MCID: HYP726
MIFTS: 47

Hypercalcemia, Infantile, 1

Categories: Genetic diseases, Nephrological diseases, Endocrine diseases, Rare diseases

Aliases & Classifications for Hypercalcemia, Infantile, 1

MalaCards integrated aliases for Hypercalcemia, Infantile, 1:

Name: Hypercalcemia, Infantile, 1 54 71
Idiopathic Hypercalcemia of Infancy 71 29
Hypercalcemia 42 69
Hypercalcemia Infantile 71
Hcinf1 71

Characteristics:

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
most patients develop symptoms while on prophylactic vitamin d supplementation in infancy
some patients may not present until adulthood


HPO:

32
hypercalcemia, infantile, 1:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Hypercalcemia, Infantile, 1

OMIM : 54
Infantile hypercalcemia is characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. An epidemic of idiopathic infantile hypercalcemia occurred in the United Kingdom in the 1950s after the implementation of an increased prophylactic dose of vitamin D supplementation; however, the fact that most infants receiving the prophylaxis remained unaffected suggested that an intrinsic hypersensitivity to vitamin D might be implicated in the pathogenesis (summary by Schlingmann et al., 2011). (143880)

MalaCards based summary : Hypercalcemia, Infantile, 1, also known as idiopathic hypercalcemia of infancy, is related to familial hypocalciuric hypercalcemia and hypocalciuric hypercalcemia, type i, and has symptoms including failure to thrive, nephrolithiasis and nephrocalcinosis. An important gene associated with Hypercalcemia, Infantile, 1 is CYP24A1 (Cytochrome P450 Family 24 Subfamily A Member 1), and among its related pathways/superpathways are Peptide ligand-binding receptors and Presynaptic function of Kainate receptors. The drugs Ergocalciferol and Vitamin D have been mentioned in the context of this disorder. Affiliated tissues include bone and eye, and related phenotypes are growth/size/body region and craniofacial

UniProtKB/Swiss-Prot : 71 Hypercalcemia, infantile, 1: A disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis.

Related Diseases for Hypercalcemia, Infantile, 1

Diseases in the Hypercalcemia, Infantile family:

Hypercalcemia, Infantile, 2 Hypercalcemia, Infantile, 1
Autosomal Recessive Infantile Hypercalcemia

Diseases related to Hypercalcemia, Infantile, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 73)
id Related Disease Score Top Affiliating Genes
1 familial hypocalciuric hypercalcemia 12.3
2 hypocalciuric hypercalcemia, type i 12.3
3 hypocalciuric hypercalcemia, type iii 12.3
4 hypocalciuric hypercalcemia, type ii 12.2
5 hypercalcemia, infantile, 2 12.2
6 hypercalcemia, infantile 11.9
7 cerebrooculofacioskeletal syndrome 4 10.5 CASR PTHLH
8 photoallergic dermatitis 10.4 PTH PTHLH
9 pineal gland cancer 10.4 PTH PTHLH
10 hypodermyasis 10.4 CALCA PTHLH
11 teratocarcinoma 10.4 PTH PTHLH
12 bullous impetigo 10.3 CASR PRKAR1A
13 brain angioma 10.3 PTH PTHLH
14 ophn1 syndrome 10.3 PTH PTHLH
15 hypocalcemia, autosomal dominant 10.3 CASR PRKAR1A
16 hypochondrogenesis 10.3 CALCA PTH
17 kartagener syndrome 10.3 CALCA PTHLH
18 apocrine sweat gland neoplasm 10.3 PTH1R PTHLH
19 mixed cell type adenoma of parathyroid 10.3 CALCA PTH
20 impotence 10.3 PTH PTHLH
21 binocular vision disease 10.3 PTH1R PTHLH
22 hypocalcemia, autosomal dominant 2 10.2 CASR PTH
23 methylmalonic acidemia due to transcobalamin receptor defect 10.2 CASR PTH
24 hypophosphatasia, adult 10.2 CALCA PTH
25 transverse colon cancer 10.2 PTH1R PTHLH
26 pseudohypoparathyroidism, type ib 10.2 PRKAR1A PTH
27 glutaric aciduria iii 10.1 PTH1R PTHLH
28 eiken syndrome 10.1 PTH PTH1R
29 fryns macrocephaly 10.1 PTH1R PTHLH
30 angelman syndrome due to imprinting defect in 15q11-q13 10.1 PTH1R PTHLH
31 multiple endocrine neoplasia iib 10.1 CALCA PTH
32 histiocytoid hemangioma 10.0 CASR VDR
33 anal canal squamous cell carcinoma 10.0 CALCA PTH PTHLH
34 hypercalciuria, absorptive 10.0 CASR VDR
35 xanthomatosis 9.9 CALCA CASR PTH
36 skin fragility-woolly hair-palmoplantar keratoderma syndrome 9.9 PTH1R PTHLH
37 parathyroid carcinoma 9.9 CALCA CASR PTH
38 white sponge nevus of cannon, krt4-related 9.9 PTH VDR
39 xanthinuria, type i 9.9 CASR VDR
40 cri-du-chat syndrome 9.9 PTH1R PTHLH
41 vulvovaginitis 9.9 PTH1R PTHLH
42 immunodeficiency, common variable, 5 9.8 CASR PRKAR1A PTH
43 coffin-lowry syndrome 9.8 PTH VDR
44 obesity, severe bmiq9 9.8 PTH PTH1R PTHLH
45 osteochondrodysplasia 9.8 PTH VDR
46 fibrolamellar carcinoma 9.8 CALCA PTH
47 mutism 9.8 PTH PTH1R PTHLH
48 uv-sensitive syndrome 3 9.8 CASR VDR
49 small cell cancer of the lung, somatic 9.7 PTH PTH1R PTHLH
50 dengue hemorrhagic fever 9.7 CALCA VDR

Graphical network of the top 20 diseases related to Hypercalcemia, Infantile, 1:



Diseases related to Hypercalcemia, Infantile, 1

Symptoms & Phenotypes for Hypercalcemia, Infantile, 1

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Genitourinary- Kidneys:
nephrocalcinosis
polyuria
nephrolithiasis (in some patients)

Neurologic- Central Nervous System:
lethargy

Growth- Weight:
weight loss

Muscle Soft Tissue:
hypotonia

Laboratory- Abnormalities:
hypercalciuria
hypercalcemia
dehydration

Abdomen- Gastroin testinal:
vomiting

Metabolic Features:
suppression of intact parathyroid hormone levels


Clinical features from OMIM:

143880

Human phenotypes related to Hypercalcemia, Infantile, 1:

32 (show all 17)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 nephrolithiasis 32 occasional (7.5%) HP:0000787
3 nephrocalcinosis 32 HP:0000121
4 hypercalciuria 32 HP:0002150
5 lethargy 32 HP:0001254
6 vomiting 32 HP:0002013
7 intellectual disability 32 HP:0001249
8 polyuria 32 HP:0000103
9 pulmonic stenosis 32 HP:0001642
10 muscular hypotonia 32 HP:0001252
11 dehydration 32 HP:0001944
12 weight loss 32 HP:0001824
13 aortic valve stenosis 32 HP:0001650
14 thick lower lip vermilion 32 HP:0000179
15 elfin facies 32 HP:0004428
16 abnormality of the eye 32 HP:0000478
17 infantile hypercalcemia 32 HP:0008250

MGI Mouse Phenotypes related to Hypercalcemia, Infantile, 1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.95 CASR CYP24A1 PRKAR1A PTH PTH1R PTHLH
2 craniofacial MP:0005382 9.88 PRKAR1A PTH PTH1R PTHLH VDR
3 homeostasis/metabolism MP:0005376 9.87 CASR CYP24A1 PRKAR1A PTH PTH1R PTHLH
4 digestive/alimentary MP:0005381 9.85 CASR PRKAR1A PTH1R PTHLH VDR
5 endocrine/exocrine gland MP:0005379 9.83 PRKAR1A PTH PTHLH VDR CASR
6 hematopoietic system MP:0005397 9.77 CASR PRKAR1A PTH PTHLH VDR
7 immune system MP:0005387 9.65 CASR PRKAR1A PTH PTHLH VDR
8 mortality/aging MP:0010768 9.5 VDR CASR CYP24A1 PRKAR1A PTH PTH1R
9 limbs/digits/tail MP:0005371 9.46 VDR PTH PTH1R PTHLH
10 skeleton MP:0005390 9.17 CASR CYP24A1 PRKAR1A PTH PTH1R PTHLH

Drugs & Therapeutics for Hypercalcemia, Infantile, 1

Drugs for Hypercalcemia, Infantile, 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ergocalciferol Approved, Nutraceutical 50-14-6 5280793
2
Vitamin D Approved, Nutraceutical, Vet_approved 1406-16-2
3 Bone Density Conservation Agents
4 Ergocalciferols
5 Micronutrients
6 Trace Elements
7 Vitamins
8 Calciferol Nutraceutical
9 Vitamin D2 Nutraceutical

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria Not yet recruiting NCT03301038 Phase 2 Rifampin
2 Vitamin D Metabolism and the Williams Syndrome Completed NCT00013962 Vitamin D

Search NIH Clinical Center for Hypercalcemia, Infantile, 1

Inferred drug relations via UMLS 69 / NDF-RT 48 :


Cochrane evidence based reviews: hypercalcemia

Genetic Tests for Hypercalcemia, Infantile, 1

Genetic tests related to Hypercalcemia, Infantile, 1:

id Genetic test Affiliating Genes
1 Idiopathic Hypercalcemia of Infancy 29

Anatomical Context for Hypercalcemia, Infantile, 1

MalaCards organs/tissues related to Hypercalcemia, Infantile, 1:

39
Bone, Eye

Publications for Hypercalcemia, Infantile, 1

Variations for Hypercalcemia, Infantile, 1

UniProtKB/Swiss-Prot genetic disease variations for Hypercalcemia, Infantile, 1:

71
id Symbol AA change Variation ID SNP ID
1 CYP24A1 p.Leu409Ser VAR_048466 rs6068812
2 CYP24A1 p.Arg159Gln VAR_066409 rs387907322
3 CYP24A1 p.Glu322Lys VAR_066410 rs387907324
4 CYP24A1 p.Arg396Trp VAR_066411 rs114368325

ClinVar genetic disease variations for Hypercalcemia, Infantile, 1:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 CYP24A1 NM_000782.4(CYP24A1): c.1426_1427delCT (p.Cys477Leufs) deletion Pathogenic rs876657376 GRCh37 Chromosome 20, 52773934: 52773935
2 CYP24A1 NM_000782.4(CYP24A1): c.476G> A (p.Arg159Gln) single nucleotide variant Pathogenic rs387907322 GRCh37 Chromosome 20, 52788183: 52788183
3 CYP24A1 NM_000782.4(CYP24A1): c.428_430delAAG (p.Glu143del) deletion Pathogenic rs777676129 GRCh37 Chromosome 20, 52789467: 52789469
4 CYP24A1 NM_000782.4(CYP24A1): c.451G> T (p.Glu151Ter) single nucleotide variant Pathogenic rs387907323 GRCh37 Chromosome 20, 52788208: 52788208
5 CYP24A1 NM_000782.4(CYP24A1): c.1186C> T (p.Arg396Trp) single nucleotide variant Pathogenic rs114368325 GRCh37 Chromosome 20, 52774675: 52774675
6 CYP24A1 NM_000782.4(CYP24A1): c.1226T> C (p.Leu409Ser) single nucleotide variant Pathogenic rs6068812 GRCh37 Chromosome 20, 52774635: 52774635
7 CYP24A1 NM_000782.4(CYP24A1): c.964G> A (p.Glu322Lys) single nucleotide variant Pathogenic rs387907324 GRCh37 Chromosome 20, 52779282: 52779282
8 CYP24A1 NM_000782.4(CYP24A1): c.1039C> T (p.Gln347Ter) single nucleotide variant Likely pathogenic rs777947329 GRCh38 Chromosome 20, 54159075: 54159075

Expression for Hypercalcemia, Infantile, 1

Search GEO for disease gene expression data for Hypercalcemia, Infantile, 1.

Pathways for Hypercalcemia, Infantile, 1

Pathways related to Hypercalcemia, Infantile, 1 according to GeneCards Suite gene sharing:

(show all 11)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.16 CALCA CASR PTH PTH1R PTHLH
2
Show member pathways
12.02 CALCA PTH PTH1R PTHLH
3 11.72 CALCA PTH PTH1R PTHLH
4 11.68 CASR PRKAR1A VDR
5 11.36 PTH PTH1R PTHLH
6 11.15 PTH1R VDR
7 11.01 CALCA CYP24A1 PTH PTH1R VDR
8 11 CYP24A1 VDR
9 10.61 PRKAR1A PTH PTH1R PTHLH VDR
10 10.58 PTH PTH1R
11 10.33 CYP24A1 PTH VDR

GO Terms for Hypercalcemia, Infantile, 1

Biological processes related to Hypercalcemia, Infantile, 1 according to GeneCards Suite gene sharing:

(show all 16)
id Name GO ID Score Top Affiliating Genes
1 cell-cell signaling GO:0007267 9.72 CALCA PTH PTHLH
2 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007200 9.56 CASR PTH1R
3 vasodilation GO:0042311 9.54 CALCA CASR
4 bone resorption GO:0045453 9.52 PTH PTH1R
5 response to vitamin D GO:0033280 9.51 CYP24A1 PTH
6 negative regulation of chondrocyte differentiation GO:0032331 9.49 PTH PTHLH
7 osteoblast development GO:0002076 9.48 PTH1R PTHLH
8 positive regulation of ossification GO:0045778 9.46 CALCA PTH
9 skeletal system development GO:0001501 9.46 PTH PTH1R PTHLH VDR
10 positive regulation of inositol phosphate biosynthetic process GO:0060732 9.43 PTH PTH1R
11 positive regulation of cAMP biosynthetic process GO:0030819 9.43 CALCA PTH PTHLH
12 response to fibroblast growth factor GO:0071774 9.4 CASR PTH
13 cAMP metabolic process GO:0046058 9.37 PTH PTHLH
14 vitamin D receptor signaling pathway GO:0070561 9.32 CYP24A1 VDR
15 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007189 9.26 CALCA PTH PTH1R PTHLH
16 cellular calcium ion homeostasis GO:0006874 9.02 CALCA CASR PTH PTH1R VDR

Molecular functions related to Hypercalcemia, Infantile, 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 peptide hormone receptor binding GO:0051428 8.96 PTH PTHLH
2 hormone activity GO:0005179 8.8 CALCA PTH PTHLH

Sources for Hypercalcemia, Infantile, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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