)deletionLikely pathogenicrs193922422GRCh37Chr 3, 121994793: 121994796
4CASRNM_ 000388.3(CASR): c.1525G> A (p.Gly509Arg)SNVPathogenicrs193922423GRCh37Chr 3, 121994806: 121994806
5CASRNM_ 000388.3(CASR): c.166delG (p.Glu56Serfs)deletionLikely pathogenicrs193922424GRCh37Chr 3, 121973202: 121973202
6CASRNM_ 000388.3(CASR): c.1676C> A (p.Pro559His)SNVLikely pathogenicrs193922425GRCh37Chr 3, 122001027: 122001027
7CASRNM_ 000388.3(CASR): c.1685G> C (p.Cys562Ser)SNVLikely pathogenicrs193922426GRCh37Chr 3, 122001036: 122001036
8CASRNM_ 000388.3(CASR): c.1685_ 1686delGCinsCT (p.Cys562Ser)indelLikely pathogenicrs193922427GRCh37Chr 3, 122001036: 122001037
9CASRNM_ 000388.3(CASR): c.1884delC (p.Phe629Leufs)deletionLikely pathogenicrs193922429GRCh37Chr 3, 122002685: 122002685
10CASRNM_ 000388.3(CASR): c.2014C> A (p.Pro672Thr)SNVLikely pathogenicrs193922431GRCh37Chr 3, 122002815: 122002815
11CASRNM_ 000388.3(CASR): c.2243C> A (p.Pro748His)SNVLikely pathogenicrs193922433GRCh38Chr 3, 122284197: 122284197
12CASRNM_ 000388.3(CASR): c.2254C> T (p.Arg752Cys)SNVLikely pathogenicrs193922434GRCh37Chr 3, 122003055: 122003055
13CASRNM_ 000388.3(CASR): c.2435T> C (p.Leu812Pro)SNVLikely pathogenicrs193922435GRCh37Chr 3, 122003236: 122003236
14CASRNM_ 000388.3(CASR): c.2489G> A (p.Gly830Asp)SNVLikely pathogenicrs193922436GRCh37Chr 3, 122003290: 122003290
15CASRNM_ 000388.3(CASR): c.2644A> T (p.Lys882Ter)SNVLikely pathogenicrs193922437GRCh37Chr 3, 122003445: 122003445
16CASRNM_ 000388.3(CASR): c.269A> C (p.Asn90Thr)SNVLikely pathogenicrs193922439GRCh37Chr 3, 121976011: 121976011
17CASRNM_ 000388.3(CASR): c.3091G> A (p.Gly1031Ser)SNVLikely pathogenicrs142704083GRCh37Chr 3, 122003892: 122003892
18CASRNM_ 000388.3(CASR): c.380A> G (p.Glu127Gly)SNVLikely pathogenicrs121909260GRCh37Chr 3, 121976122: 121976122
19CASRNM_ 000388.3(CASR): c.496A> G (p.Ser166Gly)SNVLikely pathogenicrs193922441GRCh37Chr 3, 121980378: 121980378
20CASRNM_ 000388.3(CASR): c.554delG (p.Arg185Glnfs)deletionLikely pathogenicrs193922442GRCh37Chr 3, 121980436: 121980436
21CASRNM_ 000388.3(CASR): c.643G> C (p.Asp215His)SNVLikely pathogenicrs193922443GRCh37Chr 3, 121980525: 121980525
22CASRNM_ 000388.3(CASR): c.974G> A (p.Gly325Glu)SNVLikely pathogenicrs193922444GRCh37Chr 3, 121980856: 121980856

Expression for genes affiliated with Familial Hypocalciuric Hypercalcemia

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

Pathways for genes affiliated with Familial Hypocalciuric Hypercalcemia

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Pathways related to Familial Hypocalciuric Hypercalcemia according to GeneCards Suite gene sharing:

idSuper pathwaysScoreTop Affiliating Genes
19.6GNA11, PTH
29.3GNA11, SRGAP1
39.1ARHGAP4, SRGAP1

GO Terms for genes affiliated with Familial Hypocalciuric Hypercalcemia

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

idNameGO IDScoreTop Affiliating Genes
1clathrin-coated pitGO:00059059.6AP2S1, FNBP1

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

idNameGO IDScoreTop Affiliating Genes
1response to fibroblast growth factorGO:007177410.2CASR, PTH
2positive regulation of signal transductionGO:000996710.0ARHGAP4, PTH
3Rho protein signal transductionGO:00072669.5ARHGAP4, PTH

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

idNameGO IDScoreTop Affiliating Genes
1Rac GTPase bindingGO:00483659.1ARHGAP4, SRGAP1

Sources for Familial Hypocalciuric Hypercalcemia

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet