VDDR1A
MCID: VTM026
MIFTS: 37

Vitamin D Hydroxylation-Deficient Rickets, Type 1a (VDDR1A)

Categories: Bone diseases, Genetic diseases

Aliases & Classifications for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

MalaCards integrated aliases for Vitamin D Hydroxylation-Deficient Rickets, Type 1a:

Name: Vitamin D Hydroxylation-Deficient Rickets, Type 1a 58
25-Hydroxycholecalciferol-1-Hydroxylase Deficiency 58 76
Vitamin D-Dependent Rickets, Type 1a 58 41
Vitamin D-Dependent Rickets, Type I 58 13
1-Alpha-Hydroxylase Deficiency 58 76
Pddr Ia 58 76
Vddr1a 58 76
Pddr1a 58 76
Vdd1 58 76
1-Alpha, 25-Hydroxyvitamin D3 Deficiency, Selective 58
Pseudovitamin D-Deficiency Rickets, Type Ia; Pddr1a 58
1-Alpha 25-Hydroxyvitamin D3 Deficiency Selective 76
Pseudovitamin D-Deficiency Rickets, Type Ia 58
Pseudovitamin D-Deficiency Rickets Type Ia 76
Vitamin D-Dependent Rickets, Type 1 74
Vitamin D Dependency, Type 1; Vdd1 58
Pseudovitamin D Deficiency Rickets 76
Rickets Vitamin D-Dependent 1a 76
Vitamin D Dependency, Type 1 58
Vitamin D Dependency Type 1 76
Pddr 76

Characteristics:

OMIM:

58
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:

33
vitamin d hydroxylation-deficient rickets, type 1a:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

OMIM : 58 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 Hydroxylation-Deficient Rickets, Type 1a, also known as 25-hydroxycholecalciferol-1-hydroxylase deficiency, is related to hypocalcemic vitamin d-dependent rickets and vitamin d-dependent rickets, type 2a, and has symptoms including muscle weakness, bone pain and difficulty standing. An important gene associated with Vitamin D Hydroxylation-Deficient Rickets, Type 1a is CYP27B1 (Cytochrome P450 Family 27 Subfamily B Member 1). The drugs Parathyroid hormone and Teriparatide have been mentioned in the context of this disorder. Affiliated tissues include kidney, bone and cortex, and related phenotypes are frontal bossing and muscular hypotonia

UniProtKB/Swiss-Prot : 76 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 Hydroxylation-Deficient Rickets, Type 1a

Diseases in the Vitamin D Hydroxylation-Deficient Rickets, Type 1a family:

Vitamin D Hydroxylation-Deficient Rickets, Type 1b

Diseases related to Vitamin D Hydroxylation-Deficient Rickets, Type 1a via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 hypocalcemic vitamin d-dependent rickets 11.5
2 vitamin d-dependent rickets, type 2a 11.1
3 vitamin d-dependent rickets, type 2b, with normal vitamin d receptor 11.1
4 rickets 10.3
5 hypophosphatemic rickets, x-linked dominant 10.2
6 hypophosphatemia 10.2
7 respiratory failure 10.2
8 secondary hyperparathyroidism 10.2
9 hyperparathyroidism 10.2
10 hypotonia 10.2
11 cerebrotendinous xanthomatosis 10.2
12 xanthomatosis 10.2

Graphical network of the top 20 diseases related to Vitamin D Hydroxylation-Deficient Rickets, Type 1a:



Diseases related to Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Symptoms & Phenotypes for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Human phenotypes related to Vitamin D Hydroxylation-Deficient Rickets, Type 1a:

33 (show all 39)
# Description HPO Frequency HPO Source Accession
1 frontal bossing 33 HP:0002007
2 muscular hypotonia 33 HP:0001252
3 failure to thrive 33 HP:0001508
4 hypophosphatemia 33 HP:0002148
5 rickets 33 HP:0002748
6 abdominal wall muscle weakness 33 HP:0009023
7 irritability 33 HP:0000737
8 delayed eruption of teeth 33 HP:0000684
9 growth delay 33 HP:0001510
10 motor delay 33 HP:0001270
11 recurrent fractures 33 HP:0002757
12 flat occiput 33 HP:0005469
13 elevated circulating parathyroid hormone level 33 HP:0003165
14 difficulty walking 33 HP:0002355
15 bone pain 33 HP:0002653
16 generalized hypotonia 33 HP:0001290
17 femoral bowing 33 HP:0002980
18 elevated alkaline phosphatase 33 HP:0003155
19 tibial bowing 33 HP:0002982
20 bowing of the legs 33 HP:0002979
21 hypoplasia of dental enamel 33 HP:0006297
22 widely patent fontanelles and sutures 33 HP:0004492
23 secondary hyperparathyroidism 33 HP:0000867
24 protuberant abdomen 33 HP:0001538
25 hypocalcemic seizures 33 HP:0002199
26 difficulty standing 33 HP:0003698
27 delayed epiphyseal ossification 33 HP:0002663
28 thin bony cortex 33 HP:0002753
29 fibular bowing 33 HP:0010502
30 generalized aminoaciduria 33 HP:0002909
31 sparse bone trabeculae 33 HP:0002752
32 bulging epiphyses 33 HP:0003013
33 enlargement of the wrists 33 HP:0003020
34 metaphyseal irregularity 33 HP:0003025
35 enlargement of the ankles 33 HP:0003029
36 enlargement of the costochondral junction 33 HP:0000920
37 deformed rib cage 33 HP:0000886
38 bulging of the costochondral junction 33 HP:0000893
39 subperiosteal bone resorption 33 HP:0003106

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Head:
frontal bossing

Growth Other:
failure to thrive
growth retardation
poor growth

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

Skeletal Limbs:
bowing of the legs
enlargement of the wrists
enlargement of the ankles
delayed opacification of the epiphyses
widened, distorted epiphyses
more
Neurologic Central Nervous System:
delayed motor development
seizures due to hypocalcemia

Skeletal Skull:
widened cranial sutures
posterior flattening of the skull

Abdomen External Features:
protuberant abdomen due to muscle weakness

Muscle Soft Tissue:
muscle weakness
difficulty walking
difficulty standing
hypotonia

Laboratory Abnormalities:
hypophosphatemia
hypocalcemia
generalized aminoaciduria
increased serum alkaline phosphatase
increased serum parathyroid hormone (pth)
more
Neurologic Behavioral Psychiatric Manifestations:
irritability

Endocrine Features:
secondary hyperparathyroidism

Head And Neck Teeth:
delayed tooth eruption
enamel hypoplasia

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

Clinical features from OMIM:

264700

UMLS symptoms related to Vitamin D Hydroxylation-Deficient Rickets, Type 1a:


muscle weakness, bone pain, difficulty standing

Drugs & Therapeutics for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Drugs for Vitamin D Hydroxylation-Deficient Rickets, Type 1a (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Parathyroid hormone Approved, Investigational Not Applicable 9002-64-6
2
Teriparatide Approved, Investigational Not Applicable 52232-67-4 16133850
3
Vitamin D Approved, Nutraceutical, Vet_approved Not Applicable 1406-16-2
4
Calcifediol Approved, Nutraceutical Not Applicable 19356-17-3 5283731 6433735
5
Calcium Approved, Nutraceutical Not Applicable 7440-70-2 271
6
Ergocalciferol Approved, Nutraceutical Not Applicable 50-14-6 5280793
7 Calciferol Not Applicable
8 Vitamins Not Applicable
9 Bone Density Conservation Agents Not Applicable
10 Ergocalciferols Not Applicable
11 Hormones Not Applicable
12 Micronutrients Not Applicable
13 Hydroxycholecalciferols Not Applicable
14 Nutrients Not Applicable
15 Calcium, Dietary Not Applicable
16 Trace Elements Not Applicable
17 Vitamin D2 Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Suspected Deficient Activation of Vitamin D in Patients With Secondary Hyperparathyroidism Completed NCT00754442 Not Applicable Teriparatide

Search NIH Clinical Center for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Genetic Tests for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Anatomical Context for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

MalaCards organs/tissues related to Vitamin D Hydroxylation-Deficient Rickets, Type 1a:

42
Kidney, Bone, Cortex

Publications for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Articles related to Vitamin D Hydroxylation-Deficient Rickets, Type 1a:

(show all 18)
# Title Authors Year
1
Genetic and Clinical Characteristics of Patients with Vitamin D Dependent Rickets Type 1A ( 30282619 )
2019
2
Craniofacial and dental characteristics of patients with vitamin-D-dependent rickets type 1A compared to controls and patients with X-linked hypophosphatemia. ( 28608052 )
2018
3
Acute respiratory failure and generalized hypotonia secondary to vitamin D dependent rickets type 1A. ( 30805538 )
2018
4
A Case of Vitamin-D-Dependent Rickets Type 1A with Normal 1,25-Dihydroxyvitamin D Caused by Two Novel Mutations of the CYP27B1 Gene. ( 27287609 )
2017
5
Long-term clinical outcome and the identification of homozygous CYP27B1 gene mutations in a patient with vitamin D hydroxylation-deficient rickets type 1A. ( 27777911 )
2016
6
A Case of Vitamin D-Dependent Rickets Type 1A with a Novel Mutation in the Uzbek Population. ( 27353739 )
2016
7
Urinary calcium to creatinine ratio: a potential marker of secondary hyperparathyroidism in patients with vitamin D-dependent rickets type 1A. ( 25284246 )
2015
8
Novel CYP27B1 Gene Mutations in Patients with Vitamin D-Dependent Rickets Type 1A. ( 26132292 )
2015
9
A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A. ( 24197768 )
2014
10
No evidence of association between mutant alleles of the CYP27B1 gene and multiple sclerosis. ( 23444327 )
2013
11
No evidence for a role of rare CYP27B1 functional variations in multiple sclerosis. ( 23483640 )
2013
12
Clinical and genetic analysis of patients with vitamin D-dependent rickets type 1A. ( 22443290 )
2012
13
Rare variants in the CYP27B1 gene are associated with multiple sclerosis. ( 22190362 )
2011
14
Novel gene mutations in patients with 1alpha-hydroxylase deficiency that confer partial enzyme activity in vitro. ( 12050193 )
2002
15
No enzyme activity of 25-hydroxyvitamin D3 1alpha-hydroxylase gene product in pseudovitamin D deficiency rickets, including that with mild clinical manifestation. ( 10566658 )
1999
16
Inactivating mutations in the 25-hydroxyvitamin D3 1alpha-hydroxylase gene in patients with pseudovitamin D-deficiency rickets. ( 9486994 )
1998
17
Genetics of vitamin D 1alpha-hydroxylase deficiency in 17 families. ( 9837822 )
1998
18
Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. ( 9415400 )
1997

Variations for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

UniProtKB/Swiss-Prot genetic disease variations for Vitamin D Hydroxylation-Deficient Rickets, Type 1a:

76 (show all 18)
# 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 rs568165874
16 CYP27B1 p.Arg453Cys VAR_016972 rs767480544
17 CYP27B1 p.Val478Gly VAR_016973
18 CYP27B1 p.Pro497Arg VAR_016974 rs116179903

ClinVar genetic disease variations for Vitamin D Hydroxylation-Deficient Rickets, Type 1a:

6 (show all 35)
# Gene Variation Type Significance SNP ID Assembly Location
1 CYP27B1 NM_000785.3(CYP27B1): c.320G> A (p.Arg107His) single nucleotide variant Likely pathogenic rs28934604 GRCh37 Chromosome 12, 58159856: 58159856
2 CYP27B1 NM_000785.3(CYP27B1): c.320G> A (p.Arg107His) single nucleotide variant Likely pathogenic rs28934604 GRCh38 Chromosome 12, 57766073: 57766073
3 CYP27B1 NM_000785.3(CYP27B1): c.374G> A (p.Gly125Glu) single nucleotide variant Pathogenic rs28934605 GRCh37 Chromosome 12, 58159802: 58159802
4 CYP27B1 NM_000785.3(CYP27B1): c.374G> A (p.Gly125Glu) single nucleotide variant Pathogenic rs28934605 GRCh38 Chromosome 12, 57766019: 57766019
5 CYP27B1 NM_000785.3(CYP27B1): c.1004G> C (p.Arg335Pro) single nucleotide variant Pathogenic rs28934606 GRCh37 Chromosome 12, 58158293: 58158293
6 CYP27B1 NM_000785.3(CYP27B1): c.1004G> C (p.Arg335Pro) single nucleotide variant Pathogenic rs28934606 GRCh38 Chromosome 12, 57764510: 57764510
7 CYP27B1 NM_000785.3(CYP27B1): c.1144C> T (p.Pro382Ser) single nucleotide variant Pathogenic rs28934607 GRCh37 Chromosome 12, 58157952: 58157952
8 CYP27B1 NM_000785.3(CYP27B1): c.1144C> T (p.Pro382Ser) single nucleotide variant Pathogenic rs28934607 GRCh38 Chromosome 12, 57764169: 57764169
9 CYP27B1 NM_000785.3(CYP27B1): c.630delG (p.Glu211Argfs) deletion Pathogenic rs387906258 GRCh37 Chromosome 12, 58158954: 58158954
10 CYP27B1 NM_000785.3(CYP27B1): c.630delG (p.Glu211Argfs) deletion Pathogenic rs387906258 GRCh38 Chromosome 12, 57765171: 57765171
11 CYP27B1 NM_000785.3(CYP27B1): c.692delC (p.Thr232Argfs) deletion Pathogenic rs387906259 GRCh37 Chromosome 12, 58158892: 58158892
12 CYP27B1 NM_000785.3(CYP27B1): c.692delC (p.Thr232Argfs) deletion Pathogenic rs387906259 GRCh38 Chromosome 12, 57765109: 57765109
13 CYP27B1 NM_000785.3(CYP27B1): c.262delG (p.Val88Trpfs) deletion Pathogenic rs387906260 GRCh37 Chromosome 12, 58159914: 58159914
14 CYP27B1 NM_000785.3(CYP27B1): c.262delG (p.Val88Trpfs) deletion Pathogenic rs387906260 GRCh38 Chromosome 12, 57766131: 57766131
15 CYP27B1 CYP27B1, 7-BP DUP duplication Pathogenic
16 CYP27B1 NM_000785.3(CYP27B1): c.962C> G (p.Thr321Arg) single nucleotide variant Pathogenic rs118204007 GRCh37 Chromosome 12, 58158538: 58158538
17 CYP27B1 NM_000785.3(CYP27B1): c.962C> G (p.Thr321Arg) single nucleotide variant Pathogenic rs118204007 GRCh38 Chromosome 12, 57764755: 57764755
18 CYP27B1 NM_000785.3(CYP27B1): c.589+1G> A single nucleotide variant Pathogenic rs761780097 GRCh37 Chromosome 12, 58159079: 58159079
19 CYP27B1 NM_000785.3(CYP27B1): c.589+1G> A single nucleotide variant Pathogenic rs761780097 GRCh38 Chromosome 12, 57765296: 57765296
20 CYP27B1 NM_000785.3(CYP27B1): c.1226C> T (p.Thr409Ile) single nucleotide variant Pathogenic rs118204008 GRCh37 Chromosome 12, 58157581: 58157581
21 CYP27B1 NM_000785.3(CYP27B1): c.1226C> T (p.Thr409Ile) single nucleotide variant Pathogenic rs118204008 GRCh38 Chromosome 12, 57763798: 57763798
22 CYP27B1 NM_000785.3(CYP27B1): c.1166G> A (p.Arg389His) single nucleotide variant Pathogenic/Likely pathogenic rs118204009 GRCh37 Chromosome 12, 58157930: 58157930
23 CYP27B1 NM_000785.3(CYP27B1): c.1166G> A (p.Arg389His) single nucleotide variant Pathogenic/Likely pathogenic rs118204009 GRCh38 Chromosome 12, 57764147: 57764147
24 CYP27B1 CYP27B1, 5-BP DEL/6-BP INS indel Pathogenic
25 CYP27B1 CYP27B1, IVS2, G-A, +1 single nucleotide variant Pathogenic
26 CYP27B1 NM_000785.3(CYP27B1): c.1165C> G (p.Arg389Gly) single nucleotide variant Pathogenic rs118204010 GRCh37 Chromosome 12, 58157931: 58157931
27 CYP27B1 NM_000785.3(CYP27B1): c.1165C> G (p.Arg389Gly) single nucleotide variant Pathogenic rs118204010 GRCh38 Chromosome 12, 57764148: 57764148
28 CYP27B1 NM_000785.3(CYP27B1): c.1027C> T (p.Leu343Phe) single nucleotide variant Pathogenic rs118204011 GRCh37 Chromosome 12, 58158270: 58158270
29 CYP27B1 NM_000785.3(CYP27B1): c.1027C> T (p.Leu343Phe) single nucleotide variant Pathogenic rs118204011 GRCh38 Chromosome 12, 57764487: 57764487
30 CYP27B1 NM_000785.3(CYP27B1): c.566A> G (p.Glu189Gly) single nucleotide variant Pathogenic rs118204012 GRCh37 Chromosome 12, 58159103: 58159103
31 CYP27B1 NM_000785.3(CYP27B1): c.566A> G (p.Glu189Gly) single nucleotide variant Pathogenic rs118204012 GRCh38 Chromosome 12, 57765320: 57765320
32 CYP27B1 NM_000785.3(CYP27B1): c.305G> A (p.Gly102Glu) single nucleotide variant Pathogenic rs1057520815 GRCh37 Chromosome 12, 58159871: 58159871
33 CYP27B1 NM_000785.3(CYP27B1): c.305G> A (p.Gly102Glu) single nucleotide variant Pathogenic rs1057520815 GRCh38 Chromosome 12, 57766088: 57766088
34 CYP27B1 NM_000785.3(CYP27B1): c.1375C> T (p.Arg459Cys) single nucleotide variant Pathogenic rs555068245 GRCh37 Chromosome 12, 58157432: 58157432
35 CYP27B1 NM_000785.3(CYP27B1): c.1375C> T (p.Arg459Cys) single nucleotide variant Pathogenic rs555068245 GRCh38 Chromosome 12, 57763649: 57763649

Expression for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Search GEO for disease gene expression data for Vitamin D Hydroxylation-Deficient Rickets, Type 1a.

Pathways for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

GO Terms for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Sources for Vitamin D Hydroxylation-Deficient Rickets, Type 1a

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