MCID: HYP293
MIFTS: 48

Hypophosphatasia, Adult

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases, Oral diseases

Aliases & Classifications for Hypophosphatasia, Adult

MalaCards integrated aliases for Hypophosphatasia, Adult:

Name: Hypophosphatasia, Adult 53 13
Adult Hypophosphatasia 12 55 28 14 69
Odontohypophosphatasia 53 55 28 69
Hypophosphatasia, Mild 53 51
Hypophosphatasia 71 69
Adult Phosphoethanolaminuria 55
Adult Rathburn Disease 55
Mild Hypophosphatasia 12
Hops 71

Characteristics:

Orphanet epidemiological data:

55
odontohypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;
adult hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;

OMIM:

53
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
no skeletal abnormalities in odontohypophosphatasia
rickets and premature primary tooth loss occur in childhood
fractures and dental caries and premature secondary tooth loss occur in adulthood
can be asymptomatic


HPO:

31

Classifications:



External Ids:

OMIM 53 146300
Disease Ontology 12 DOID:0110913
UMLS via Orphanet 70 C1840322 C0268413
ICD10 via Orphanet 33 E83.3

Summaries for Hypophosphatasia, Adult

UniProtKB/Swiss-Prot : 71 Hypophosphatasia: A metabolic bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Four forms are distinguished, depending on the age of onset: perinatal, infantile, childhood and adult type. The perinatal form is the most severe and is almost always fatal. The adult form is mild and characterized by recurrent fractures, osteomalacia, rickets, and loss of teeth. Some cases are asymptomatic, while some patients manifest dental features without skeletal manifestations (odontohypophosphatasia).

MalaCards based summary : Hypophosphatasia, Adult, also known as adult hypophosphatasia, is related to hypophosphatasia, infantile and hypophosphatasia, and has symptoms including carious teeth, rickets and pathologic fracture. An important gene associated with Hypophosphatasia, Adult is ALPL (Alkaline Phosphatase, Liver/Bone/Kidney), and among its related pathways/superpathways are Mesenchymal Stem Cell Differentiation Pathways and Lineage-specific Markers and Lung fibrosis. Affiliated tissues include bone.

Disease Ontology : 12 A hypophosphatasia that has material basis in a heterozygous mutation of ALPL on chromosome 1p36.12.

Description from OMIM: 146300

Related Diseases for Hypophosphatasia, Adult

Diseases in the Hypophosphatasia family:

Hypophosphatasia, Adult Hypophosphatasia, Infantile

Diseases related to Hypophosphatasia, Adult via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 88)
# Related Disease Score Top Affiliating Genes
1 hypophosphatasia, infantile 32.2 ALPL SPTA1
2 hypophosphatasia 30.5 ALPL ENPP1 SPTA1
3 thyrotoxic periodic paralysis 11.1
4 lung disease, immunodeficiency, and chromosome breakage syndrome 10.9
5 hypophosphatasia, childhood 10.4 ALPL SPTA1
6 chondrocalcinosis 10.3 ALPL ENPP1
7 hypercementosis 10.2 ENPP1 SPP1
8 hypophosphatemic rickets with hypercalciuria, hereditary 10.1 ENPP1 PTH
9 ossification of the posterior longitudinal ligament of spine 10.1 BGLAP ENPP1
10 axial osteomalacia 10.1 BGLAP PTH
11 extraskeletal chondroma 10.1 BGLAP PTH
12 osseous heteroplasia, progressive 10.1 BGLAP ENPP1
13 impaired renal function disease 10.1 BGLAP PTH
14 papillary cystadenocarcinoma 10.0 BGLAP SPP1
15 pseudohypoparathyroidism, type ib 10.0 BGLAP PTH
16 hemarthrosis 10.0 BGLAP SPP1
17 ischemic bone disease 10.0 BGLAP PTH
18 adamantinoma of long bones 10.0 BGLAP SPP1
19 pancreatic cholera 10.0 CALCA SPTA1
20 pseudoxanthoma elasticum 10.0 ALPL ENPP1 SPP1
21 osteofibrous dysplasia 10.0 BGLAP SPP1
22 paine syndrome 10.0
23 episodic pain syndrome, familial, 1 10.0
24 patellofemoral pain syndrome 10.0
25 pseudohypoparathyroidism 9.9 BGLAP PTH
26 cervical squamous cell carcinoma 9.9
27 pancreatic ductal adenocarcinoma 9.9
28 fibrogenesis imperfecta ossium 9.9 CALCA PTH
29 hypercalcemia, infantile, 1 9.9 CALCA PTH
30 cloacogenic carcinoma 9.9 CALCA PTH
31 metaphyseal chondrodysplasia, jansen type 9.9 CALCA PTH
32 squamous cell carcinoma 9.9
33 neuronitis 9.9
34 osteonecrosis 9.9 BGLAP PTH
35 bone giant cell tumor 9.9 CALCA SPP1
36 parathyroid carcinoma 9.8 CALCA PTH
37 multiple endocrine neoplasia, type iia 9.8 CALCA PTH
38 osteochondrodysplasia 9.8 ALPL BGLAP
39 hypophosphatemia 9.8 BGLAP ENPP1 PTH
40 root resorption 9.8 CALCA SPP1
41 osteoporosis, juvenile 9.8 BGLAP CALCA
42 hypoparathyroidism 9.8 BGLAP PTH
43 nontoxic goiter 9.8 BGLAP CALCA
44 thyroid gland disease 9.8 CALCA PTH
45 alzheimer disease 9.7
46 colorectal cancer 9.7
47 lung cancer 9.7
48 aging 9.7
49 hepatitis c virus 9.7
50 gastric cancer 9.7

Graphical network of the top 20 diseases related to Hypophosphatasia, Adult:



Diseases related to Hypophosphatasia, Adult

Symptoms & Phenotypes for Hypophosphatasia, Adult

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Teeth:
premature loss of primary teeth
severe dental caries
premature loss of secondary teeth
decreased alveolar bone
enlarged pulp chamber

Skeletal Limbs:
rickets (hypophosphatasia only)
long bone pseudofractures (hypophosphatasia only)
calcium pyrophosphate arthropathy (hypophosphatasia only)
chondrocalcinosis (hypophosphatasia only)

Laboratory Abnormalities:
decreased serum alkaline phosphatase
elevated urinary phosphoethanolamine

Skeletal:
recurrent fractures (hypophosphatasia only)
pathologic fractures (hypophosphatasia only)
osteomalacia (hypophosphatasia only)

Skeletal Feet:
metatarsal stress fracture (hypophosphatasia only)


Clinical features from OMIM:

146300

Human phenotypes related to Hypophosphatasia, Adult:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 carious teeth 31 HP:0000670
2 rickets 31 HP:0002748
3 pathologic fracture 31 HP:0002756
4 abnormality of the foot 31 HP:0001760
5 osteomalacia 31 HP:0002749
6 recurrent fractures 31 HP:0002757
7 chondrocalcinosis 31 HP:0000934
8 premature loss of primary teeth 31 HP:0006323
9 low alkaline phosphatase 31 HP:0003282
10 premature loss of permanent teeth 31 HP:0006357

Drugs & Therapeutics for Hypophosphatasia, Adult

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Hypophosphatasia, Adult

Genetic Tests for Hypophosphatasia, Adult

Genetic tests related to Hypophosphatasia, Adult:

# Genetic test Affiliating Genes
1 Adult Hypophosphatasia 28 ALPL
2 Odontohypophosphatasia 28

Anatomical Context for Hypophosphatasia, Adult

MalaCards organs/tissues related to Hypophosphatasia, Adult:

38
Bone

Publications for Hypophosphatasia, Adult

Articles related to Hypophosphatasia, Adult:

(show all 35)
# Title Authors Year
1
Atypical femur fractures: a distinctive tract of adult hypophosphatasia. ( 29354161 )
2017
2
Adult hypophosphatasia. ( 29405936 )
2017
3
Clinical, radiographic and biochemical characteristics of adult hypophosphatasia. ( 28547134 )
2017
4
Adult hypophosphatasia. ( 26962706 )
2016
5
Recognizing the clinical triad and dural calcification in adult hypophosphatasia. ( 27994097 )
2016
6
ADULT HYPOPHOSPHATASIA TREATED WITH TERIPARATIDE: REPORT OF TWO PATIENTS AND REVIEW OF THE LITERATURE. ( 27042741 )
2016
7
Adult hypophosphatasia with painful periarticular calcification treated with surgical resection. ( 22167380 )
2012
8
Failure of teriparatide in treatment of bone complications of adult hypophosphatasia. ( 22218563 )
2012
9
"Atypical femoral fractures" during bisphosphonate exposure in adult hypophosphatasia. ( 24134968 )
2012
10
"Atypical femoral fractures" during bisphosphonate exposure in adult hypophosphatasia. ( 22322541 )
2012
11
Skeletal mineralization defects in adult hypophosphatasia--a clinical and histological analysis. ( 21267545 )
2011
12
Lack of sustained response to teriparatide in a patient with adult hypophosphatasia. ( 20089612 )
2010
13
Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia. ( 20739387 )
2010
14
Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. ( 19113923 )
2009
15
Teriparatide treatment in adult hypophosphatasia in a patient exposed to bisphosphonate: a case report. ( 22461258 )
2009
16
Treatment of adult hypophosphatasia with teriparatide. ( 18308659 )
2008
17
Intramedullary nailing for adult hypophosphatasia: a case report. ( 19126913 )
2008
18
Novel mouse model of autosomal semidominant adult hypophosphatasia has a splice site mutation in the tissue nonspecific alkaline phosphatase gene Akp2. ( 17539739 )
2007
19
Adult hypophosphatasia treated with teriparatide. ( 17213282 )
2007
20
Adult hypophosphatasia and a low level of red blood cell thiamine pyrophosphate. ( 15802905 )
2005
21
Adult hypophosphatasia. Current aspects. ( 11324927 )
2001
22
Adult hypophosphatasia in an aged patient. ( 9272313 )
1997
23
Adult hypophosphatasia in a geriatric patient. ( 3339218 )
1988
24
Management of femoral fractures and pseudofractures in adult hypophosphatasia. ( 3745261 )
1986
25
Adult hypophosphatasia without apparent skeletal disease: "odontohypophosphatasia" in four heterozygote members of a family. ( 6727276 )
1984
26
Adult hypophosphatasia. ( 6648620 )
1983
27
Adult hypophosphatasia: generalized deficiency of alkaline phosphatase activity demonstrated with cultured skin fibroblasts. ( 7182980 )
1982
28
Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred. ( 7072744 )
1982
29
Heterogeneity of adult hypophosphatasia. Report of severe and mild cases. ( 7235780 )
1981
30
Hypophosphatasia (adult form): quantitation of serum alkaline phosphatase isoenzyme activity in a large kindred. ( 7379306 )
1980
31
Orthopaedic problems in adult hypophosphatasia: a report of two cases. ( 422640 )
1979
32
Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature. ( 481194 )
1979
33
Adult hypophosphatasia dominant inheritance in a large kindred. ( 754388 )
1978
34
Adult hypophosphatasia. ( 167553 )
1975
35
Metabolic observations in adult hypophosphatasia. ( 13798349 )
1960

Variations for Hypophosphatasia, Adult

UniProtKB/Swiss-Prot genetic disease variations for Hypophosphatasia, Adult:

71 (show top 50) (show all 99)
# Symbol AA change Variation ID SNP ID
1 ALPL p.Ala33Val VAR_006147 rs121918005
2 ALPL p.Met62Leu VAR_006148
3 ALPL p.Arg71Cys VAR_006149 rs121918001
4 ALPL p.Arg71Pro VAR_006150 rs121918003
5 ALPL p.Ala111Thr VAR_006151 rs773257111
6 ALPL p.Arg136His VAR_006152 rs121918011
7 ALPL p.Gly162Val VAR_006153 rs121918012
8 ALPL p.His171Tyr VAR_006154
9 ALPL p.Ala177Thr VAR_006155 rs199669988
10 ALPL p.Ala179Thr VAR_006156 rs121918000
11 ALPL p.Glu191Gly VAR_006157
12 ALPL p.Glu191Lys VAR_006158 rs121918007
13 ALPL p.Cys201Tyr VAR_006159
14 ALPL p.Gln207Pro VAR_006160 rs121918004
15 ALPL p.Leu289Phe VAR_006162
16 ALPL p.Asp294Ala VAR_006163 rs121918002
17 ALPL p.Asp306Val VAR_006164
18 ALPL p.Phe327Leu VAR_006165 rs121918010
19 ALPL p.Gly334Asp VAR_006166 rs121918009
20 ALPL p.Asp378Val VAR_006167 rs121918008
21 ALPL p.Val382Ile VAR_006168 rs771540767
22 ALPL p.Tyr436His VAR_006169 rs121918006
23 ALPL p.Glu476Lys VAR_006170
24 ALPL p.Ala40Val VAR_011081 rs770093969
25 ALPL p.Thr134Asn VAR_011082 rs780583917
26 ALPL p.Ala176Thr VAR_011083 rs121918019
27 ALPL p.Arg246Ser VAR_011085
28 ALPL p.Ala348Thr VAR_011086
29 ALPL p.His381Arg VAR_011087
30 ALPL p.Asp406Gly VAR_011088
31 ALPL p.Arg450His VAR_011090 rs150799088
32 ALPL p.Asn478Ile VAR_011092
33 ALPL p.Cys489Ser VAR_011093
34 ALPL p.Ala132Val VAR_013146
35 ALPL p.Ala51Val VAR_013973
36 ALPL p.Gly63Val VAR_013974
37 ALPL p.Arg71His VAR_013975 rs121918003
38 ALPL p.Gly75Ser VAR_013976
39 ALPL p.Ala116Thr VAR_013977 rs121918013
40 ALPL p.Gly120Arg VAR_013978 rs954135116
41 ALPL p.Gly129Arg VAR_013979
42 ALPL p.Arg152His VAR_013980 rs149344982
43 ALPL p.Asn170Asp VAR_013981
44 ALPL p.Ser181Leu VAR_013982 rs199590449
45 ALPL p.Arg184Trp VAR_013983 rs763159520
46 ALPL p.Asn211Asp VAR_013984
47 ALPL p.Gly220Val VAR_013985
48 ALPL p.Arg223Trp VAR_013986 rs766076920
49 ALPL p.Glu235Gly VAR_013987
50 ALPL p.Gly249Val VAR_013988 rs121918018

ClinVar genetic disease variations for Hypophosphatasia, Adult:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh37 Chromosome 1, 21900176: 21900176
2 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
3 ALPL NM_000478.5(ALPL): c.1133A> T (p.Asp378Val) single nucleotide variant Pathogenic rs121918008 GRCh37 Chromosome 1, 21902361: 21902361
4 ALPL NM_000478.5(ALPL): c.1001G> A (p.Gly334Asp) single nucleotide variant Pathogenic/Likely pathogenic rs121918009 GRCh37 Chromosome 1, 21902229: 21902229
5 ALPL NM_000478.5(ALPL): c.979T> C (p.Phe327Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121918010 GRCh37 Chromosome 1, 21900274: 21900274
6 ALPL NM_000478.5(ALPL): c.1559delT (p.Leu520Argfs) deletion Pathogenic rs387906525 GRCh37 Chromosome 1, 21904125: 21904125
7 ALPL NM_000478.5(ALPL): c.407G> A (p.Arg136His) single nucleotide variant Pathogenic/Likely pathogenic rs121918011 GRCh37 Chromosome 1, 21889712: 21889712
8 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh37 Chromosome 1, 21889651: 21889651
9 ALPL NM_000478.5(ALPL): c.1250A> G (p.Asn417Ser) single nucleotide variant Pathogenic/Likely pathogenic rs121918014 GRCh37 Chromosome 1, 21903075: 21903075
10 ALPL NM_000478.5(ALPL): c.323C> T (p.Pro108Leu) single nucleotide variant Pathogenic rs121918015 GRCh37 Chromosome 1, 21889628: 21889628
11 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Pathogenic rs121918018 GRCh37 Chromosome 1, 21894694: 21894694

Expression for Hypophosphatasia, Adult

Search GEO for disease gene expression data for Hypophosphatasia, Adult.

Pathways for Hypophosphatasia, Adult

GO Terms for Hypophosphatasia, Adult

Cellular components related to Hypophosphatasia, Adult according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.43 ALPL BGLAP CALCA ENPP1 PTH SPP1
2 extracellular space GO:0005615 9.1 ALPL BGLAP CALCA ENPP1 PTH SPP1

Biological processes related to Hypophosphatasia, Adult according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 9.5 ALPL BGLAP PTH
2 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007189 9.49 CALCA PTH
3 response to glucocorticoid GO:0051384 9.48 ALPL BGLAP
4 response to nutrient levels GO:0031667 9.46 BGLAP PTH
5 positive regulation of cAMP biosynthetic process GO:0030819 9.43 CALCA PTH
6 embryo implantation GO:0007566 9.4 CALCA SPP1
7 regulation of bone mineralization GO:0030500 9.37 BGLAP ENPP1
8 osteoblast differentiation GO:0001649 9.33 ALPL BGLAP SPP1
9 positive regulation of ossification GO:0045778 9.26 CALCA PTH
10 biomineral tissue development GO:0031214 9.26 ALPL BGLAP ENPP1 SPP1
11 response to vitamin D GO:0033280 8.92 ALPL BGLAP PTH SPP1

Molecular functions related to Hypophosphatasia, Adult according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 calcium ion binding GO:0005509 8.92 BGLAP DSC3 ENPP1 SPTA1

Sources for Hypophosphatasia, Adult

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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