HOPS
MCID: HYP293
MIFTS: 52

Hypophosphatasia, Adult (HOPS)

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

Aliases & Classifications for Hypophosphatasia, Adult

MalaCards integrated aliases for Hypophosphatasia, Adult:

Name: Hypophosphatasia, Adult 57 13 40
Adult Hypophosphatasia 12 59 29 6 15 73
Odontohypophosphatasia 57 59 29 6 73
Hypophosphatasia, Mild 57 55
Hypophosphatasia 75 73
Adult Phosphoethanolaminuria 59
Adult Rathburn Disease 59
Mild Hypophosphatasia 12
Hops 75

Characteristics:

Orphanet epidemiological data:

59
odontohypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;
adult hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;

OMIM:

57
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:

32

Classifications:



External Ids:

OMIM 57 146300
Disease Ontology 12 DOID:0110913
UMLS via Orphanet 74 C1840322 C0268413
ICD10 via Orphanet 34 E83.3

Summaries for Hypophosphatasia, Adult

UniProtKB/Swiss-Prot : 75 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, childhood and hypophosphatasia, infantile. An important gene associated with Hypophosphatasia, Adult is ALPL (Alkaline Phosphatase, Biomineralization Associated), and among its related pathways/superpathways are Lung fibrosis and Endochondral Ossification. Affiliated tissues include bone, skin and lung, and related phenotypes are carious teeth and rickets

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 163)
# Related Disease Score Top Affiliating Genes
1 hypophosphatasia, childhood 32.4 ALPL SPTA1
2 hypophosphatasia, infantile 32.2 ALPL SPTA1
3 hypophosphatasia 30.6 ALPL ENPP1 SPTA1
4 cleidocranial dysplasia 30.2 ALPL BGLAP
5 chondrocalcinosis 30.0 ALPL ENPP1
6 hyperparathyroidism 29.6 BGLAP CALCA PTH
7 hypophosphatemia 29.6 BGLAP ENPP1 PTH
8 renal osteodystrophy 29.6 BGLAP CALCA PTH
9 osteomalacia 29.3 ALPL BGLAP CALCA PTH
10 bone disease 29.2 ALPL BGLAP CALCA PTH SPP1
11 osteoporosis 29.0 ALPL BGLAP CALCA PTH SPP1
12 bone resorption disease 29.0 BGLAP CALCA PTH SPP1
13 prenatal benign hypophosphatasia 12.0
14 thyrotoxic periodic paralysis 11.3
15 atelosteogenesis, type i 11.0
16 boomerang dysplasia 11.0
17 dentin dysplasia, type i 11.0
18 hypochondrogenesis 10.2 ALPL SPTA1
19 craniosynostosis 10.2
20 intracranial hypertension, idiopathic 10.1
21 cervical squamous cell carcinoma 10.1
22 pancreatic ductal adenocarcinoma 10.1
23 hypercementosis 10.1 ENPP1 SPP1
24 hypophosphatemic rickets with hypercalciuria, hereditary 10.1 ENPP1 PTH
25 ossification of the posterior longitudinal ligament of spine 10.1 BGLAP ENPP1
26 axial osteomalacia 10.1 BGLAP PTH
27 extraskeletal chondroma 10.0 BGLAP PTH
28 osseous heteroplasia, progressive 10.0 BGLAP ENPP1
29 impaired renal function disease 10.0 BGLAP PTH
30 papillary cystadenocarcinoma 10.0 BGLAP SPP1
31 ischemic bone disease 10.0 BGLAP PTH
32 fibrosarcomatous osteosarcoma 10.0 BGLAP SPP1
33 osteomyelitis 10.0
34 periarthritis 10.0
35 periodontal disease 10.0
36 myopathy 10.0
37 periodontitis 10.0
38 hemarthrosis 10.0 BGLAP SPP1
39 patellofemoral pain syndrome 10.0
40 pseudohypoparathyroidism 10.0 BGLAP PTH
41 pancreatic cholera 10.0 CALCA SPTA1
42 pseudohypoparathyroidism, type ib 10.0 BGLAP PTH
43 hypoparathyroidism 10.0 BGLAP PTH
44 osteofibrous dysplasia 10.0 BGLAP SPP1
45 pseudoxanthoma elasticum 10.0 ALPL ENPP1 SPP1
46 thyroid gland disease 10.0 CALCA PTH
47 fibrogenesis imperfecta ossium 10.0 CALCA PTH
48 hypercalcemia, infantile, 1 10.0 CALCA PTH
49 cloacogenic carcinoma 10.0 CALCA PTH
50 brittle bone disorder 9.9

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:

57
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:

32 (show all 11)
# Description HPO Frequency HPO Source Accession
1 carious teeth 32 HP:0000670
2 rickets 32 HP:0002748
3 pathologic fracture 32 HP:0002756
4 abnormality of the foot 32 HP:0001760
5 osteomalacia 32 HP:0002749
6 recurrent fractures 32 HP:0002757
7 chondrocalcinosis 32 HP:0000934
8 premature loss of primary teeth 32 HP:0006323
9 low alkaline phosphatase 32 HP:0003282
10 arthropathy 32 HP:0003040
11 premature loss of permanent teeth 32 HP:0006357

MGI Mouse Phenotypes related to Hypophosphatasia, Adult:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.17 ALPL DSC3 ENPP1 KHDRBS3 PTH SPP1

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 29 ALPL
2 Odontohypophosphatasia 29

Anatomical Context for Hypophosphatasia, Adult

MalaCards organs/tissues related to Hypophosphatasia, Adult:

41
Bone, Skin, Lung, Kidney, Liver, Heart, Thyroid

Publications for Hypophosphatasia, Adult

Articles related to Hypophosphatasia, Adult:

(show all 36)
# Title Authors Year
1
Four Novel Mutations in the <i>ALPL</i> Gene in Chinese patients with Odonto, Childhood and Adult Hypophosphatasia. ( 29724887 )
2018
2
Clinical, radiographic and biochemical characteristics of adult hypophosphatasia. ( 28547134 )
2017
3
Adult hypophosphatasia. ( 29405936 )
2017
4
Atypical femur fractures: a distinctive tract of adult hypophosphatasia. ( 29354161 )
2017
5
Recognizing the clinical triad and dural calcification in adult hypophosphatasia. ( 27994097 )
2016
6
Adult hypophosphatasia. ( 26962706 )
2016
7
ADULT HYPOPHOSPHATASIA TREATED WITH TERIPARATIDE: REPORT OF TWO PATIENTS AND REVIEW OF THE LITERATURE. ( 27042741 )
2016
8
&amp;quot;Atypical femoral fractures&amp;quot; during bisphosphonate exposure in adult hypophosphatasia. ( 24134968 )
2012
9
Adult hypophosphatasia with painful periarticular calcification treated with surgical resection. ( 22167380 )
2012
10
&amp;quot;Atypical femoral fractures&amp;quot; during bisphosphonate exposure in adult hypophosphatasia. ( 22322541 )
2012
11
Failure of teriparatide in treatment of bone complications of adult hypophosphatasia. ( 22218563 )
2012
12
Skeletal mineralization defects in adult hypophosphatasia--a clinical and histological analysis. ( 21267545 )
2011
13
Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia. ( 20739387 )
2010
14
Lack of sustained response to teriparatide in a patient with adult hypophosphatasia. ( 20089612 )
2010
15
Teriparatide treatment in adult hypophosphatasia in a patient exposed to bisphosphonate: a case report. ( 22461258 )
2009
16
Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. ( 19113923 )
2009
17
Treatment of adult hypophosphatasia with teriparatide. ( 18308659 )
2008
18
Intramedullary nailing for adult hypophosphatasia: a case report. ( 19126913 )
2008
19
Novel mouse model of autosomal semidominant adult hypophosphatasia has a splice site mutation in the tissue nonspecific alkaline phosphatase gene Akp2. ( 17539739 )
2007
20
Adult hypophosphatasia treated with teriparatide. ( 17213282 )
2007
21
Adult hypophosphatasia and a low level of red blood cell thiamine pyrophosphate. ( 15802905 )
2005
22
Adult hypophosphatasia. Current aspects. ( 11324927 )
2001
23
Adult hypophosphatasia in an aged patient. ( 9272313 )
1997
24
Adult hypophosphatasia in a geriatric patient. ( 3339218 )
1988
25
Management of femoral fractures and pseudofractures in adult hypophosphatasia. ( 3745261 )
1986
26
Adult hypophosphatasia without apparent skeletal disease: &amp;quot;odontohypophosphatasia&amp;quot; in four heterozygote members of a family. ( 6727276 )
1984
27
Adult hypophosphatasia. ( 6648620 )
1983
28
Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred. ( 7072744 )
1982
29
Adult hypophosphatasia: generalized deficiency of alkaline phosphatase activity demonstrated with cultured skin fibroblasts. ( 7182980 )
1982
30
Heterogeneity of adult hypophosphatasia. Report of severe and mild cases. ( 7235780 )
1981
31
Hypophosphatasia (adult form): quantitation of serum alkaline phosphatase isoenzyme activity in a large kindred. ( 7379306 )
1980
32
Orthopaedic problems in adult hypophosphatasia: a report of two cases. ( 422640 )
1979
33
Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature. ( 481194 )
1979
34
Adult hypophosphatasia dominant inheritance in a large kindred. ( 754388 )
1978
35
Adult hypophosphatasia. ( 167553 )
1975
36
Metabolic observations in adult hypophosphatasia. ( 13798349 )
1960

Variations for Hypophosphatasia, Adult

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

75 (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 rs122314282
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 rs147038926
36 ALPL p.Gly63Val VAR_013974
37 ALPL p.Arg71His VAR_013975 rs121918003
38 ALPL p.Gly75Ser VAR_013976 rs130439444
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 20)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
2 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh37 Chromosome 1, 21900176: 21900176
3 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh38 Chromosome 1, 21573683: 21573683
4 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh38 Chromosome 1, 21563158: 21563158
5 ALPL NM_000478.5(ALPL): c.1250A> G (p.Asn417Ser) single nucleotide variant Likely pathogenic rs121918014 GRCh37 Chromosome 1, 21903075: 21903075
6 ALPL NM_000478.5(ALPL): c.1250A> G (p.Asn417Ser) single nucleotide variant Likely pathogenic rs121918014 GRCh38 Chromosome 1, 21576582: 21576582
7 ALPL NM_000478.5(ALPL): c.323C> T (p.Pro108Leu) single nucleotide variant Pathogenic rs121918015 GRCh37 Chromosome 1, 21889628: 21889628
8 ALPL NM_000478.5(ALPL): c.323C> T (p.Pro108Leu) single nucleotide variant Pathogenic rs121918015 GRCh38 Chromosome 1, 21563135: 21563135
9 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Conflicting interpretations of pathogenicity rs121918018 GRCh37 Chromosome 1, 21894694: 21894694
10 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Conflicting interpretations of pathogenicity rs121918018 GRCh38 Chromosome 1, 21568201: 21568201
11 ALPL NM_000478.5(ALPL): c.188G> T (p.Gly63Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 21561103: 21561103
12 ALPL NM_000478.5(ALPL): c.188G> T (p.Gly63Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 21887596: 21887596
13 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh37 Chromosome 1, 21889651: 21889651
14 ALPL NM_000478.5(ALPL): c.1559delT (p.Leu520Argfs) deletion Pathogenic rs387906525 GRCh38 Chromosome 1, 21577632: 21577632
15 ALPL NM_000478.5(ALPL): c.1559delT (p.Leu520Argfs) deletion Pathogenic rs387906525 GRCh37 Chromosome 1, 21904125: 21904125
16 ALPL NM_000478.5(ALPL): c.979T> C (p.Phe327Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121918010 GRCh38 Chromosome 1, 21573781: 21573781
17 ALPL NM_000478.5(ALPL): c.979T> C (p.Phe327Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121918010 GRCh37 Chromosome 1, 21900274: 21900274
18 ALPL NM_000478.5(ALPL): c.1133A> T (p.Asp378Val) single nucleotide variant Pathogenic rs121918008 GRCh38 Chromosome 1, 21575868: 21575868
19 ALPL NM_000478.5(ALPL): c.1133A> T (p.Asp378Val) single nucleotide variant Pathogenic rs121918008 GRCh37 Chromosome 1, 21902361: 21902361
20 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh38 Chromosome 1, 21564139: 21564139

Expression for Hypophosphatasia, Adult

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

Pathways for Hypophosphatasia, Adult

Pathways related to Hypophosphatasia, Adult according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.17 CALCA SPP1
2 11.07 ALPL ENPP1 PTH SPP1
3 10.99 BGLAP SPP1
4 10.92 BGLAP PTH SPP1
5 10.58 BGLAP CALCA PTH SPP1
6 10.4 BGLAP PTH

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 space GO:0005615 9.43 ALPL BGLAP CALCA ENPP1 PTH SPP1
2 extracellular region GO:0005576 9.17 ALPL BGLAP CALCA DSC3 ENPP1 PTH

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

# Name GO ID Score Top Affiliating Genes
1 response to glucocorticoid GO:0051384 9.48 ALPL BGLAP
2 response to mechanical stimulus GO:0009612 9.46 BGLAP ENPP1
3 response to nutrient levels GO:0031667 9.43 BGLAP PTH
4 skeletal system development GO:0001501 9.43 ALPL BGLAP PTH
5 embryo implantation GO:0007566 9.4 CALCA SPP1
6 bone mineralization GO:0030282 9.37 BGLAP PTH
7 osteoblast differentiation GO:0001649 9.33 ALPL BGLAP SPP1
8 regulation of bone mineralization GO:0030500 9.32 BGLAP ENPP1
9 biomineral tissue development GO:0031214 9.26 ALPL BGLAP ENPP1 SPP1
10 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
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
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
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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