MCID: HYP260
MIFTS: 47

Hypophosphatemic Rickets, Autosomal Dominant

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

Aliases & Classifications for Hypophosphatemic Rickets, Autosomal Dominant

MalaCards integrated aliases for Hypophosphatemic Rickets, Autosomal Dominant:

Name: Hypophosphatemic Rickets, Autosomal Dominant 57 75 13 55
Autosomal Dominant Hypophosphatemic Rickets 12 59 29 6 15
Adhr 57 59 75
Autosomal Dominant Hypophosphatemia 59 75
Vitamin D-Resistant Rickets, Autosomal Dominant 57
Autosomal Dominant Vitamin D-Resistant Rickets 75
Rickets, Hypophosphatemic, Autosomal Dominant 40
Hypophosphatemia, Autosomal Dominant 57

Characteristics:

Orphanet epidemiological data:

59
autosomal dominant hypophosphatemic rickets
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
highly variable phenotype
incomplete penetrance
two main groups defined by age at onset: childhood (1 to 3 years) and onset after puberty
rarely, patients with childhood-onset may lose the renal phosphate-wasting defect
treatment with vitamin d and phosphate is effective
similar phenotype to x-linked hypophosphatemia (xlh, )


HPO:

32
hypophosphatemic rickets, autosomal dominant:
Onset and clinical course incomplete penetrance
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 57 193100
Disease Ontology 12 DOID:0050948
Orphanet 59 ORPHA89937
UMLS via Orphanet 74 C1704375 C0342642
ICD10 via Orphanet 34 E83.3
MedGen 42 C0342642
MeSH 44 D012279

Summaries for Hypophosphatemic Rickets, Autosomal Dominant

OMIM : 57 Autosomal dominant hypophosphatemic rickets is characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses. In contrast to X-linked dominant hypophosphatemic rickets (XLH; 307800), ADHR shows incomplete penetrance, variable age at onset (childhood to adult), and resolution of the phosphate-wasting defect in rare cases (Econs et al., 1997). See also hypophosphatemic bone disease (146350). (193100)

MalaCards based summary : Hypophosphatemic Rickets, Autosomal Dominant, also known as autosomal dominant hypophosphatemic rickets, is related to tumoral calcinosis, hyperphosphatemic, familial, 1 and osteomalacia. An important gene associated with Hypophosphatemic Rickets, Autosomal Dominant is FGF23 (Fibroblast Growth Factor 23), and among its related pathways/superpathways are Parathyroid hormone synthesis, secretion and action and FGFR3 mutant receptor activation. The drugs Iron and Teriparatide have been mentioned in the context of this disorder. Affiliated tissues include bone and heart, and related phenotypes are muscle weakness and abnormality of the dentition

UniProtKB/Swiss-Prot : 75 Hypophosphatemic rickets, autosomal dominant: A disease characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D3 (calcitriol) levels. Patients frequently present with bone pain, rickets, and tooth abscesses.

Disease Ontology : 12 A rickets characterized by low levels of serum phosphate and elevated levels of ALP and phosphaturia and that has material basis in autosomal dominant inheritance.

Related Diseases for Hypophosphatemic Rickets, Autosomal Dominant

Diseases in the Hereditary Hypophosphatemic Rickets family:

Hypophosphatemic Rickets, Autosomal Dominant Hypophosphatemic Rickets, Autosomal Recessive, 1
Hypophosphatemic Rickets, Autosomal Recessive, 2 Autosomal Recessive Hypophosphatemic Rickets

Diseases related to Hypophosphatemic Rickets, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 26)
# Related Disease Score Top Affiliating Genes
1 tumoral calcinosis, hyperphosphatemic, familial, 1 31.1 FGF23 GALNT3
2 osteomalacia 29.5 FGF23 PHEX SFRP4
3 rickets 29.5 FGF23 PHEX SLC34A3
4 hypophosphatemic rickets, x-linked dominant 28.5 FGF23 PHEX SFRP4 SLC34A3
5 hypophosphatemia 28.4 FGF23 PHEX SFRP4 SLC34A3
6 hypophosphatemic rickets, x-linked recessive 28.3 FGF23 MEPE PHEX SFRP4 SLC34A3
7 tumoral calcinosis, hyperphosphatemic, familial, 2 10.9
8 tumoral calcinosis, hyperphosphatemic, familial, 3 10.9
9 opsismodysplasia 10.3 FGF23 PHEX
10 enthesopathy 10.2 FGF23 PHEX
11 autosomal recessive hypophosphatemic rickets 10.2 FGF23 PHEX
12 bone remodeling disease 10.0 FGF23 PHEX
13 osteogenesis imperfecta, type vi 10.0 MEPE PHEX
14 pulmonary alveolar microlithiasis 9.9 FGF23 SLC34A3
15 hypervitaminosis d 9.8 FGF23 GALNT3
16 hyperparathyroidism 9.7 FGF23 PHEX
17 lacrimoauriculodentodigital syndrome 9.6 FGF23 GALNT3
18 familial tumoral calcinosis 9.4 FGF23 GALNT3 PHEX
19 arterial calcification of infancy 9.4 FGF23 GALNT3 PHEX
20 hyperostosis 9.4 FGF23 GALNT3
21 hyperphosphatemia 9.4 FGF23 GALNT3 PHEX
22 calcinosis 9.4 FGF23 GALNT3 PHEX
23 oncogenic osteomalacia 9.3 FGF23 MEPE PHEX SFRP4
24 phosphorus metabolism disease 8.7 FGF23 GALNT3 PHEX SLC34A3
25 mineral metabolism disease 8.7 FGF23 GALNT3 PHEX SLC34A3
26 hypophosphatemic rickets with hypercalciuria, hereditary 7.6 FGF23 GALNT3 MEPE PHEX SFRP4 SLC34A3

Graphical network of the top 20 diseases related to Hypophosphatemic Rickets, Autosomal Dominant:



Diseases related to Hypophosphatemic Rickets, Autosomal Dominant

Symptoms & Phenotypes for Hypophosphatemic Rickets, Autosomal Dominant

Symptoms via clinical synopsis from OMIM:

57
Laboratory Abnormalities:
hypophosphatemia
increased serum alkaline phosphatase
inappropriately normal serum 1,25-dihydroxyvitamin d3
normocalcemia
normal serum parathyroid hormone (pth)

Genitourinary Kidneys:
renal phosphate wasting
decreased tubular maximum for phosphate reabsorption per glomerular filtration rate (tmp/gfr)

Growth Other:
growth retardation (childhood-onset)

Skeletal Limbs:
lower limb deformities (childhood-onset)
pseudofractures (adult-onset)

Skeletal:
osteomalacia
bone pain
rickets (childhood-onset)

Growth Height:
short stature (in patients with childhood-onset)

Head And Neck Teeth:
tooth abscesses

Muscle Soft Tissue:
generalized weakness (adult-onset)


Clinical features from OMIM:

193100

Human phenotypes related to Hypophosphatemic Rickets, Autosomal Dominant:

59 32 (show all 18)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001324
2 abnormality of the dentition 59 32 occasional (7.5%) Occasional (29-5%) HP:0000164
3 short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0004322
4 hypophosphatemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002148
5 fatigue 59 32 hallmark (90%) Very frequent (99-80%) HP:0012378
6 congestive heart failure 59 32 occasional (7.5%) Occasional (29-5%) HP:0001635
7 abnormal myocardium morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0001637
8 osteomalacia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002749
9 recurrent fractures 59 32 frequent (33%) Frequent (79-30%) HP:0002757
10 spinal canal stenosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003416
11 bone pain 59 32 hallmark (90%) Very frequent (99-80%) HP:0002653
12 abnormality of the respiratory system 59 32 occasional (7.5%) Occasional (29-5%) HP:0002086
13 hyperphosphaturia 59 32 hallmark (90%) Very frequent (99-80%) HP:0003109
14 generalized muscle weakness 32 HP:0003324
15 abnormality of the lower limb 32 HP:0002814
16 elevated alkaline phosphatase 32 HP:0003155
17 hypophosphatemic rickets 32 HP:0004912
18 renal phosphate wasting 32 HP:0000117

MGI Mouse Phenotypes related to Hypophosphatemic Rickets, Autosomal Dominant:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.65 GALNT3 PHEX SFRP4 SLC34A3 FGF23
2 limbs/digits/tail MP:0005371 9.46 FGF23 GALNT3 PHEX SFRP4
3 renal/urinary system MP:0005367 9.35 FGF23 GALNT3 PHEX SFRP4 SLC34A3
4 skeleton MP:0005390 9.1 FGF23 GALNT3 MEPE PHEX SFRP4 SLC34A3

Drugs & Therapeutics for Hypophosphatemic Rickets, Autosomal Dominant

Drugs for Hypophosphatemic Rickets, Autosomal Dominant (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved Not Applicable 7439-89-6 23925
2
Teriparatide Approved, Investigational 52232-67-4 16133850
3
Vitamin D Approved, Nutraceutical, Vet_approved 1406-16-2
4 Ferrous gluconate Not Applicable
5 Hematinics Not Applicable
6 Micronutrients Not Applicable
7 Trace Elements Not Applicable
8 Bone Density Conservation Agents
9 Calcium, Dietary
10 glucocorticoids
11 Vitamins
12 Iron Supplement Nutraceutical Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Iron Therapy for Autosomal Dominant Hypophosphatemic Rickets: A Pilot Project. Recruiting NCT02233322 Not Applicable
2 Study of the Diagnostic Value of Stable Calcium Isotope Profiling in Bone and Calcium Disorders Recruiting NCT02252679
3 FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP) Not yet recruiting NCT03489993

Search NIH Clinical Center for Hypophosphatemic Rickets, Autosomal Dominant

Genetic Tests for Hypophosphatemic Rickets, Autosomal Dominant

Genetic tests related to Hypophosphatemic Rickets, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Autosomal Dominant Hypophosphatemic Rickets 29 FGF23

Anatomical Context for Hypophosphatemic Rickets, Autosomal Dominant

MalaCards organs/tissues related to Hypophosphatemic Rickets, Autosomal Dominant:

41
Bone, Heart

Publications for Hypophosphatemic Rickets, Autosomal Dominant

Articles related to Hypophosphatemic Rickets, Autosomal Dominant:

(show all 17)
# Title Authors Year
1
Iron Supplementation Associated With Loss of Phenotype in Autosomal Dominant Hypophosphatemic Rickets. ( 26186302 )
2015
2
Hip fracture leading to the diagnosis of autosomal dominant hypophosphatemic rickets. A case report. ( 24192443 )
2013
3
Hip fracture leading to the diagnosis of autosomal dominant hypophosphatemic rickets. A case report. ( 23989261 )
2013
4
Autosomal dominant hypophosphatemic rickets in an 85 year old woman: characterization of her disease from infancy through adulthood. ( 23174215 )
2013
5
FGF23 analysis of a Chinese family with autosomal dominant hypophosphatemic rickets. ( 21710177 )
2012
6
Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. ( 22006328 )
2011
7
Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. ( 21880793 )
2011
8
An autosomal dominant hypophosphatemic rickets phenotype in a Tunisian family caused by a new FGF23 missense mutation. ( 19655082 )
2010
9
FGF23 concentrations vary with disease status in autosomal dominant hypophosphatemic rickets. ( 17227222 )
2007
10
[Different forms of clinical presentation of an autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation in one family]. ( 15628294 )
2004
11
The autosomal dominant hypophosphatemic rickets R176Q mutation in fibroblast growth factor 23 resists proteolytic cleavage and enhances in vivo biological potency. ( 12519781 )
2003
12
Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. ( 12130585 )
2002
13
Autosomal-dominant hypophosphatemic rickets (ADHR) mutations stabilize FGF-23. ( 11737582 )
2001
14
Loss of renal phosphate wasting in a child with autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation. ( 11805436 )
2001
15
The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. ( 11157998 )
2001
16
Molecular cloning of a novel human UDP-GalNAc:polypeptide N- acetylgalactosaminyltransferase, GalNAc-T8, and analysis as a candidate autosomal dominant hypophosphatemic rickets (ADHR) gene. ( 10767557 )
2000
17
Autosomal dominant hypophosphatemic rickets/osteomalacia: clinical characterization of a novel renal phosphate-wasting disorder. ( 9024275 )
1997

Variations for Hypophosphatemic Rickets, Autosomal Dominant

UniProtKB/Swiss-Prot genetic disease variations for Hypophosphatemic Rickets, Autosomal Dominant:

75
# Symbol AA change Variation ID SNP ID
1 FGF23 p.Arg176Gln VAR_010717 rs104894347
2 FGF23 p.Arg179Trp VAR_010718 rs28937882
3 FGF23 p.Arg179Gln VAR_010719 rs193922702

ClinVar genetic disease variations for Hypophosphatemic Rickets, Autosomal Dominant:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 FGF23 NM_020638.2(FGF23): c.527G> A (p.Arg176Gln) single nucleotide variant Pathogenic rs104894347 GRCh37 Chromosome 12, 4479738: 4479738
2 FGF23 NM_020638.2(FGF23): c.527G> A (p.Arg176Gln) single nucleotide variant Pathogenic rs104894347 GRCh38 Chromosome 12, 4370572: 4370572
3 FGF23 NM_020638.2(FGF23): c.535C> T (p.Arg179Trp) single nucleotide variant Pathogenic/Likely pathogenic rs28937882 GRCh37 Chromosome 12, 4479730: 4479730
4 FGF23 NM_020638.2(FGF23): c.535C> T (p.Arg179Trp) single nucleotide variant Pathogenic/Likely pathogenic rs28937882 GRCh38 Chromosome 12, 4370564: 4370564
5 FGF23 NM_020638.2(FGF23): c.162G> C (p.Gln54His) single nucleotide variant Likely pathogenic rs193922701 GRCh37 Chromosome 12, 4488587: 4488587
6 FGF23 NM_020638.2(FGF23): c.162G> C (p.Gln54His) single nucleotide variant Likely pathogenic rs193922701 GRCh38 Chromosome 12, 4379421: 4379421
7 FGF23 NM_020638.2(FGF23): c.536G> A (p.Arg179Gln) single nucleotide variant Pathogenic rs193922702 GRCh37 Chromosome 12, 4479729: 4479729
8 FGF23 NM_020638.2(FGF23): c.536G> A (p.Arg179Gln) single nucleotide variant Pathogenic rs193922702 GRCh38 Chromosome 12, 4370563: 4370563

Expression for Hypophosphatemic Rickets, Autosomal Dominant

Search GEO for disease gene expression data for Hypophosphatemic Rickets, Autosomal Dominant.

Pathways for Hypophosphatemic Rickets, Autosomal Dominant

Pathways related to Hypophosphatemic Rickets, Autosomal Dominant according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.98 FGF23 SLC34A3
2
Show member pathways
10.39 FGF23 GALNT3

GO Terms for Hypophosphatemic Rickets, Autosomal Dominant

Biological processes related to Hypophosphatemic Rickets, Autosomal Dominant according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 fibroblast growth factor receptor signaling pathway GO:0008543 9.4 FGF23 GALNT3
2 biomineral tissue development GO:0031214 9.37 MEPE PHEX
3 cellular response to vitamin D GO:0071305 9.32 FGF23 PHEX
4 cellular response to parathyroid hormone stimulus GO:0071374 9.26 FGF23 PHEX
5 cellular phosphate ion homeostasis GO:0030643 9.16 FGF23 SLC34A3
6 phosphate ion homeostasis GO:0055062 8.96 FGF23 SFRP4
7 response to sodium phosphate GO:1904383 8.62 FGF23 PHEX

Sources for Hypophosphatemic Rickets, Autosomal Dominant

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
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44 MeSH
45 MESH via Orphanet
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49 NCI
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51 NDF-RT
54 NINDS
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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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