MCID: HYP293
MIFTS: 48

Hypophosphatasia, Adult

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

Aliases & Classifications for Hypophosphatasia, Adult

MalaCards integrated aliases for Hypophosphatasia, Adult:

Name: Hypophosphatasia, Adult 54 13
Adult Hypophosphatasia 12 56 29 14 69
Odontohypophosphatasia 54 56 29 69
Hypophosphatasia 71 69
Adult Phosphoethanolaminuria 56
Adult Rathburn Disease 56
Mild Hypophosphatasia 12
Hops 71

Characteristics:

Orphanet epidemiological data:

56
odontohypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;
adult hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Adult;

OMIM:

54
Inheritance:
autosomal dominant
autosomal recessive

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:



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 thyrotoxic periodic paralysis, and has symptoms including premature loss of permanent teeth, recurrent fractures and osteomalacia. 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. The drugs Antibodies and Immunoglobulins have been mentioned in the context of this disorder. 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, Infantile Hypophosphatasia, Adult

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

(show top 50) (show all 86)
id Related Disease Score Top Affiliating Genes
1 hypophosphatasia, infantile 32.1 ALPL SPTA1
2 thyrotoxic periodic paralysis 11.0
3 lung disease, immunodeficiency, and chromosome breakage syndrome 10.8
4 hypophosphatasia, childhood 10.6 ALPL SPTA1
5 listeria meningitis 10.4 ALPL ENPP1
6 macrotrabecular hepatoblastoma 10.3 ENPP1 SPP1
7 acute frontal sinusitis 10.2 ALPL ENPP1 SPTA1
8 achondrogenesis 10.2 BGLAP PTH
9 ectopic cushing syndrome 10.2 BGLAP ENPP1
10 photoallergic dermatitis 10.2 BGLAP PTH
11 white sponge nevus of cannon, krt4-related 10.2 BGLAP PTH
12 acth-independent macronodular adrenal hyperplasia 10.2 BGLAP ENPP1
13 charcot-marie-tooth disease, type 4k 10.2 ENPP1 PTH
14 hypophosphatasia 10.2
15 prediabetes syndrome 10.2 BGLAP PTH
16 obesity, severe bmiq9 10.1 BGLAP PTH
17 papillary carcinoma 10.1 BGLAP SPP1
18 glomangiomyoma 10.1 BGLAP SPP1
19 bone resorption disease 10.1 BGLAP PTH
20 iris mixed cell melanoma 10.1 CALCA SPTA1
21 pseudoxanthoma elasticum, forme fruste 10.0 ALPL ENPP1 SPP1
22 mitochondrial myopathy with lactic acidosis 10.0 BGLAP SPP1
23 mutism 10.0 BGLAP PTH
24 hypochondrogenesis 10.0 CALCA PTH
25 waardenburg syndrome, type 4b 10.0 CALCA PTH
26 vulvovaginitis 9.9 ALPL BGLAP
27 anal canal squamous cell carcinoma 9.9 CALCA PTH
28 polyglucosan body disease, adult form 9.9 CALCA PTH
29 ovarian insufficiency, familial 9.9 BGLAP PTH
30 polyradiculoneuropathy 9.9 CALCA SPP1
31 patellofemoral pain syndrome 9.9
32 parathyroid carcinoma 9.8 CALCA PTH
33 multiple endocrine neoplasia iib 9.8 CALCA PTH
34 cervical squamous cell carcinoma 9.8
35 pancreatic ductal adenocarcinoma 9.8
36 commensal bacterial infectious disease 9.8 BGLAP ENPP1 PTH
37 glossitis 9.8 CALCA SPP1
38 endemic goiter 9.8 BGLAP CALCA
39 fibrolamellar carcinoma 9.8 CALCA PTH
40 squamous cell carcinoma 9.8
41 neuronitis 9.8
42 phacolytic glaucoma 9.8 BGLAP CALCA
43 parathyroid gland disease 9.7 BGLAP PTH
44 leukemia 9.7
45 small cell cancer of the lung, somatic 9.7 BGLAP PTH SPP1
46 worth's syndrome 9.6 BGLAP CALCA
47 oral squamous cell carcinoma 9.6
48 lung cancer 9.6
49 hepatitis c virus 9.6
50 breast cancer 9.6

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:

54

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)

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)


Clinical features from OMIM:

146300

Human phenotypes related to Hypophosphatasia, Adult:

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

Drugs & Therapeutics for Hypophosphatasia, Adult

Drugs for Hypophosphatasia, Adult (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Antibodies Phase 4,Phase 2,Phase 1
2 Immunoglobulins Phase 4,Phase 2,Phase 1

Interventional clinical trials:

(show all 16)

id Name Status NCT ID Phase Drugs
1 Post-approval Clinical Study of Asfotase Alfa Treatment for Patients With Hypophosphatasia (HPP) in Japan Completed NCT02531867 Phase 4
2 Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP) Completed NCT01163149 Phase 2 asfotase alfa;asfotase alfa
3 Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP) Completed NCT01406977 Phase 2 BPS804
4 Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP) Completed NCT02797821 Phase 2 Asfotase alfa
5 Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP) Completed NCT02456038 Phase 2 Asfotase Alfa (ALXN1215)
6 Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP) Completed NCT00739505 Phase 1
7 Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP) Approved for marketing NCT02496689
8 Burden of Disease in Hypophosphatasia (HPP) Completed NCT02291497
9 A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP) Completed NCT01419028
10 Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP) Completed NCT02104219
11 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168
12 Natural History Study of Patients With Hypophosphatasia (HPP) Recruiting NCT02237625
13 Biomarker for Hypophosphatasia Disease Recruiting NCT02603042
14 An Observational, Longitudinal, Prospective, Long-Term Registry Of Patients With Hypophosphatasia (HPP) Enrolling by invitation NCT02306720
15 Characterisation of Adult-Onset Hypophosphatasia Not yet recruiting NCT02796885
16 Health Burden of Hypophosphatasia Not yet recruiting NCT02751801

Search NIH Clinical Center for Hypophosphatasia, Adult

Genetic Tests for Hypophosphatasia, Adult

Genetic tests related to Hypophosphatasia, Adult:

id Genetic test Affiliating Genes
1 Adult Hypophosphatasia 29
2 Odontohypophosphatasia 29

Anatomical Context for Hypophosphatasia, Adult

MalaCards organs/tissues related to Hypophosphatasia, Adult:

39
Bone

Publications for Hypophosphatasia, Adult

Articles related to Hypophosphatasia, Adult:

id Title Authors Year
1
Hypophosphatasia (adult form): quantitation of serum alkaline phosphatase isoenzyme activity in a large kindred. ( 7379306 )
1980

Variations for Hypophosphatasia, Adult

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

71 (show top 50) (show all 99)
id 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
38 ALPL p.Gly75Ser VAR_013976
39 ALPL p.Ala116Thr VAR_013977 rs121918013
40 ALPL p.Gly120Arg VAR_013978
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)
id 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:

id 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)
id Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 9.5 ALPL BGLAP PTH
2 response to glucocorticoid GO:0051384 9.49 ALPL BGLAP
3 response to nutrient levels GO:0031667 9.48 BGLAP PTH
4 embryo implantation GO:0007566 9.46 CALCA SPP1
5 positive regulation of cAMP biosynthetic process GO:0030819 9.43 CALCA PTH
6 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007189 9.4 CALCA PTH
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:

id 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
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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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