MCID: VTM026
MIFTS: 35

Vitamin D Hydroxylation-Deficient Rickets, Type 1a

Categories: 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 57
25-Hydroxycholecalciferol-1-Hydroxylase Deficiency 57 75
Vitamin D-Dependent Rickets, Type 1a 57 40
Vitamin D-Dependent Rickets, Type I 57 13
1-Alpha-Hydroxylase Deficiency 57 75
Pddr Ia 57 75
Vddr1a 57 75
Pddr1a 57 75
Vdd1 57 75
1-Alpha, 25-Hydroxyvitamin D3 Deficiency, Selective 57
Pseudovitamin D-Deficiency Rickets, Type Ia; Pddr1a 57
1-Alpha 25-Hydroxyvitamin D3 Deficiency Selective 75
Pseudovitamin D-Deficiency Rickets, Type Ia 57
Pseudovitamin D-Deficiency Rickets Type Ia 75
Vitamin D-Dependent Rickets, Type 1 73
Vitamin D Dependency, Type 1; Vdd1 57
Pseudovitamin D Deficiency Rickets 75
Rickets Vitamin D-Dependent 1a 75
Vitamin D Dependency, Type 1 57
Vitamin D Dependency Type 1 75
Pddr 75

Characteristics:

OMIM:

57
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 hydroxylation-deficient rickets, type 1a:
Inheritance autosomal recessive inheritance


Classifications:



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

OMIM : 57 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 Teriparatide and Ergocalciferol have been mentioned in the context of this disorder. Affiliated tissues include bone, kidney and liver, and related phenotypes are frontal bossing and muscular hypotonia

UniProtKB/Swiss-Prot : 75 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 1b family:

Vitamin D Hydroxylation-Deficient Rickets, Type 1a

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

# Related Disease Score Top Affiliating Genes
1 hypocalcemic vitamin d-dependent rickets 11.3
2 vitamin d-dependent rickets, type 2a 10.9
3 rickets 10.2

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

Symptoms via clinical synopsis from OMIM:

57
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

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

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

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 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Teriparatide Approved, Investigational Not Applicable 52232-67-4 16133850
2
Ergocalciferol Approved, Nutraceutical Not Applicable 50-14-6 5280793
3
Vitamin D Approved, Nutraceutical, Vet_approved Not Applicable 1406-16-2
4 Bone Density Conservation Agents Not Applicable
5 Calcifediol Not Applicable 19356-17-3
6 Ergocalciferols Not Applicable
7 Hydroxycholecalciferols Not Applicable
8 Micronutrients Not Applicable
9 Trace Elements Not Applicable
10 Vitamins Not Applicable
11 Calciferol Nutraceutical Not Applicable
12 Vitamin D2 Nutraceutical 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:

41
Bone, Kidney, Liver, Cortex

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

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

# Title Authors Year
1
Craniofacial and dental characteristics of patients with vitamin-D-dependent rickets type 1A compared to controls and patients with X-linked hypophosphatemia. ( 28608052 )
2017
2
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
3
The first case of vitamin D dependent rickets type 1A from Uzbek population with a novel mutation. ( 27353739 )
2016
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 )
2016
5
Novel CYP27B1 Gene Mutations in Patients with Vitamin D-Dependent Rickets Type 1A. ( 26132292 )
2015
6
Urinary calcium to creatinine ratio: a potential marker of secondary hyperparathyroidism in patients with vitamin D-dependent rickets type 1A. ( 25284246 )
2014
7
A novel compound mutation of CYP27B1 in a Chinese family with vitamin D-dependent rickets type 1A. ( 24197768 )
2013
8
Clinical and genetic analysis of patients with vitamin D-dependent rickets type 1A. ( 22443290 )
2012

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

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

75 (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

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

6
(show all 37)
# 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.1358G> A (p.Arg453His) single nucleotide variant no interpretation for the single variant rs759208930 GRCh37 Chromosome 12, 58157449: 58157449
33 CYP27B1 NM_000785.3(CYP27B1): c.1358G> A (p.Arg453His) single nucleotide variant no interpretation for the single variant rs759208930 GRCh38 Chromosome 12, 57763666: 57763666
34 CYP27B1 NM_000785.3(CYP27B1): c.1319_1325dupCCCACCC (p.Phe443Profs) duplication Pathogenic rs780950819 GRCh37 Chromosome 12, 58157482: 58157482
35 CYP27B1 NM_000785.3(CYP27B1): c.1319_1325dupCCCACCC (p.Phe443Profs) duplication Pathogenic rs780950819 GRCh38 Chromosome 12, 57763699: 57763705
36 CYP27B1 NM_000785.3(CYP27B1): c.1375C> T (p.Arg459Cys) single nucleotide variant Pathogenic rs555068245 GRCh37 Chromosome 12, 58157432: 58157432
37 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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