HCINF1
MCID: HYP726
MIFTS: 55

Hypercalcemia, Infantile, 1 (HCINF1)

Categories: Genetic diseases, Nephrological diseases

Aliases & Classifications for Hypercalcemia, Infantile, 1

MalaCards integrated aliases for Hypercalcemia, Infantile, 1:

Name: Hypercalcemia, Infantile, 1 57 75
Idiopathic Hypercalcemia of Infancy 75 29 6
Hypercalcemia Infantile 75 37
Hypercalcemia 44 73
Hcinf1 57 75
Hypercalcemia, Idiopathic, of Infancy 57
Hypercalcemia, Infantile, Type 1 40
Hypercalcemia, Infantile 13

Characteristics:

OMIM:

57
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 : 57 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 hypocalciuric hypercalcemia, familial, type i and hypocalciuric hypercalcemia, familial, type ii. 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 Steroid biosynthesis and Peptide ligand-binding receptors. Affiliated tissues include lung, kidney and bone, and related phenotypes are intellectual disability and failure to thrive

UniProtKB/Swiss-Prot : 75 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, 1 family:

Hypercalcemia, Infantile, 2

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

(show top 50) (show all 485)
# Related Disease Score Top Affiliating Genes
1 hypocalciuric hypercalcemia, familial, type i 34.2 PTH CASR
2 hypocalciuric hypercalcemia, familial, type ii 34.1 PTH CASR
3 familial hypocalciuric hypercalcemia 34.1 PTH CASR
4 hypocalciuric hypercalcemia, familial, type iii 34.0 PTHLH PTH CASR
5 hyperparathyroidism, neonatal severe 32.7 PRKAR1A CASR
6 parathyroid carcinoma 31.9 PTH CASR CALCA
7 familial isolated hyperparathyroidism 31.7 PTH CASR
8 metaphyseal chondrodysplasia, jansen type 31.4 PTHLH PTH1R PTH CALCA
9 primary hyperparathyroidism 31.1 CALCA CASR PRKAR1A PTH PTH1R PTHLH
10 hypocalcemia, autosomal dominant 1 31.1 VDR PTH PRKAR1A CASR CALCA
11 nephrocalcinosis 30.3 PTH CYP24A1 CASR
12 bone resorption disease 30.0 VDR PTH CALCA
13 multiple endocrine neoplasia 30.0 PRKAR1A CALCA
14 hyperparathyroidism 29.8 VDR PTHLH PTH PRKAR1A CASR CALCA
15 islet cell tumor 29.8 PTHLH CALCA
16 hypoparathyroidism 29.8 PTHLH PTH1R PTH CASR
17 hypervitaminosis d 29.8 VDR PTH
18 sclerosing hepatic carcinoma 29.7 PTHLH PTH
19 hyperphosphatemia 29.7 VDR PTH CASR
20 parathyroid adenoma 29.6 VDR PTHLH PTH CASR CALCA
21 nephrolithiasis 29.5 VDR PTH CYP24A1 CASR
22 hypoadrenalism 29.5 PTHLH CALCA
23 multiple endocrine neoplasia, type i 29.4 PTH PRKAR1A CASR
24 nephrolithiasis, calcium oxalate 29.4 VDR CASR
25 secondary hyperparathyroidism of renal origin 29.3 VDR PTH CASR CALCA
26 paget's disease of bone 29.2 PTH CALCA
27 osteitis fibrosa 29.2 PTH CASR CALCA
28 renal osteodystrophy 29.2 VDR PTH CASR CALCA
29 hypophosphatemic rickets, x-linked recessive 29.2 VDR CYP24A1
30 kidney disease 29.1 VDR PTH CASR
31 pseudohypoparathyroidism 29.1 PTHLH PTH1R PTH
32 calciphylaxis 29.0 VDR PTH CASR
33 bone disease 28.8 VDR PTHLH PTH1R PTH CASR CALCA
34 osteomalacia 28.8 VDR PTH CYP24A1 CASR CALCA
35 chronic kidney failure 28.8 VDR PTH1R PTH CASR CALCA
36 parathyroid gland disease 28.6 VDR PTHLH PTH CASR CALCA
37 osteoporosis 28.2 VDR PTHLH PTH1R PTH PRKAR1A CYP24A1
38 idiopathic infantile hypercalcemia 12.6
39 blue diaper syndrome 12.0
40 hyperparathyroidism 2 with jaw tumors 11.4
41 myeloma, multiple 11.3
42 hypophosphatasia 11.3
43 rickets 11.3
44 hypophosphatasia, infantile 11.2
45 vipoma 11.2
46 williams-beuren syndrome 11.2
47 hypercalcemia, infantile, 2 11.1
48 hyperparathyroidism 1 10.9
49 intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, and genital anomalies 10.9
50 hyperparathyroidism 4 10.9

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:

57
Growth Other:
failure to thrive

Abdomen Gastrointestinal:
vomiting

Genitourinary Kidneys:
nephrocalcinosis
polyuria
nephrolithiasis (in some patients)

Muscle Soft Tissue:
hypotonia

Laboratory Abnormalities:
dehydration
hypercalciuria
hypercalcemia

Growth Weight:
weight loss

Neurologic Central Nervous System:
lethargy

Metabolic Features:
suppression of intact parathyroid hormone levels


Clinical features from OMIM:

143880

Human phenotypes related to Hypercalcemia, Infantile, 1:

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 failure to thrive 32 HP:0001508
3 dehydration 32 HP:0001944
4 vomiting 32 HP:0002013
5 abnormality of the eye 32 HP:0000478
6 weight loss 32 HP:0001824
7 thick lower lip vermilion 32 HP:0000179
8 hypercalciuria 32 HP:0002150
9 nephrocalcinosis 32 HP:0000121
10 nephrolithiasis 32 occasional (7.5%) HP:0000787
11 pulmonic stenosis 32 HP:0001642
12 elfin facies 32 HP:0004428
13 lethargy 32 HP:0001254
14 generalized hypotonia 32 HP:0001290
15 aortic valve stenosis 32 HP:0001650
16 infantile hypercalcemia 32 HP:0008250
17 polyuria 32 HP:0000103

MGI Mouse Phenotypes related to Hypercalcemia, Infantile, 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.95 CASR CYP24A1 PRKAR1A PTH PTH1R PTHLH
2 endocrine/exocrine gland MP:0005379 9.91 CASR PRKAR1A PTH PTH1R PTHLH VDR
3 craniofacial MP:0005382 9.88 PRKAR1A PTH PTH1R PTHLH VDR
4 homeostasis/metabolism MP:0005376 9.87 CASR CYP24A1 PRKAR1A PTH PTH1R PTHLH
5 digestive/alimentary MP:0005381 9.85 CASR PRKAR1A PTH1R PTHLH VDR
6 hematopoietic system MP:0005397 9.85 CASR PRKAR1A PTH PTH1R PTHLH VDR
7 immune system MP:0005387 9.73 CASR PRKAR1A PTH PTH1R PTHLH VDR
8 mortality/aging MP:0010768 9.5 CASR CYP24A1 PRKAR1A PTH PTH1R PTHLH
9 limbs/digits/tail MP:0005371 9.46 PTH PTH1R PTHLH VDR
10 skeleton MP:0005390 9.17 CASR CYP24A1 PRKAR1A PTH PTH1R PTHLH

Drugs & Therapeutics for Hypercalcemia, Infantile, 1

Genetic Tests for Hypercalcemia, Infantile, 1

Genetic tests related to Hypercalcemia, Infantile, 1:

# Genetic test Affiliating Genes
1 Idiopathic Hypercalcemia of Infancy 29 CYP24A1

Anatomical Context for Hypercalcemia, Infantile, 1

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

41
Lung, Kidney, Bone, Eye, Thyroid, T Cells, Myeloid

Publications for Hypercalcemia, Infantile, 1

Articles related to Hypercalcemia, Infantile, 1:

(show all 20)
# Title Authors Year
1
50 years ago in the Journal of Pediatrics: metabolic studies in a patient with idiopathic hypercalcemia of infancy. ( 23527844 )
2013
2
Coarctation of the aorta with multiple artery anomalies in idiopathic hypercalcemia of infancy. ( 5378351 )
1969
3
Idiopathic hypercalcemia of infancy with interruption of the aortic arch. ( 5661210 )
1968
4
A study of vitamin D metabolism in idiopathic hypercalcemia of infancy. ( 5972562 )
1966
5
Idiopathic hypercalcemia of infancy: optic atrophy and other ocular changes. ( 5883818 )
1965
6
IDIOPATHIC HYPERCALCEMIA OF INFANCY. ( 14284063 )
1965
7
IDIOPATHIC HYPERCALCEMIA OF INFANCY SIMULATING CONGENITAL HEART DISEASE. ( 14338463 )
1965
8
Metabolic studies in a patient with idiopathic hypercalcemia of infancy. ( 14031980 )
1963
9
Cardiac findings in idiopathic hypercalcemia of infancy. ( 13739645 )
1961
10
Idiopathic hypercalcemia of infancy. ( 14425916 )
1960
11
Idiopathic hypercalcemia of infancy. ( 14428009 )
1960
12
Idiopathic hypercalcemia of infancy. ( 13645098 )
1959
13
Idiopathic hypercalcemia of infancy and vitamin D metabolism. ( 13822111 )
1959
14
Idiopathic hypercalcemia of infancy: report of a case and a review of the literature. ( 13845201 )
1959
15
Idiopathic hypercalcemia of infancy. ( 13570850 )
1958
16
Severe idiopathic hypercalcemia of infancy. ( 13571500 )
1958
17
Etiology of the severe form of idiopathic hypercalcemia of infancy; a defect in vitamin D metabolism. ( 13600622 )
1958
18
Severe idiopathic hypercalcemia of infancy. ( 13408014 )
1957
19
The radiographic features of severe idiopathic hypercalcemia of infancy. ( 13441901 )
1957
20
Idiopathic hypercalcemia of infancy, with failure to thrive; report of three cases, with a consideration of the possible etiology. ( 13483867 )
1957

Variations for Hypercalcemia, Infantile, 1

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

75
# 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 (show all 20)
# 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.1426_1427delCT (p.Cys477Leufs) deletion Pathogenic rs876657376 GRCh38 Chromosome 20, 54157395: 54157396
3 CYP24A1 NM_000782.4(CYP24A1): c.476G> A (p.Arg159Gln) single nucleotide variant Pathogenic rs387907322 GRCh37 Chromosome 20, 52788183: 52788183
4 CYP24A1 NM_000782.4(CYP24A1): c.476G> A (p.Arg159Gln) single nucleotide variant Pathogenic rs387907322 GRCh38 Chromosome 20, 54171644: 54171644
5 CYP24A1 NM_000782.4(CYP24A1): c.428_430delAAG (p.Glu143del) deletion Pathogenic rs777676129 GRCh37 Chromosome 20, 52789467: 52789469
6 CYP24A1 NM_000782.4(CYP24A1): c.428_430delAAG (p.Glu143del) deletion Pathogenic rs777676129 GRCh38 Chromosome 20, 54172928: 54172930
7 CYP24A1 NM_000782.4(CYP24A1): c.451G> T (p.Glu151Ter) single nucleotide variant Pathogenic rs387907323 GRCh37 Chromosome 20, 52788208: 52788208
8 CYP24A1 NM_000782.4(CYP24A1): c.451G> T (p.Glu151Ter) single nucleotide variant Pathogenic rs387907323 GRCh38 Chromosome 20, 54171669: 54171669
9 CYP24A1 NM_000782.4(CYP24A1): c.1186C> T (p.Arg396Trp) single nucleotide variant Pathogenic rs114368325 GRCh37 Chromosome 20, 52774675: 52774675
10 CYP24A1 NM_000782.4(CYP24A1): c.1186C> T (p.Arg396Trp) single nucleotide variant Pathogenic rs114368325 GRCh38 Chromosome 20, 54158136: 54158136
11 CYP24A1 NM_000782.4(CYP24A1): c.1226T> C (p.Leu409Ser) single nucleotide variant Pathogenic rs6068812 GRCh37 Chromosome 20, 52774635: 52774635
12 CYP24A1 NM_000782.4(CYP24A1): c.1226T> C (p.Leu409Ser) single nucleotide variant Pathogenic rs6068812 GRCh38 Chromosome 20, 54158096: 54158096
13 CYP24A1 NM_000782.4(CYP24A1): c.964G> A (p.Glu322Lys) single nucleotide variant Pathogenic rs387907324 GRCh37 Chromosome 20, 52779282: 52779282
14 CYP24A1 NM_000782.4(CYP24A1): c.964G> A (p.Glu322Lys) single nucleotide variant Pathogenic rs387907324 GRCh38 Chromosome 20, 54162743: 54162743
15 CYP24A1 NM_000782.4(CYP24A1): c.1039C> T (p.Gln347Ter) single nucleotide variant Likely pathogenic rs777947329 GRCh38 Chromosome 20, 54159075: 54159075
16 CYP24A1 NM_000782.4(CYP24A1): c.1039C> T (p.Gln347Ter) single nucleotide variant Likely pathogenic rs777947329 GRCh37 Chromosome 20, 52775614: 52775614
17 CYP24A1 NM_000782.4(CYP24A1): c.552C> T (p.Ala184=) single nucleotide variant Benign rs2296241 GRCh37 Chromosome 20, 52786219: 52786219
18 CYP24A1 NM_000782.4(CYP24A1): c.552C> T (p.Ala184=) single nucleotide variant Benign rs2296241 GRCh38 Chromosome 20, 54169680: 54169680
19 CASR NM_000388.3(CASR): c.2449G> A (p.Val817Ile) single nucleotide variant Likely pathogenic rs1057518933 GRCh37 Chromosome 3, 122003250: 122003250
20 CASR NM_000388.3(CASR): c.2449G> A (p.Val817Ile) single nucleotide variant Likely pathogenic rs1057518933 GRCh38 Chromosome 3, 122284403: 122284403

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 KEGG:

37
# Name Kegg Source Accession
1 Steroid biosynthesis hsa00100

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

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.16 CALCA CASR PTH PTH1R PTHLH
2
Show member pathways
12.07 CALCA PTH PTH1R PTHLH
3 11.79 CALCA PTH PTH1R PTHLH
4 11.71 CASR PRKAR1A VDR
5 11.39 PTH PTH1R PTHLH
6 11.21 CALCA CYP24A1 PTH PTH1R VDR
7 11.18 PTH1R VDR
8 11.13 CASR CYP24A1 PTH PTH1R PTHLH VDR
9 11.02 CYP24A1 VDR
10 10.94 PRKAR1A PTH PTH1R PTHLH VDR
11 10.6 PTH PTH1R
12 10.43 CYP24A1 PTH VDR

GO Terms for Hypercalcemia, Infantile, 1

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor signaling pathway GO:0007186 9.88 CALCA CASR PTH PTH1R PTHLH
2 negative regulation of cell proliferation GO:0008285 9.75 PTH1R PTHLH VDR
3 cell-cell signaling GO:0007267 9.73 CALCA PTH PTHLH
4 phospholipase C-activating G protein-coupled receptor signaling pathway GO:0007200 9.57 CASR PTH1R
5 bone resorption GO:0045453 9.55 PTH PTH1R
6 response to vitamin D GO:0033280 9.54 CYP24A1 PTH
7 vasodilation GO:0042311 9.52 CALCA CASR
8 osteoblast development GO:0002076 9.51 PTH1R PTHLH
9 negative regulation of chondrocyte differentiation GO:0032331 9.49 PTH PTHLH
10 vitamin D metabolic process GO:0042359 9.46 CYP24A1 VDR
11 skeletal system development GO:0001501 9.46 PTH PTH1R PTHLH VDR
12 positive regulation of inositol phosphate biosynthetic process GO:0060732 9.43 PTH PTH1R
13 bone mineralization GO:0030282 9.43 PTH PTH1R PTHLH
14 response to fibroblast growth factor GO:0071774 9.4 CASR PTH
15 cAMP metabolic process GO:0046058 9.37 PTH PTHLH
16 vitamin D receptor signaling pathway GO:0070561 9.32 CYP24A1 VDR
17 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.26 CALCA PTH PTH1R PTHLH
18 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:

# 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
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
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