MCID: HYP608
MIFTS: 43

Hypocalciuric Hypercalcemia, Familial, Type Iii

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

Aliases & Classifications for Hypocalciuric Hypercalcemia, Familial, Type Iii

MalaCards integrated aliases for Hypocalciuric Hypercalcemia, Familial, Type Iii:

Name: Hypocalciuric Hypercalcemia, Familial, Type Iii 57 29 13 6 73
Hhc3 57 12 53 75
Familial Hypocalciuric Hypercalcemia Type 3 12 53 59
Fbh3 57 53 75
Hypercalcemia, Familial Benign, Oklahoma Type 57 53
Hypocalciuric Hypercalcemia, Familial, Type 3 53 40
Familial Hypocalciuric Hypercalcemia 3 12 15
Hypocalciuric Hypercalcemia Type Iii 12 75
Fhh Type 3 12 59
Familial Benign Hypercalcemia, Oklahoma Variant 53
Familial Benign Hypercalcemia, Type Iii; Fbh3 57
Familial Benign Hypocalciuric Hypercalcemia 3 75
Familial Benign Hypercalcemia Oklahoma Type 75
Hypercalcemia, Familial Benign, Type Iii 57
Familial Benign Hypercalcemia, Type Iii 57
Hypocalciuric Hypercalcemia, Familial 3 75
Hypercalcemia, Familial Benign, Type 3 53
Hypocalciuric Hypercalcemia, Type Iii 57
Familial Benign Hypercalcemia, Type 3 53
Familial Benign Hypercalcemia 3 75
Fbhok 53
Fbhh3 75
Fhh3 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable skeletal features may be present
hypercalcemia appears as early as 1.5 years of age
serum pth increases with age and is above the normal range by age 30 years


HPO:

32
hypocalciuric hypercalcemia, familial, type iii:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 600740
Disease Ontology 12 DOID:0060702
ICD10 33 E83.5
Orphanet 59 ORPHA101050
MESH via Orphanet 45 C537147
ICD10 via Orphanet 34 E83.5
UMLS via Orphanet 74 C1833372
MedGen 42 C1833372
MeSH 44 D006934
UMLS 73 C1833372

Summaries for Hypocalciuric Hypercalcemia, Familial, Type Iii

NIH Rare Diseases : 53 Familial hypocalciuric hypercalcemia (FHH) type 3 is one of three recognized types of FHH, an inherited condition that causes abnormally high levels of calcium in the blood (hypercalcemia). FHH also causes high levels of parathyroid hormone (PTH) and low levels of calcium in the urine (hypocalciuria). In most cases, FHH does not cause signs or symptoms. However, some people with FHH do report symptoms. Signs and symptoms that may occur in some people with FHH type 3 include high magnesium in addition to calcium, general symptoms of hypercalcemia (such as weakness, fatigue, muscle pain, constipation, depression, confusion, and excessive thirst), lower bone mineral density, behavioral disorders, and learning disabilities. FHH type 3 is caused by a mutation in the AP2S1 gene and inheritance is autosomal dominant. Treatment is generally not necessary in people with no signs or symptoms of FHH. In severe cases however, removal of the parathyroid gland (parathyroidectomy) may be recommended.

MalaCards based summary : Hypocalciuric Hypercalcemia, Familial, Type Iii, also known as hhc3, is related to familial hypocalciuric hypercalcemia and pseudopseudohypoparathyroidism, and has symptoms including bone pain An important gene associated with Hypocalciuric Hypercalcemia, Familial, Type Iii is AP2S1 (Adaptor Related Protein Complex 2 Subunit Sigma 1), and among its related pathways/superpathways are Ca, cAMP and Lipid Signaling and Endochondral Ossification. Affiliated tissues include bone, and related phenotypes are renal insufficiency and depressivity

UniProtKB/Swiss-Prot : 75 Hypocalciuric hypercalcemia, familial 3: A form of hypocalciuric hypercalcemia, a disorder of mineral homeostasis that is transmitted as an autosomal dominant trait with a high degree of penetrance. It is characterized biochemically by lifelong elevation of serum calcium concentrations and is associated with inappropriately low urinary calcium excretion and a normal or mildly elevated circulating parathyroid hormone level. Hypermagnesemia is typically present. Affected individuals are usually asymptomatic and the disorder is considered benign. However, chondrocalcinosis and pancreatitis occur in some adults.

Disease Ontology : 12 A familial hypocalciuric hypercalcemia that has material basis in heterozygous mutation in the AP2S1 gene on chromosome 19q13.

Description from OMIM: 600740

Related Diseases for Hypocalciuric Hypercalcemia, Familial, Type Iii

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 Hypocalciuric Hypercalcemia, Familial, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 familial hypocalciuric hypercalcemia 29.3 AP2S1 CASR GNA11 PTH
2 pseudopseudohypoparathyroidism 10.2 GNA11 PTH
3 hypocalcemia, autosomal dominant 1 10.1 CASR GNA11
4 hypoparathyroidism, familial isolated 10.1 CASR PTH
5 calciphylaxis 10.1 CASR PTH
6 osteitis fibrosa 10.1 CASR PTH
7 phosphorus metabolism disease 10.1 CASR PTH
8 secondary hyperparathyroidism of renal origin 10.0 CASR PTH
9 neuroendocrine tumor 10.0
10 multiple endocrine neoplasia 10.0
11 renal osteodystrophy 10.0 CASR PTH
12 parathyroid carcinoma 10.0 CASR PTH
13 hyperphosphatemia 9.9 CASR PTH
14 extraskeletal chondroma 9.8 PTH PTHLH
15 sclerosing hepatic carcinoma 9.8 PTH PTHLH
16 hypocalciuric hypercalcemia, familial, type i 9.8 AP2S1 CASR GNA11
17 invasive malignant thymoma 9.8 PTH PTHLH
18 uremia 9.8 CASR PTH
19 chondrocalcinosis 9.8 AP2S1 CASR GNA11
20 clear cell adenoma 9.8 PTH PTHLH
21 oncogenic osteomalacia 9.7 PTH PTHLH
22 jaw cancer 9.7 PTH PTHLH
23 pseudohypoparathyroidism, type ib 9.7 PTH PTHLH
24 cloacogenic carcinoma 9.7 PTH PTHLH
25 metaphyseal chondrodysplasia, jansen type 9.6 PTH PTHLH
26 multiple endocrine neoplasia, type i 9.6 CASR PTH
27 pseudohypoparathyroidism 9.6 PTH PTHLH
28 osteomalacia 9.5 CASR PTHLH
29 chronic kidney failure 9.3 CASR PTH
30 acquired metabolic disease 9.3 PTH PTHLH
31 hypercalcemia, infantile, 1 9.2 CASR PTH PTHLH
32 parathyroid gland disease 9.2 CASR PTH PTHLH
33 mineral metabolism disease 9.2 CASR PTH PTHLH
34 parathyroid adenoma 9.2 CASR PTH PTHLH
35 hypoparathyroidism 9.2 CASR PTH PTHLH
36 primary hyperparathyroidism 9.2 CASR PTH PTHLH
37 hyperparathyroidism 9.2 CASR PTH PTHLH
38 hypocalciuric hypercalcemia, familial, type ii 9.2 AP2S1 CASR GNA11 PTH
39 bone disease 9.2 CASR PTH PTHLH
40 osteoporosis 8.9 CASR PTH PTHLH

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



Diseases related to Hypocalciuric Hypercalcemia, Familial, Type Iii

Symptoms & Phenotypes for Hypocalciuric Hypercalcemia, Familial, Type Iii

Symptoms via clinical synopsis from OMIM:

57
Skeletal:
osteomalacia
bone pain
chondrocalcinosis
pseudofracture

Genitourinary Kidneys:
renal failure (rare)
medullary cystic disease (rare)

Neurologic Central Nervous System:
headaches (in some patients)

Endocrine Features:
elevated serum parathyroid hormone (pth) levels
parathyroid gland unremarkable on ultrasound
parathyroid tissue unremarkable on biopsy

Laboratory Abnormalities:
hypercalcemia
hypocalciuria
hypophosphatemia, mild
hypermagnesemia, mild

Muscle Soft Tissue:
muscle weakness (in some patients)
periarticular calcifications (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
depression (in some patients)
fatigue (in some patients)


Clinical features from OMIM:

600740

Human phenotypes related to Hypocalciuric Hypercalcemia, Familial, Type Iii:

32 (show all 19)
# Description HPO Frequency HPO Source Accession
1 renal insufficiency 32 occasional (7.5%) HP:0000083
2 depressivity 32 occasional (7.5%) HP:0000716
3 nephrolithiasis 32 occasional (7.5%) HP:0000787
4 chondrocalcinosis 32 HP:0000934
5 multiple lipomas 32 HP:0001012
6 muscle weakness 32 occasional (7.5%) HP:0001324
7 pancreatitis 32 HP:0001733
8 hypophosphatemia 32 HP:0002148
9 headache 32 occasional (7.5%) HP:0002315
10 bone pain 32 HP:0002653
11 osteomalacia 32 HP:0002749
12 hypermagnesemia 32 HP:0002918
13 hypercalcemia 32 HP:0003072
14 hypocalciuria 32 HP:0003127
15 parathormone-independent increased renal tubular calcium reabsorption 32 HP:0003529
16 peptic ulcer 32 occasional (7.5%) HP:0004398
17 primary hyperparathyroidism 32 HP:0008200
18 multiple small medullary renal cysts 32 occasional (7.5%) HP:0008659
19 fatigue 32 occasional (7.5%) HP:0012378

UMLS symptoms related to Hypocalciuric Hypercalcemia, Familial, Type Iii:


bone pain

MGI Mouse Phenotypes related to Hypocalciuric Hypercalcemia, Familial, Type Iii:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.65 PTH PTHLH CASR FANCD2 GNA11
2 hematopoietic system MP:0005397 9.55 CASR FANCD2 GNA11 PTH PTHLH
3 immune system MP:0005387 9.35 CASR FANCD2 GNA11 PTH PTHLH
4 limbs/digits/tail MP:0005371 8.92 FANCD2 GNA11 PTH PTHLH

Drugs & Therapeutics for Hypocalciuric Hypercalcemia, Familial, Type Iii

Search Clinical Trials , NIH Clinical Center for Hypocalciuric Hypercalcemia, Familial, Type Iii

Genetic Tests for Hypocalciuric Hypercalcemia, Familial, Type Iii

Genetic tests related to Hypocalciuric Hypercalcemia, Familial, Type Iii:

# Genetic test Affiliating Genes
1 Hypocalciuric Hypercalcemia, Familial, Type Iii 29 AP2S1

Anatomical Context for Hypocalciuric Hypercalcemia, Familial, Type Iii

MalaCards organs/tissues related to Hypocalciuric Hypercalcemia, Familial, Type Iii:

41
Bone

Publications for Hypocalciuric Hypercalcemia, Familial, Type Iii

Articles related to Hypocalciuric Hypercalcemia, Familial, Type Iii:

# Title Authors Year
1
Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3. ( 27761240 )
2016
2
Cinacalcet Treatment in an Adolescent With Concurrent 22q11.2 Deletion Syndrome and Familial Hypocalciuric Hypercalcemia Type 3 Caused by AP2S1 Mutation. ( 25993639 )
2015
3
Mutations in AP2S1 cause familial hypocalciuric hypercalcemia type 3. ( 23222959 )
2013
4
Ruling in a suspect: the role of AP2S1 mutations in familial hypocalciuric hypercalcemia type 3. ( 24311792 )
2013
5
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

Variations for Hypocalciuric Hypercalcemia, Familial, Type Iii

UniProtKB/Swiss-Prot genetic disease variations for Hypocalciuric Hypercalcemia, Familial, Type Iii:

75
# Symbol AA change Variation ID SNP ID
1 AP2S1 p.Arg15Cys VAR_069570 rs397514498
2 AP2S1 p.Arg15His VAR_069571 rs397514499
3 AP2S1 p.Arg15Leu VAR_069572 rs397514499

ClinVar genetic disease variations for Hypocalciuric Hypercalcemia, Familial, Type Iii:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 AP2S1 NM_004069.4(AP2S1): c.43C> T (p.Arg15Cys) single nucleotide variant Pathogenic rs397514498 GRCh37 Chromosome 19, 47349360: 47349360
2 AP2S1 NM_004069.4(AP2S1): c.43C> T (p.Arg15Cys) single nucleotide variant Pathogenic rs397514498 GRCh38 Chromosome 19, 46846103: 46846103
3 AP2S1 NM_004069.4(AP2S1): c.44G> T (p.Arg15Leu) single nucleotide variant Pathogenic rs397514499 GRCh37 Chromosome 19, 47349359: 47349359
4 AP2S1 NM_004069.4(AP2S1): c.44G> T (p.Arg15Leu) single nucleotide variant Pathogenic rs397514499 GRCh38 Chromosome 19, 46846102: 46846102
5 AP2S1 NM_004069.4(AP2S1): c.44G> A (p.Arg15His) single nucleotide variant Pathogenic rs397514499 GRCh37 Chromosome 19, 47349359: 47349359
6 AP2S1 NM_004069.4(AP2S1): c.44G> A (p.Arg15His) single nucleotide variant Pathogenic rs397514499 GRCh38 Chromosome 19, 46846102: 46846102

Expression for Hypocalciuric Hypercalcemia, Familial, Type Iii

Search GEO for disease gene expression data for Hypocalciuric Hypercalcemia, Familial, Type Iii.

Pathways for Hypocalciuric Hypercalcemia, Familial, Type Iii

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

# Super pathways Score Top Affiliating Genes
1 11.36 CASR GNA11
2 10.97 PTH PTHLH
3 10.95 CASR GNA11 PTH PTHLH
4 10.72 GNA11 PTH PTHLH

GO Terms for Hypocalciuric Hypercalcemia, Familial, Type Iii

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

# Name GO ID Score Top Affiliating Genes
1 G-protein coupled receptor signaling pathway GO:0007186 9.67 CASR GNA11 PTH PTHLH
2 cellular calcium ion homeostasis GO:0006874 9.43 CASR PTH
3 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007189 9.4 PTH PTHLH
4 skeletal system development GO:0001501 9.33 GNA11 PTH PTHLH
5 negative regulation of chondrocyte differentiation GO:0032331 9.32 PTH PTHLH
6 obsolete positive regulation of cAMP biosynthetic process GO:0030819 9.26 PTH PTHLH
7 response to fibroblast growth factor GO:0071774 8.96 CASR PTH
8 cAMP metabolic process GO:0046058 8.62 PTH PTHLH

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

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.96 PTH PTHLH
2 peptide hormone receptor binding GO:0051428 8.62 PTH PTHLH

Sources for Hypocalciuric Hypercalcemia, Familial, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....