HOPS
MCID: HYP293
MIFTS: 53

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 58 13 41
Adult Hypophosphatasia 12 60 30 6 15 74
Odontohypophosphatasia 58 60 30 6 74
Hypophosphatasia, Mild 58 56
Hypophosphatasia 76 74
Adult Phosphoethanolaminuria 60
Adult Rathburn Disease 60
Mild Hypophosphatasia 12
Hops 76

Characteristics:

Orphanet epidemiological data:

60
odontohypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;
adult hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;

OMIM:

58
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:

33

Classifications:



External Ids:

Disease Ontology 12 DOID:0110913
OMIM 58 146300
ICD10 via Orphanet 35 E83.3
UMLS via Orphanet 75 C0268413 C1840322

Summaries for Hypophosphatasia, Adult

UniProtKB/Swiss-Prot : 76 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 NAD metabolism and Post-translational modification- synthesis of GPI-anchored proteins. Affiliated tissues include bone and skin, 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 174)
# Related Disease Score Top Affiliating Genes
1 hypophosphatasia, childhood 32.7 ALPL SPTA1
2 hypophosphatasia, infantile 32.2 ALPL ALPP SPTA1
3 hypophosphatasia 30.5 ALPL ALPP ENPP1 SPTA1
4 cleidocranial dysplasia 30.3 ALPL BGLAP
5 chondrocalcinosis 30.3 ALPL ENPP1
6 renal osteodystrophy 30.2 BGLAP PTH
7 osteomalacia 29.9 ALPL BGLAP PTH
8 hypophosphatemia 29.8 BGLAP ENPP1 PTH
9 bone resorption disease 29.7 BGLAP PTH SPP1
10 bone disease 29.4 ALPL ALPP BGLAP PTH SPP1
11 osteoporosis 28.8 ALPL ALPP BGLAP COL1A2 PTH SPP1
12 prenatal benign hypophosphatasia 12.0
13 thyrotoxic periodic paralysis 11.3
14 multiple congenital anomalies-hypotonia-seizures syndrome 3 11.1
15 atelosteogenesis, type i 11.1
16 boomerang dysplasia 11.1
17 dentin dysplasia, type i 11.1
18 hypochondrogenesis 10.3 ALPL SPTA1
19 tick infestation 10.3 ALPL ALPP
20 hypercementosis 10.2 ENPP1 SPP1
21 craniosynostosis 10.2
22 ossification of the posterior longitudinal ligament of spine 10.2 BGLAP ENPP1
23 axial osteomalacia 10.2 BGLAP PTH
24 extraskeletal chondroma 10.2 BGLAP PTH
25 hypophosphatemic rickets with hypercalciuria, hereditary 10.1 ENPP1 PTH
26 osteitis fibrosa 10.1 BGLAP PTH
27 impaired renal function disease 10.1 BGLAP PTH
28 rhabdoid tumor predisposition syndrome 1 10.1 ALPP SPP1
29 intracranial hypertension, idiopathic 10.1
30 osteoporosis, juvenile 10.1 BGLAP PTH
31 cervical squamous cell carcinoma 10.1
32 pancreatic ductal adenocarcinoma 10.1
33 glucocorticoid-induced osteoporosis 10.1 BGLAP PTH
34 secondary hyperparathyroidism of renal origin 10.1 BGLAP PTH
35 papillary cystadenocarcinoma 10.1 BGLAP SPP1
36 dental fluorosis 10.1 BGLAP COL1A2
37 ischemic bone disease 10.1 BGLAP PTH
38 fibrosarcomatous osteosarcoma 10.1 BGLAP SPP1
39 hemarthrosis 10.1 BGLAP SPP1
40 parathyroid gland disease 10.1 BGLAP PTH
41 pseudoxanthoma elasticum 10.1 ALPL ENPP1 SPP1
42 pseudohypoparathyroidism, type ib 10.1 BGLAP PTH
43 osteogenesis imperfecta, type ii 10.1 ALPL COL1A2
44 pseudohypoparathyroidism 10.0 BGLAP PTH
45 osteofibrous dysplasia 10.0 BGLAP SPP1
46 osteomyelitis 10.0
47 hyperparathyroidism 10.0
48 periarthritis 10.0
49 periodontal disease 10.0
50 myopathy 10.0

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



Diseases related to Hypophosphatasia, Adult

Symptoms & Phenotypes for Hypophosphatasia, Adult

Human phenotypes related to Hypophosphatasia, Adult:

33 (show all 11)
# Description HPO Frequency HPO Source Accession
1 carious teeth 33 HP:0000670
2 rickets 33 HP:0002748
3 pathologic fracture 33 HP:0002756
4 abnormality of the foot 33 HP:0001760
5 osteomalacia 33 HP:0002749
6 recurrent fractures 33 HP:0002757
7 chondrocalcinosis 33 HP:0000934
8 premature loss of primary teeth 33 HP:0006323
9 low alkaline phosphatase 33 HP:0003282
10 arthropathy 33 HP:0003040
11 premature loss of permanent teeth 33 HP:0006357

Symptoms via clinical synopsis from OMIM:

58
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

GenomeRNAi Phenotypes related to Hypophosphatasia, Adult according to GeneCards Suite gene sharing:

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased cell migration GR00055-A-1 8.92 ALPG ALPI ALPL ENPP1

MGI Mouse Phenotypes related to Hypophosphatasia, Adult:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 9.76 ALPG ALPI ALPL COL1A2 ENPP1 PTH
2 mortality/aging MP:0010768 9.61 ALPG ALPL COL1A2 DSC3 ENPP1 KHDRBS3
3 skeleton MP:0005390 9.1 ALPL COL1A2 ENPP1 PTH SPP1 SPTA1

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 30 ALPL
2 Odontohypophosphatasia 30

Anatomical Context for Hypophosphatasia, Adult

MalaCards organs/tissues related to Hypophosphatasia, Adult:

42
Bone, Skin

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:

76 (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 14)
# 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.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh38 Chromosome 1, 21573683: 21573683
3 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
4 ALPL NM_000478.5(ALPL): c.979T> C (p.Phe327Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121918010 GRCh38 Chromosome 1, 21573781: 21573781
5 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh38 Chromosome 1, 21564139: 21564139
6 ALPL NM_000478.4(ALPL): c.1133A> T (p.Asp378Val) single nucleotide variant Pathogenic rs121918008 GRCh37 Chromosome 1, 21902361: 21902361
7 ALPL NM_000478.4(ALPL): c.1133A> T (p.Asp378Val) single nucleotide variant Pathogenic rs121918008 GRCh38 Chromosome 1, 21575868: 21575868
8 ALPL NM_000478.5(ALPL): c.979T> C (p.Phe327Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121918010 GRCh37 Chromosome 1, 21900274: 21900274
9 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh37 Chromosome 1, 21889651: 21889651
10 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh38 Chromosome 1, 21563158: 21563158
11 ALPL NM_000478.5(ALPL): c.323C> T (p.Pro108Leu) single nucleotide variant Pathogenic rs121918015 GRCh37 Chromosome 1, 21889628: 21889628
12 ALPL NM_000478.5(ALPL): c.323C> T (p.Pro108Leu) single nucleotide variant Pathogenic rs121918015 GRCh38 Chromosome 1, 21563135: 21563135
13 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Conflicting interpretations of pathogenicity rs121918018 GRCh37 Chromosome 1, 21894694: 21894694
14 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Conflicting interpretations of pathogenicity rs121918018 GRCh38 Chromosome 1, 21568201: 21568201

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 space GO:0005615 9.63 ALPL BGLAP COL1A2 ENPP1 PTH SPP1
2 extracellular region GO:0005576 9.28 ALPG ALPI ALPL BGLAP COL1A2 DSC3
3 anchored component of membrane GO:0031225 9.26 ALPG ALPI ALPL ALPP

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

# Name GO ID Score Top Affiliating Genes
1 dephosphorylation GO:0016311 9.56 ALPG ALPI ALPL ALPP
2 osteoblast differentiation GO:0001649 9.5 ALPL BGLAP SPP1
3 skeletal system development GO:0001501 9.46 ALPL BGLAP COL1A2 PTH
4 bone mineralization GO:0030282 9.43 BGLAP PTH
5 odontogenesis GO:0042476 9.4 BGLAP COL1A2
6 regulation of bone mineralization GO:0030500 9.37 BGLAP ENPP1
7 biomineral tissue development GO:0031214 9.26 ALPL BGLAP ENPP1 SPP1
8 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 metal ion binding GO:0046872 9.81 ALPG ALPI ALPL ALPP BGLAP COL1A2
2 calcium ion binding GO:0005509 9.62 BGLAP DSC3 ENPP1 SPTA1
3 catalytic activity GO:0003824 9.56 ALPI ALPL ALPP ENPP1
4 phosphatase activity GO:0016791 9.26 ALPG ALPI ALPL ALPP
5 alkaline phosphatase activity GO:0004035 8.92 ALPG ALPI ALPL ALPP

Sources for Hypophosphatasia, Adult

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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