VDDR2A
MCID: VTM027
MIFTS: 53

Vitamin D-Dependent Rickets, Type 2a (VDDR2A)

Categories: Bone diseases, Endocrine diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Vitamin D-Dependent Rickets, Type 2a

MalaCards integrated aliases for Vitamin D-Dependent Rickets, Type 2a:

Name: Vitamin D-Dependent Rickets, Type 2a 57 40 73
Hvdrr 57 59 75 55
Hypocalcemic Vitamin D-Resistant Rickets 57 59 75
Vitamin D-Resistant Rickets with End-Organ Unresponsiveness to 1,25-Dihydroxycholecalciferol 57 75
Generalized Resistance to 1,25-Dihydroxyvitamin D 57 75
Rickets, Hereditary Vitamin D-Resistant 57 73
Rickets, Vitamin D-Resistant, Type Iia 57 13
Vitamin D-Dependent Rickets, Type 2 29 6
Rickets-Alopecia Syndrome 57 75
Pddr Iia 57 75
Vddr2a 57 75
Vitamin D-Dependent Rickets, Type 2a, with or Without Alopecia 57
Vitamin D-Dependent Rickets Type 2a with or Without Alopecia 75
Rickets, Hereditary Vitamin D-Resistant; Hvdrr 57
Hypophosphatemic Rickets, X-Linked Dominant 73
Hereditary Vitamin D-Resistant Rickets 59
Rickets Hereditary Vitamin D-Resistant 75
Pseudovitamin D-Deficiency, Type Iia 57
Vitamin D-Dependent Rickets, Type Ii 55
Generalized 1,25-Dihydroxyvitamin D 57
Vitamin D-Dependent Rickets Type Ii 59
Vitamin D-Resistant Rickets Type Ii 59
Pseudovitamin D-Deficiency Type Iia 75
Familial Hypophosphatemic Rickets 73
Rickets Vitamin D-Dependent 2a 75
Type Iia Rickets 75
Vddr Ii 59
Vdrr Ii 59

Characteristics:

Orphanet epidemiological data:

59
hypocalcemic vitamin d-resistant rickets
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset within first 6 months of life
some patients can be treated with large doses of vitamin d and calcium


HPO:

32
vitamin d-dependent rickets, type 2a:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Vitamin D-Dependent Rickets, Type 2a

OMIM : 57 Vitamin D-dependent rickets type 2A (VDDR2A) is caused by a defect in the vitamin D receptor gene. This defect leads to an increase in the circulating ligand, 1,25-dihydroxyvitamin D3. Most patients have total alopecia in addition to rickets. VDDR2B (600785) is a form of vitamin D-dependent rickets with a phenotype similar to VDDR2A but a normal vitamin D receptor, in which end-organ resistance to vitamin D has been shown to be caused by a nuclear ribonucleoprotein that interferes with the vitamin D receptor-DNA interaction. For a general phenotypic description and discussion of genetic heterogeneity of rickets due to disorders in vitamin D metabolism or action, see vitamin D-dependent rickets type 1A (VDDR1A; 264700). (277440)

MalaCards based summary : Vitamin D-Dependent Rickets, Type 2a, also known as hvdrr, is related to rickets and vitamin d-dependent rickets, type 2b, with normal vitamin d receptor, and has symptoms including muscle weakness, arthralgia and bone pain. An important gene associated with Vitamin D-Dependent Rickets, Type 2a is VDR (Vitamin D Receptor), and among its related pathways/superpathways are Tuberculosis and Parathyroid hormone synthesis, secretion and action. Affiliated tissues include bone, skin and cortex, and related phenotypes are joint dislocation and frontal bossing

UniProtKB/Swiss-Prot : 75 Rickets vitamin D-dependent 2A: A disorder of vitamin D metabolism resulting in severe rickets, hypocalcemia and secondary hyperparathyroidism. Most patients have total alopecia in addition to rickets.

Related Diseases for Vitamin D-Dependent Rickets, Type 2a

Graphical network of the top 20 diseases related to Vitamin D-Dependent Rickets, Type 2a:



Diseases related to Vitamin D-Dependent Rickets, Type 2a

Symptoms & Phenotypes for Vitamin D-Dependent Rickets, Type 2a

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

Skin Nails Hair Skin:
cutaneous 0.5 to 1.0 cm bluish and flesh-colored papules (rarely reported)
cutaneous cysts

Skin Nails Hair Hair:
alopecia, complete, in approximately 75% of patients
alopecia appears within 12 months of age and is permanent
eyelashes may be spared

Muscle Soft Tissue:
muscle weakness
difficulty walking
difficulty standing
hypotonia

Laboratory Abnormalities:
hypophosphatemia
hypocalcemia
increased serum 1,25-dihydroxyvitamin d3
increased serum parathyroid hormone
increased serum alkaline phosphatase
more
Neurologic Behavioral Psychiatric Manifestations:
irritability

Endocrine Features:
secondary hyperparathyroidism

Head And Neck Teeth:
delayed tooth eruption
enamel hypoplasia
dental caries by age 2 years

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

Head And Neck Ears:
deafness, sensorineural, mild (rare)

Skin Nails Hair Skin Histology:
absence of normal hair follicles
follicular remnants in cysts
cysts are similar to those seen in 'atrichia with papular lesions'


Clinical features from OMIM:

277440

Human phenotypes related to Vitamin D-Dependent Rickets, Type 2a:

59 32 (show top 50) (show all 65)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint dislocation 59 32 hallmark (90%) Very frequent (99-80%) HP:0001373
2 frontal bossing 59 32 occasional (7.5%) Occasional (29-5%) HP:0002007
3 genu valgum 59 32 occasional (7.5%) Occasional (29-5%) HP:0002857
4 gait disturbance 59 32 frequent (33%) Frequent (79-30%) HP:0001288
5 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
6 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
7 hypophosphatemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002148
8 abnormality of the metaphysis 59 32 frequent (33%) Frequent (79-30%) HP:0000944
9 abnormality of the thorax 59 32 frequent (33%) Frequent (79-30%) HP:0000765
10 dolichocephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000268
11 abnormal form of the vertebral bodies 59 32 frequent (33%) Frequent (79-30%) HP:0003312
12 abnormality of the hip bone 59 32 frequent (33%) Frequent (79-30%) HP:0003272
13 alopecia 59 32 frequent (33%) Frequent (79-30%) HP:0001596
14 hypocalcemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002901
15 genu varum 59 32 frequent (33%) Frequent (79-30%) HP:0002970
16 nephrolithiasis 59 32 frequent (33%) Frequent (79-30%) HP:0000787
17 hyperparathyroidism 59 32 hallmark (90%) Very frequent (99-80%) HP:0000843
18 osteomalacia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002749
19 recurrent fractures 59 32 hallmark (90%) Very frequent (99-80%) HP:0002757
20 bone pain 59 32 hallmark (90%) Very frequent (99-80%) HP:0002653
21 osteolysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002797
22 bone cyst 59 32 hallmark (90%) Very frequent (99-80%) HP:0012062
23 abnormality of the skin 59 32 frequent (33%) Frequent (79-30%) HP:0000951
24 rough bone trabeculation 59 32 hallmark (90%) Very frequent (99-80%) HP:0100670
25 premature loss of primary teeth 59 32 frequent (33%) Frequent (79-30%) HP:0006323
26 muscular hypotonia 32 HP:0001252
27 failure to thrive 32 HP:0001508
28 abnormality of the dentition 59 Occasional (29-5%)
29 carious teeth 32 HP:0000670
30 rickets 32 HP:0002748
31 abdominal wall muscle weakness 32 HP:0009023
32 irritability 32 HP:0000737
33 delayed eruption of teeth 32 HP:0000684
34 growth delay 32 HP:0001510
35 motor delay 32 HP:0001270
36 flat occiput 32 HP:0005469
37 elevated circulating parathyroid hormone level 32 HP:0003165
38 difficulty walking 32 HP:0002355
39 generalized hypotonia 32 HP:0001290
40 femoral bowing 32 HP:0002980
41 abnormal bone structure 59 Very frequent (99-80%)
42 elevated alkaline phosphatase 32 HP:0003155
43 abnormality of adipose tissue 59 Frequent (79-30%)
44 tibial bowing 32 HP:0002982
45 alopecia universalis 32 HP:0002289
46 bowing of the legs 32 HP:0002979
47 hypoplasia of dental enamel 32 HP:0006297
48 widely patent fontanelles and sutures 32 HP:0004492
49 protuberant abdomen 32 HP:0001538
50 hypocalcemic seizures 32 HP:0002199

UMLS symptoms related to Vitamin D-Dependent Rickets, Type 2a:


muscle weakness, arthralgia, bone pain, difficulty standing

MGI Mouse Phenotypes related to Vitamin D-Dependent Rickets, Type 2a:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.78 CYP27B1 NR1H2 PHEX VDR
2 cardiovascular system MP:0005385 9.76 CYP27B1 NR1H2 PHEX VDR
3 cellular MP:0005384 9.73 CYP27B1 NR1H2 PHEX VDR
4 endocrine/exocrine gland MP:0005379 9.67 CYP27B1 NR1H2 PHEX VDR
5 hematopoietic system MP:0005397 9.62 CYP27B1 NR1H2 PHEX VDR
6 craniofacial MP:0005382 9.58 CYP27B1 PHEX VDR
7 immune system MP:0005387 9.56 CYP27B1 NR1H2 PHEX VDR
8 limbs/digits/tail MP:0005371 9.33 CYP27B1 PHEX VDR
9 renal/urinary system MP:0005367 9.13 CYP27B1 PHEX VDR
10 skeleton MP:0005390 8.92 CYP27B1 NR1H2 PHEX VDR

Drugs & Therapeutics for Vitamin D-Dependent Rickets, Type 2a

Search Clinical Trials , NIH Clinical Center for Vitamin D-Dependent Rickets, Type 2a

Genetic Tests for Vitamin D-Dependent Rickets, Type 2a

Genetic tests related to Vitamin D-Dependent Rickets, Type 2a:

# Genetic test Affiliating Genes
1 Vitamin D-Dependent Rickets, Type 2 29 VDR

Anatomical Context for Vitamin D-Dependent Rickets, Type 2a

MalaCards organs/tissues related to Vitamin D-Dependent Rickets, Type 2a:

41
Bone, Skin, Cortex, Kidney

Publications for Vitamin D-Dependent Rickets, Type 2a

Articles related to Vitamin D-Dependent Rickets, Type 2a:

# Title Authors Year
1
Changes in bone metabolic parameters following oral calcium supplementation in an adult patient with vitamin D-dependent rickets type 2A. ( 28367941 )
2017
2
Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) caused by a VDR mutation: A novel mechanism of dominant inheritance. ( 28377956 )
2015
3
Bullous congenital ichthyosiform erythroderma associated with hypocalcemic vitamin D-resistant rickets. ( 18429807 )
2008
4
Vitamin D receptor polymorphisms in hypocalcemic vitamin D-resistant rickets carriers. ( 17106204 )
2007
5
Calcium and vitamin D metabolism in hypocalcemic vitamin D-resistant rickets carriers. ( 16424674 )
2006
6
Human vitamin D receptor mutations: identification of molecular defects in hypocalcemic vitamin D resistant rickets. ( 2618873 )
1989
7
Clinical features of hereditary resistance to 1,25-dihydroxyvitamin D (hereditary hypocalcemic vitamin D resistant rickets type II). ( 3012981 )
1986

Variations for Vitamin D-Dependent Rickets, Type 2a

UniProtKB/Swiss-Prot genetic disease variations for Vitamin D-Dependent Rickets, Type 2a:

75 (show all 14)
# Symbol AA change Variation ID SNP ID
1 VDR p.Gly33Asp VAR_004656 rs121909790
2 VDR p.His35Gln VAR_004657
3 VDR p.Lys45Glu VAR_004658
4 VDR p.Gly46Asp VAR_004659 rs121909797
5 VDR p.Phe47Ile VAR_004660
6 VDR p.Arg50Gln VAR_004661 rs121909794
7 VDR p.Arg73Gln VAR_004662 rs121909791
8 VDR p.Arg80Gln VAR_004663 rs121909793
9 VDR p.Arg274Leu VAR_004664 rs121909796
10 VDR p.His305Gln VAR_004665 rs121909798
11 VDR p.Ile314Ser VAR_004666 rs121909799
12 VDR p.Arg391Cys VAR_004667 rs121909800
13 VDR p.Val346Met VAR_079326 rs267607169
14 VDR p.Ser360Pro VAR_079327

ClinVar genetic disease variations for Vitamin D-Dependent Rickets, Type 2a:

6 (show all 35)
# Gene Variation Type Significance SNP ID Assembly Location
1 VDR NM_001017535.1(VDR): c.98G> A (p.Gly33Asp) single nucleotide variant Pathogenic rs121909790 GRCh37 Chromosome 12, 48272799: 48272799
2 VDR NM_001017535.1(VDR): c.98G> A (p.Gly33Asp) single nucleotide variant Pathogenic rs121909790 GRCh38 Chromosome 12, 47879016: 47879016
3 VDR NM_001017535.1(VDR): c.218G> A (p.Arg73Gln) single nucleotide variant Uncertain significance rs121909791 GRCh37 Chromosome 12, 48258889: 48258889
4 VDR NM_001017535.1(VDR): c.218G> A (p.Arg73Gln) single nucleotide variant Uncertain significance rs121909791 GRCh38 Chromosome 12, 47865106: 47865106
5 VDR NM_001017535.1(VDR): c.885C> A (p.Tyr295Ter) single nucleotide variant Pathogenic rs121909792 GRCh37 Chromosome 12, 48240462: 48240462
6 VDR NM_001017535.1(VDR): c.885C> A (p.Tyr295Ter) single nucleotide variant Pathogenic rs121909792 GRCh38 Chromosome 12, 47846679: 47846679
7 VDR NM_001017535.1(VDR): c.985G> A (p.Glu329Lys) single nucleotide variant Pathogenic rs121909802 GRCh37 Chromosome 12, 48240157: 48240157
8 VDR NM_001017535.1(VDR): c.985G> A (p.Glu329Lys) single nucleotide variant Pathogenic rs121909802 GRCh38 Chromosome 12, 47846374: 47846374
9 VDR NM_001017535.1(VDR): c.239G> A (p.Arg80Gln) single nucleotide variant Pathogenic rs121909793 GRCh37 Chromosome 12, 48258868: 48258868
10 VDR NM_001017535.1(VDR): c.239G> A (p.Arg80Gln) single nucleotide variant Pathogenic rs121909793 GRCh38 Chromosome 12, 47865085: 47865085
11 VDR NM_001017535.1(VDR): c.149G> A (p.Arg50Gln) single nucleotide variant Pathogenic rs121909794 GRCh37 Chromosome 12, 48258958: 48258958
12 VDR NM_001017535.1(VDR): c.149G> A (p.Arg50Gln) single nucleotide variant Pathogenic rs121909794 GRCh38 Chromosome 12, 47865175: 47865175
13 VDR NM_001017535.1(VDR): c.454C> T (p.Gln152Ter) single nucleotide variant Pathogenic rs121909795 GRCh37 Chromosome 12, 48251295: 48251295
14 VDR NM_001017535.1(VDR): c.454C> T (p.Gln152Ter) single nucleotide variant Pathogenic rs121909795 GRCh38 Chromosome 12, 47857512: 47857512
15 VDR NM_001017535.1(VDR): c.821G> T (p.Arg274Leu) single nucleotide variant Pathogenic rs121909796 GRCh37 Chromosome 12, 48240526: 48240526
16 VDR NM_001017535.1(VDR): c.821G> T (p.Arg274Leu) single nucleotide variant Pathogenic rs121909796 GRCh38 Chromosome 12, 47846743: 47846743
17 VDR NM_001017535.1(VDR): c.137G> A (p.Gly46Asp) single nucleotide variant Pathogenic rs121909797 GRCh37 Chromosome 12, 48272760: 48272760
18 VDR NM_001017535.1(VDR): c.137G> A (p.Gly46Asp) single nucleotide variant Pathogenic rs121909797 GRCh38 Chromosome 12, 47878977: 47878977
19 VDR NM_001017535.1(VDR): c.915C> G (p.His305Gln) single nucleotide variant Pathogenic rs121909798 GRCh37 Chromosome 12, 48240227: 48240227
20 VDR NM_001017535.1(VDR): c.915C> G (p.His305Gln) single nucleotide variant Pathogenic rs121909798 GRCh38 Chromosome 12, 47846444: 47846444
21 VDR NM_001017535.1(VDR): c.941T> G (p.Ile314Ser) single nucleotide variant Pathogenic rs121909799 GRCh37 Chromosome 12, 48240201: 48240201
22 VDR NM_001017535.1(VDR): c.941T> G (p.Ile314Ser) single nucleotide variant Pathogenic rs121909799 GRCh38 Chromosome 12, 47846418: 47846418
23 VDR NM_001017535.1(VDR): c.1171C> T (p.Arg391Cys) single nucleotide variant Pathogenic rs121909800 GRCh37 Chromosome 12, 48238642: 48238642
24 VDR NM_001017535.1(VDR): c.1171C> T (p.Arg391Cys) single nucleotide variant Pathogenic rs121909800 GRCh38 Chromosome 12, 47844859: 47844859
25 VDR NM_001017535.1(VDR): c.88C> T (p.Arg30Ter) single nucleotide variant Pathogenic rs121909801 GRCh37 Chromosome 12, 48272809: 48272809
26 VDR NM_001017535.1(VDR): c.88C> T (p.Arg30Ter) single nucleotide variant Pathogenic rs121909801 GRCh38 Chromosome 12, 47879026: 47879026
27 VDR VDR, 1-BP DEL, 366C deletion Pathogenic
28 VDR NM_001017535.1(VDR): c.1036G> A (p.Val346Met) single nucleotide variant Pathogenic rs267607169 GRCh37 Chromosome 12, 48238777: 48238777
29 VDR NM_001017535.1(VDR): c.1036G> A (p.Val346Met) single nucleotide variant Pathogenic rs267607169 GRCh38 Chromosome 12, 47844994: 47844994
30 PHEX NM_000444.5(PHEX): c.1735G> A (p.Gly579Arg) single nucleotide variant Pathogenic/Likely pathogenic rs875989883 GRCh37 Chromosome X, 22237187: 22237187
31 PHEX NM_000444.5(PHEX): c.1735G> A (p.Gly579Arg) single nucleotide variant Pathogenic/Likely pathogenic rs875989883 GRCh38 Chromosome X, 22219070: 22219070
32 VDR NM_001017535.1(VDR): c.1190A> C (p.His397Pro) single nucleotide variant Pathogenic rs886037890 GRCh37 Chromosome 12, 48238623: 48238623
33 VDR NM_001017535.1(VDR): c.1190A> C (p.His397Pro) single nucleotide variant Pathogenic rs886037890 GRCh38 Chromosome 12, 47844840: 47844840
34 VDR NM_001017535.1(VDR): c.1171C> A (p.Arg391Ser) single nucleotide variant Pathogenic rs121909800 GRCh37 Chromosome 12, 48238642: 48238642
35 VDR NM_001017535.1(VDR): c.1171C> A (p.Arg391Ser) single nucleotide variant Pathogenic rs121909800 GRCh38 Chromosome 12, 47844859: 47844859

Expression for Vitamin D-Dependent Rickets, Type 2a

Search GEO for disease gene expression data for Vitamin D-Dependent Rickets, Type 2a.

Pathways for Vitamin D-Dependent Rickets, Type 2a

Pathways related to Vitamin D-Dependent Rickets, Type 2a according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.62 CYP27B1 VDR
2 11.35 CYP27B1 VDR
3
Show member pathways
11.21 NR1H2 VDR
4 10.81 CYP27B1 VDR
5 10.5 CYP27B1 VDR
6 9.62 CYP27B1 VDR

GO Terms for Vitamin D-Dependent Rickets, Type 2a

Cellular components related to Vitamin D-Dependent Rickets, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor complex GO:0090575 8.62 NR1H2 VDR

Biological processes related to Vitamin D-Dependent Rickets, Type 2a according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 transcription, DNA-templated GO:0006351 9.49 NR1H2 VDR
2 transcription initiation from RNA polymerase II promoter GO:0006367 9.48 NR1H2 VDR
3 skeletal system development GO:0001501 9.46 PHEX VDR
4 calcium ion transport GO:0006816 9.43 CYP27B1 VDR
5 steroid hormone mediated signaling pathway GO:0043401 9.4 NR1H2 VDR
6 bone mineralization GO:0030282 9.37 CYP27B1 PHEX
7 decidualization GO:0046697 9.32 CYP27B1 VDR
8 response to vitamin D GO:0033280 9.26 CYP27B1 PHEX
9 positive regulation of keratinocyte differentiation GO:0045618 9.16 CYP27B1 VDR
10 vitamin D metabolic process GO:0042359 8.96 CYP27B1 VDR
11 positive regulation of vitamin D 24-hydroxylase activity GO:0010980 8.62 CYP27B1 VDR

Molecular functions related to Vitamin D-Dependent Rickets, Type 2a according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.71 CYP27B1 NR1H2 PHEX VDR
2 zinc ion binding GO:0008270 9.54 NR1H2 PHEX VDR
3 signaling receptor activity GO:0038023 9.43 NR1H2 VDR
4 transcription regulatory region sequence-specific DNA binding GO:0000976 9.32 NR1H2 VDR
5 nuclear receptor transcription coactivator activity GO:0030374 9.26 NR1H2 VDR
6 steroid hormone receptor activity GO:0003707 9.16 NR1H2 VDR
7 nuclear receptor activity GO:0004879 8.96 NR1H2 VDR
8 retinoid X receptor binding GO:0046965 8.62 NR1H2 VDR

Sources for Vitamin D-Dependent Rickets, Type 2a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
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32 HPO
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34 ICD10 via Orphanet
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45 MESH via Orphanet
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62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
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74 UMLS via Orphanet
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