MCID: VTM008
MIFTS: 38

Vitamin D-Dependent Rickets, Type I

Categories: Genetic diseases

Aliases & Classifications for Vitamin D-Dependent Rickets, Type I

MalaCards integrated aliases for Vitamin D-Dependent Rickets, Type I:

Name: Vitamin D-Dependent Rickets, Type I 54 13
Pseudovitamin D Deficiency Rickets 24 71
25-Hydroxycholecalciferol-1-Hydroxylase Deficiency 71
1-Alpha 25-Hydroxyvitamin D3 Deficiency Selective 71
Pseudovitamin D-Deficiency Rickets Type Ia 71
Vitamin D-Dependent Rickets, Type 1 69
Vitamin D-Dependent Rickets Type I 24
1 Alpha Hydroxylase Deficiency 24
1-Alpha-Hydroxylase Deficiency 71
Rickets Vitamin D-Dependent 1a 71
Vitamin D Dependency Type 1 71
Pddr Ia 71
Pddr1a 71
Vddr1a 71
Pddr 71
Vdd1 71

Characteristics:

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
clinical onset within first 2 years of life
can be treated with physiologic levels of 1,25-dihydroxyvitamin d3 or 1-alpha-hydroxyvitamin d3
increased frequency among french-canadians from the charlevoix-saguenay-lac saint jean area of quebec (carrier rate 1 in 26)


HPO:

32
vitamin d-dependent rickets, type i:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Vitamin D-Dependent Rickets, Type I

OMIM : 54
Vitamin D3 (cholecalciferol), synthesized in the epidermis in response to UV radiation, and dietary vitamin D2 (ergocalciferol, synthesized in plants) are devoid of any biologic activity. Vitamin D hormonal activity is due primarily to the hydroxylated metabolite of vitamin D3, 1-alpha,25-dihydroxyvitamin D3 (calcitriol), the actions of which are mediated by the vitamin D receptor (VDR; 601769) (Koren, 2006; Liberman and Marx, 2001). In the liver, vitamin D 25-hydroxylase (CYP2R1; 608713) catalyzes the initial hydroxylation of vitamin D at carbon 25; in the kidney, 1-alpha-hydroxylase (CYP27B1; 609506) catalyzes the hydroxylation and metabolic activation of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3. The active metabolite 1,25(OH)2D3 binds and activates the nuclear vitamin D receptor, with subsequent regulation of physiologic events such as calcium homeostasis and cellular differentiation and proliferation (Takeyama et al., 1997). Disorders of vitamin D metabolism or action lead to defective bone mineralization and clinical features including intestinal malabsorption of calcium, hypocalcemia, secondary hyperparathyroidism, increased renal clearance of phosphorus, and hypophosphatemia. The combination of hypocalcemia and hypophosphatemia causes impaired mineralization of bone that results in rickets and osteomalacia (Liberman and Marx, 2001). (264700)

MalaCards based summary : Vitamin D-Dependent Rickets, Type I, also known as pseudovitamin d deficiency rickets, is related to hypocalcemic vitamin d-dependent rickets and rickets, vitamin d-resistant, type iia, and has symptoms including failure to thrive, irritability and femoral bowing. An important gene associated with Vitamin D-Dependent Rickets, Type I is CYP27B1 (Cytochrome P450 Family 27 Subfamily B Member 1), and among its related pathways/superpathways are Cytochrome P450 - arranged by substrate type and Vitamin D Metabolism. Affiliated tissues include bone, liver and kidney, and related phenotype is cardiovascular system.

UniProtKB/Swiss-Prot : 71 Rickets vitamin D-dependent 1A: A disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets.

Related Diseases for Vitamin D-Dependent Rickets, Type I

Diseases in the Vitamin D-Dependent Rickets, Type I family:

Vitamin D-Dependent Rickets Type Ii

Diseases related to Vitamin D-Dependent Rickets, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 hypocalcemic vitamin d-dependent rickets 11.4
2 rickets, vitamin d-resistant, type iia 10.8
3 rickets 10.5
4 cerebrotendinous xanthomatosis 10.0
5 xanthomatosis 10.0
6 bone deterioration disease 9.4 CYP27A1 CYP27B1
7 keratosis pilaris atrophicans 8.8 CYP27A1 CYP27B1 FDX1
8 aneurysm, intracranial berry, 9 8.6 CYP27A1 CYP27B1 FDX1

Graphical network of the top 20 diseases related to Vitamin D-Dependent Rickets, Type I:



Diseases related to Vitamin D-Dependent Rickets, Type I

Symptoms & Phenotypes for Vitamin D-Dependent Rickets, Type I

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive
growth retardation
poor growth

Neurologic- Central Nervous System:
delayed motor development
seizures due to hypocalcemia

Head And Neck- Head:
frontal bossing

Head And Neck- Teeth:
enamel hypoplasia
delayed tooth eruption

Chest- Ribs Sternum Clavicles And Scapulae:
enlargement of the costochondral junction
'bulging' of the costochondral junction
deformed rib cage

Skeletal- Limbs:
delayed opacification of the epiphyses
widened, distorted epiphyses
'bulging' epiphyses
frayed, irregular metaphyses
lower limb deformities
more
Endocrine Features:
secondary hyperparathyroidism

Muscle Soft Tissue:
hypotonia
muscle weakness
difficulty walking
difficulty standing

Neurologic- Behavioral Psychiatric Manifestations:
irritability

Skeletal:
bone pain
rickets
increased fractures
sparse bone trabeculae
thin bony cortex

Laboratory- Abnormalities:
hypocalcemia
increased serum alkaline phosphatase
generalized aminoaciduria
hypophosphatemia
increased serum parathyroid hormone (pth)
more
Skeletal- Skull:
widened cranial sutures
posterior flattening of the skull

Abdomen- External Features:
protuberant abdomen due to muscle weakness


Clinical features from OMIM:

264700

Human phenotypes related to Vitamin D-Dependent Rickets, Type I:

32 (show all 38)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 irritability 32 HP:0000737
3 femoral bowing 32 HP:0002980
4 tibial bowing 32 HP:0002982
5 frontal bossing 32 HP:0002007
6 protuberant abdomen 32 HP:0001538
7 motor delay 32 HP:0001270
8 recurrent fractures 32 HP:0002757
9 bone pain 32 HP:0002653
10 hypocalcemic seizures 32 HP:0002199
11 muscular hypotonia 32 HP:0001252
12 generalized aminoaciduria 32 HP:0002909
13 difficulty walking 32 HP:0002355
14 hypophosphatemia 32 HP:0002148
15 rickets 32 HP:0002748
16 flat occiput 32 HP:0005469
17 elevated alkaline phosphatase 32 HP:0003155
18 enlargement of the costochondral junction 32 HP:0000920
19 deformed rib cage 32 HP:0000886
20 sparse bone trabeculae 32 HP:0002752
21 thin bony cortex 32 HP:0002753
22 bowing of the legs 32 HP:0002979
23 enlargement of the wrists 32 HP:0003020
24 enlargement of the ankles 32 HP:0003029
25 difficulty standing 32 HP:0003698
26 growth delay 32 HP:0001510
27 delayed eruption of teeth 32 HP:0000684
28 secondary hyperparathyroidism 32 HP:0000867
29 metaphyseal irregularity 32 HP:0003025
30 delayed epiphyseal ossification 32 HP:0002663
31 abdominal wall muscle weakness 32 HP:0009023
32 elevated circulating parathyroid hormone level 32 HP:0003165
33 hypoplasia of dental enamel 32 HP:0006297
34 widely patent fontanelles and sutures 32 HP:0004492
35 fibular bowing 32 HP:0010502
36 bulging epiphyses 32 HP:0003013
37 bulging of the costochondral junction 32 HP:0000893
38 subperiosteal bone resorption 32 HP:0003106

UMLS symptoms related to Vitamin D-Dependent Rickets, Type I:


muscle weakness, bone pain, difficulty standing

MGI Mouse Phenotypes related to Vitamin D-Dependent Rickets, Type I:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 8.8 CYP27A1 CYP27B1 FDX1

Drugs & Therapeutics for Vitamin D-Dependent Rickets, Type I

Search Clinical Trials , NIH Clinical Center for Vitamin D-Dependent Rickets, Type I

Genetic Tests for Vitamin D-Dependent Rickets, Type I

Genetic tests related to Vitamin D-Dependent Rickets, Type I:

id Genetic test Affiliating Genes
1 Vitamin D-Dependent Rickets Type I 24 CYP27B1

Anatomical Context for Vitamin D-Dependent Rickets, Type I

MalaCards organs/tissues related to Vitamin D-Dependent Rickets, Type I:

39
Bone, Liver, Kidney, Cortex

Publications for Vitamin D-Dependent Rickets, Type I

Articles related to Vitamin D-Dependent Rickets, Type I:

(show all 12)
id Title Authors Year
1
Fibroblast growth factor-23 and renin-angiotensin system levels in vitamin-D-dependent rickets type I. ( 26939683 )
2016
2
Genotype and Phenotype Characteristics in 22 Patients with Vitamin D-Dependent Rickets Type I. ( 26982175 )
2016
3
First Australian report of vitamin D-dependent rickets type I. ( 25296067 )
2014
4
Novel vitamin D 1I+-hydroxylase gene mutations in a Chinese vitamin-D-dependent rickets type I patient. ( 21869486 )
2011
5
Vitamin D dependent rickets type I. ( 21503197 )
2011
6
Oral and dental manifestations of vitamin D-dependent rickets type I: report of a pediatric case. ( 12789152 )
2003
7
Structure-function analysis of CYP27B1 and CYP27A1. Studies on mutants from patients with vitamin D-dependent rickets type I (VDDR-I) and cerebrotendinous xanthomatosis (CTX). ( 11737215 )
2001
8
The molecular basis of vitamin D-dependent rickets type I. ( 11603564 )
2001
9
Genetic mutation in the human 25-hydroxyvitamin D3 1alpha-hydroxylase gene causes vitamin D-dependent rickets type I. ( 10612418 )
1999
10
Vitamin D-dependent rickets type I and type II. ( 9316302 )
1997
11
Effect of 1,25-dihydroxyvitamin D3 on plasma concentrations of calcium-binding protein in normal and rachitic (vitamin D-dependent rickets type I) pigs. ( 3668440 )
1987
12
Vitamin D-dependent rickets type I in pigs. ( 2996825 )
1985

Variations for Vitamin D-Dependent Rickets, Type I

UniProtKB/Swiss-Prot genetic disease variations for Vitamin D-Dependent Rickets, Type I:

71 (show all 18)
id Symbol AA change Variation ID SNP ID
1 CYP27B1 p.Arg107His VAR_016952 rs28934604
2 CYP27B1 p.Gly125Glu VAR_016953 rs28934605
3 CYP27B1 p.Glu189Gly VAR_016954 rs118204012
4 CYP27B1 p.Thr321Arg VAR_016955 rs118204007
5 CYP27B1 p.Arg335Pro VAR_016956 rs28934606
6 CYP27B1 p.Leu343Phe VAR_016957 rs118204011
7 CYP27B1 p.Pro382Ser VAR_016958 rs28934607
8 CYP27B1 p.Arg389His VAR_016959 rs118204009
9 CYP27B1 p.Arg389Gly VAR_016960 rs118204010
10 CYP27B1 p.Thr409Ile VAR_016961 rs118204008
11 CYP27B1 p.Glu189Lys VAR_016967
12 CYP27B1 p.Arg389Cys VAR_016968 rs118204010
13 CYP27B1 p.Gln65His VAR_016969 rs868704228
14 CYP27B1 p.Ser323Tyr VAR_016970
15 CYP27B1 p.Arg429Pro VAR_016971
16 CYP27B1 p.Arg453Cys VAR_016972 rs767480544
17 CYP27B1 p.Val478Gly VAR_016973
18 CYP27B1 p.Pro497Arg VAR_016974

ClinVar genetic disease variations for Vitamin D-Dependent Rickets, Type I:

6 (show all 18)
id Gene Variation Type Significance SNP ID Assembly Location
1 CYP27B1 NM_000785.3(CYP27B1): c.320G> A (p.Arg107His) single nucleotide variant Pathogenic/Likely pathogenic rs28934604 GRCh37 Chromosome 12, 58159856: 58159856
2 CYP27B1 NM_000785.3(CYP27B1): c.374G> A (p.Gly125Glu) single nucleotide variant Pathogenic rs28934605 GRCh37 Chromosome 12, 58159802: 58159802
3 CYP27B1 NM_000785.3(CYP27B1): c.1004G> C (p.Arg335Pro) single nucleotide variant Pathogenic rs28934606 GRCh37 Chromosome 12, 58158293: 58158293
4 CYP27B1 NM_000785.3(CYP27B1): c.1144C> T (p.Pro382Ser) single nucleotide variant Pathogenic rs28934607 GRCh37 Chromosome 12, 58157952: 58157952
5 CYP27B1 NM_000785.3(CYP27B1): c.630delG (p.Glu211Argfs) deletion Pathogenic rs387906258 GRCh37 Chromosome 12, 58158954: 58158954
6 CYP27B1 NM_000785.3(CYP27B1): c.692delC (p.Thr232Argfs) deletion Pathogenic rs387906259 GRCh37 Chromosome 12, 58158892: 58158892
7 CYP27B1 NM_000785.3(CYP27B1): c.262delG (p.Val88Trpfs) deletion Pathogenic rs387906260 GRCh37 Chromosome 12, 58159914: 58159914
8 CYP27B1 CYP27B1, 7-BP DUP duplication Pathogenic
9 CYP27B1 NM_000785.3(CYP27B1): c.962C> G (p.Thr321Arg) single nucleotide variant Pathogenic rs118204007 GRCh37 Chromosome 12, 58158538: 58158538
10 CYP27B1 NM_000785.3(CYP27B1): c.589+1G> A single nucleotide variant Pathogenic rs761780097 GRCh37 Chromosome 12, 58159079: 58159079
11 CYP27B1 NM_000785.3(CYP27B1): c.1226C> T (p.Thr409Ile) single nucleotide variant Pathogenic rs118204008 GRCh37 Chromosome 12, 58157581: 58157581
12 CYP27B1 NM_000785.3(CYP27B1): c.1166G> A (p.Arg389His) single nucleotide variant Pathogenic/Likely pathogenic rs118204009 GRCh37 Chromosome 12, 58157930: 58157930
13 CYP27B1 CYP27B1, 5-BP DEL/6-BP INS indel Pathogenic
14 CYP27B1 CYP27B1, IVS2, G-A, +1 single nucleotide variant Pathogenic
15 CYP27B1 NM_000785.3(CYP27B1): c.1165C> G (p.Arg389Gly) single nucleotide variant Pathogenic rs118204010 GRCh37 Chromosome 12, 58157931: 58157931
16 CYP27B1 NM_000785.3(CYP27B1): c.1027C> T (p.Leu343Phe) single nucleotide variant Pathogenic rs118204011 GRCh37 Chromosome 12, 58158270: 58158270
17 CYP27B1 NM_000785.3(CYP27B1): c.566A> G (p.Glu189Gly) single nucleotide variant Pathogenic rs118204012 GRCh37 Chromosome 12, 58159103: 58159103
18 CYP27B1 NM_000785.3(CYP27B1): c.1319_1325dupCCCACCC (p.Phe443Profs) duplication Pathogenic rs780950819 GRCh37 Chromosome 12, 58157482: 58157482

Expression for Vitamin D-Dependent Rickets, Type I

Search GEO for disease gene expression data for Vitamin D-Dependent Rickets, Type I.

Pathways for Vitamin D-Dependent Rickets, Type I

GO Terms for Vitamin D-Dependent Rickets, Type I

Cellular components related to Vitamin D-Dependent Rickets, Type I according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 9.16 CYP27A1 FDX1
2 mitochondrion GO:0005739 9.13 CYP27A1 CYP27B1 FDX1
3 mitochondrial membrane GO:0031966 8.62 CYP27A1 CYP27B1

Biological processes related to Vitamin D-Dependent Rickets, Type I according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 oxidation-reduction process GO:0055114 9.13 CYP27A1 CYP27B1 FDX1
2 sterol metabolic process GO:0016125 8.62 CYP27A1 FDX1

Molecular functions related to Vitamin D-Dependent Rickets, Type I according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 heme binding GO:0020037 9.16 CYP27A1 CYP27B1
2 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen GO:0016705 8.96 CYP27A1 CYP27B1
3 iron ion binding GO:0005506 8.8 CYP27A1 CYP27B1 FDX1

Sources for Vitamin D-Dependent Rickets, Type I

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
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43 MESH via Orphanet
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48 NDF-RT
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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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