HPP
MCID: HYP035
MIFTS: 57

Hypophosphatasia (HPP) malady

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

Aliases & Classifications for Hypophosphatasia

Aliases & Descriptions for Hypophosphatasia:

Name: Hypophosphatasia 12 23 50 24 25 56 29 52 42 14 69
Phosphoethanolaminuria 50 25 56
Deficiency of Alkaline Phosphatase 12 25
Childhood Hypophosphatasia 12 69
Rathburn Disease 50 56
Deficiency of Alkaline Phosphatase [ambiguous] 12
Hypophosphatasia, Childhood 42
Infantile Hypophosphatasia 69
Hypophospatasia, Childhood 12
Phosphoethanol-Aminuria 50
Hypophosphatasia, Mild 52
Hypophosphatasia Mild 50
Hpp 56

Characteristics:

Orphanet epidemiological data:

56
hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (France),1-9/1000000 (United Kingdom),1-9/1000000 (Ireland),1-9/1000000 (Japan); Age of onset: All ages; Age of death: any age;

Classifications:



External Ids:

Disease Ontology 12 DOID:14213
ICD10 33 E83.39
NCIt 47 C26798
Orphanet 56 ORPHA436
MESH via Orphanet 43 D007014
UMLS via Orphanet 70 C0020630
ICD10 via Orphanet 34 E83.3

Summaries for Hypophosphatasia

NIH Rare Diseases : 50 hypophosphatasia (hpp) is a genetic condition that causes abnormal development of the bones and teeth. the severity of hpp can vary widely, from fetal death to fractures that don't begin until adulthood. signs and symptoms may include poor feeding and respiratory problems in infancy; short stature; weak and soft bones; short limbs; other skeletal abnormalities; and hypercalcemia. complications can be life-threatening. the mildest form of the condition, called odontohypophosphatasia, only affects the teeth. hpp is caused by mutations in the alpl gene. perinatal (onset before birth) and infantile hpp are inherited in an autosomal recessive manner. the milder forms, especially adult forms and odontohypophosphatasia, may be inherited in an autosomal recessive or autosomal dominant manner. while treatment has always been symptomatic and supportive, recently an enzyme replacement therapy (ert) called asfotase alfa has been show to improve bone manifestations people with childhood onset hpp and has been approved by the fda. last updated: 2/1/2016

MalaCards based summary : Hypophosphatasia, also known as phosphoethanolaminuria, is related to hypophosphatasia, infantile and hypophosphatasia, adult, and has symptoms including seizures, muscular hypotonia and respiratory insufficiency. An important gene associated with Hypophosphatasia is ALPL (Alkaline Phosphatase, Liver/Bone/Kidney), and among its related pathways/superpathways are NAD metabolism and Mesenchymal Stem Cell Differentiation Pathways and Lineage-specific Markers. The drugs Antibodies and Immunoglobulin G have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and liver, and related phenotypes are cardiovascular system and growth/size/body region

Genetics Home Reference : 25 Hypophosphatasia is an inherited disorder that affects the development of bones and teeth. This condition disrupts a process called mineralization, in which minerals such as calcium and phosphorus are deposited in developing bones and teeth. Mineralization is critical for the formation of bones that are strong and rigid and teeth that can withstand chewing and grinding.

GeneReviews: NBK1150

Related Diseases for Hypophosphatasia

Diseases in the Hypophosphatasia family:

Hypophosphatasia, Infantile Hypophosphatasia, Adult

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

(show top 50) (show all 62)
id Related Disease Score Top Affiliating Genes
1 hypophosphatasia, infantile 33.5 ALPL ALPP SPTA1
2 hypophosphatasia, adult 32.8 ALPL ENPP1 PTH SPP1 SPTA1
3 hypophosphatasia, childhood 31.7 ALPL ALPP ANKH DLX3 DSPP ENPP1
4 prenatal benign hypophosphatasia 11.7
5 pyropoikilocytosis 11.6
6 uterine corpus adenosarcoma 10.2 ALPL ALPP
7 maroteaux stanescu cousin syndrome 10.2 ALPL ALPP
8 diaphragm disease 10.2 ALPP DSPP
9 kidney cortex necrosis 10.2 ALPL ANKH
10 acth-independent macronodular adrenal hyperplasia 10.1 ALPP ENPP1
11 inferior myocardial infarction 10.1 ALPL ALPP
12 tendons, extensor, of fingers, anomalous insertion of 10.1 DLX3 DSPP
13 periodontitis 10.1
14 vulvovaginitis 10.0 ALPL ANKH
15 listeria meningitis 10.0 ALPL ANKH ENPP1
16 childhood parosteal osteogenic sarcoma 10.0 ENPP1 SPP1
17 adermatoglyphia 10.0 DSPP SPP1
18 opportunistic bacterial infectious disease 10.0 DSPP ENPP1 PTH
19 adenosquamous breast carcinoma 10.0 DSPP SPP1
20 diabetic foot ulcers 10.0 DSPP SPP1
21 ovarian malignant mesothelioma 10.0 DLX3 DSPP
22 diabetic neuropathy 9.9 DSPP SPP1
23 glossitis 9.9 DSPP SPP1
24 parathyroid gland disease 9.9 ALPP PTH
25 cleidocranial dysplasia 9.8
26 osteogenesis imperfecta 9.8
27 craniosynostosis 9.8
28 psoriasis 9.8
29 pancreatitis 9.8
30 childhood absence epilepsy 9.8 ANKH ENPP1 SPP1
31 hypotrichosis 8 9.8 ALPP PTH SPP1
32 dysbaric osteonecrosis 9.8 PTH SPP1
33 renal osteodystrophy 9.8
34 hyperparathyroidism 9.8
35 periarthritis 9.8
36 periodontal disease 9.8
37 arthropathy 9.8
38 myopathy 9.8
39 osteomyelitis 9.8
40 arterial calcification, generalized, of infancy, 2 9.7 ALPL ANKH ENPP1 SPP1
41 carnitine deficiency, systemic primary 9.7 ALPL ALPP PTH SPP1
42 band keratopathy 9.6
43 chondrocalcinosis 9.6
44 dwarfism 9.6
45 nephrotic syndrome 9.6
46 endotheliitis 9.6
47 phenylketonuria 9.6
48 chronic recurrent multifocal osteomyelitis 9.6
49 nephrocalcinosis 9.6
50 west syndrome 9.6

Graphical network of the top 20 diseases related to Hypophosphatasia:



Diseases related to Hypophosphatasia

Symptoms & Phenotypes for Hypophosphatasia

Human phenotypes related to Hypophosphatasia:

56 32 (show all 20)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 56 32 Frequent (79-30%) HP:0001250
2 muscular hypotonia 56 32 Frequent (79-30%) HP:0001252
3 respiratory insufficiency 56 32 Frequent (79-30%) HP:0002093
4 bowing of the long bones 56 32 Very frequent (99-80%) HP:0006487
5 abnormality of the teeth 56 32 Very frequent (99-80%) HP:0000164
6 short stature 56 32 Very frequent (99-80%) HP:0004322
7 feeding difficulties in infancy 56 32 Very frequent (99-80%) HP:0008872
8 emphysema 56 32 Very frequent (99-80%) HP:0002097
9 anemia 56 32 Frequent (79-30%) HP:0001903
10 irritability 56 32 Frequent (79-30%) HP:0000737
11 abnormality of the metaphyses 56 32 Very frequent (99-80%) HP:0000944
12 narrow chest 56 32 Very frequent (99-80%) HP:0000774
13 abnormality of the ribs 56 32 Very frequent (99-80%) HP:0000772
14 recurrent fractures 56 32 Frequent (79-30%) HP:0002757
15 hypercalcemia 56 32 Frequent (79-30%) HP:0003072
16 failure to thrive in infancy 56 32 Very frequent (99-80%) HP:0001531
17 large fontanelles 56 32 Very frequent (99-80%) HP:0000239
18 skin dimple over apex of long bone angulation 56 32 Very frequent (99-80%) HP:0001024
19 craniosynostosis 56 32 Very frequent (99-80%) HP:0001363
20 skin dimples 56 Very frequent (99-80%)

UMLS symptoms related to Hypophosphatasia:


seizures, waddling gait, constipation, fever of unknown origin, vomiting

MGI Mouse Phenotypes related to Hypophosphatasia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.87 SPTA1 ALPL ANKH DLX3 ENPP1 PTH
2 growth/size/body region MP:0005378 9.8 ALPL ANKH DLX3 ENPP1 PTH SPP1
3 immune system MP:0005387 9.63 ALPL ANKH ENPP1 PTH SPP1 SPTA1
4 mortality/aging MP:0010768 9.5 ALPL ANKH DLX3 ENPP1 PTH SPP1
5 skeleton MP:0005390 9.1 ALPL ANKH ENPP1 PTH SPP1 SPTA1

Drugs & Therapeutics for Hypophosphatasia

Drugs for Hypophosphatasia (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 Immunoglobulin G Phase 4,Phase 2,Phase 1
3 Immunoglobulins Phase 4,Phase 2,Phase 1

Interventional clinical trials:

(show all 23)
id Name Status NCT ID Phase
1 Post-approval Clinical Study of Asfotase Alfa Treatment for Patients With Hypophosphatasia (HPP) in Japan Completed NCT02531867 Phase 4
2 Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP) Active, not recruiting NCT01176266 Phase 2, Phase 3
3 Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP) Completed NCT01163149 Phase 2
4 Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP) Completed NCT02456038 Phase 2
5 Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP) Completed NCT01406977 Phase 2
6 Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP) Completed NCT01205152 Phase 2
7 Extension Study of Protocol ENB-006-09 - Study of Asfotase Alfa in Children With Hypophosphatasia (HPP) Completed NCT01203826 Phase 2
8 Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP) Completed NCT00744042 Phase 1, Phase 2
9 Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP) Completed NCT00952484 Phase 2
10 Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP) Active, not recruiting NCT02797821 Phase 2
11 Safety and Efficacy Study of ENB-0040 in Juvenile Patients With Hypophosphatasia (HPP) Withdrawn NCT00894075 Phase 2
12 Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP) Completed NCT00739505 Phase 1
13 Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP) Approved for marketing NCT02496689
14 A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP) Completed NCT01419028
15 Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP) Completed NCT02104219
16 Burden of Disease in Hypophosphatasia (HPP) Completed NCT02291497
17 Non-interventional Substudy of ALX-HPP-502 to Assess Natural History of Patients With Juvenile-onset HPP Who Served as Historical Controls in ENB-006-09 Completed NCT02235493
18 Natural History Study of Patients With Hypophosphatasia (HPP) Recruiting NCT02237625
19 Biomarker for Hypophosphatasia Disease Recruiting NCT02603042
20 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168
21 An Observational, Longitudinal, Prospective, Long-Term Registry Of Patients With Hypophosphatasia (HPP) Enrolling by invitation NCT02306720
22 Health Burden of Hypophosphatasia Not yet recruiting NCT02751801
23 Characterisation of Adult-Onset Hypophosphatasia Not yet recruiting NCT02796885

Search NIH Clinical Center for Hypophosphatasia

Cochrane evidence based reviews: hypophosphatasia

Genetic Tests for Hypophosphatasia

Genetic tests related to Hypophosphatasia:

id Genetic test Affiliating Genes
1 Hypophosphatasia 29 24 ALPL

Anatomical Context for Hypophosphatasia

MalaCards organs/tissues related to Hypophosphatasia:

39
Bone, Skin, Liver, Kidney, Bone Marrow, Testes, Neutrophil

Publications for Hypophosphatasia

Articles related to Hypophosphatasia:

(show top 50) (show all 518)
id Title Authors Year
1
Hypophosphatasia: Enzyme Replacement Therapy Brings New Opportunities and New Challenges. ( 28084648 )
2017
2
Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR-based metabolomics analysis. ( 28072448 )
2017
3
A homozygous intronic branch-point deletion in the ALPL gene causes infantile hypophosphatasia. ( 27777120 )
2017
4
Asfotase alfa therapy for children with hypophosphatasia. ( 27699270 )
2016
5
Identification of a molecular defect in a stillborn fetus with perinatal lethal hypophosphatasia using a disease-associated genome sequencing approach. ( 27179278 )
2016
6
Hypophosphatasia: Natural history study of 101 affected children investigated at one research center. ( 27576207 )
2016
7
Glycosylation-deficient mutations in tissue-nonspecific alkaline phosphatase impair its structure and function and are linked to infantile hypophosphatasia. ( 26797772 )
2016
8
Hypophosphatasia and the risk of atypical femur fractures: a case-control study. ( 27507156 )
2016
9
Nondestructive Microcomputed Tomography Evaluation of Mineral Density in Exfoliated Teeth with Hypophosphatasia. ( 27847653 )
2016
10
Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. ( 26893260 )
2016
11
Asfotase Alfa: A Review in Paediatric-Onset Hypophosphatasia. ( 26744272 )
2016
12
Hypophosphatasia. ( 27084188 )
2016
13
Atypical femoral fracture in a 51-year-old woman: Revealing a hypophosphatasia. ( 26992955 )
2016
14
Clinical Images: A Cloudy Skull-Hypophosphatasia as Reason for Copper-Beaten Skull. ( 27780282 )
2016
15
A Diagnostic Algorithm for Children with Low Alkaline Phosphatase Activities: Lessons Learned from Laboratory Screening forA Hypophosphatasia. ( 26896157 )
2016
16
Transformative therapy in hypophosphatasia. ( 26992417 )
2016
17
Physical therapy management of infants and children with hypophosphatasia. ( 27386757 )
2016
18
Conditional Alpl Ablation Phenocopies Dental Defects of Hypophosphatasia. ( 27582029 )
2016
19
Recognizing the clinical triad and dural calcification in adult hypophosphatasia. ( 27994097 )
2016
20
Pyridoxine Responsive Seizures in Infantile Hypophosphatasia and a Novel Homozygous Mutation in ALPL gene. ( 27086862 )
2016
21
Asfotase Alfa in Perinatal/Infantile-Onset and Juvenile-Onset Hypophosphatasia: A Guide to Its Use in the USA. ( 26832358 )
2016
22
Current concepts in odontohypophosphatasia form of hypophosphatasia and report of two cases. ( 27531358 )
2016
23
Pathophysiology of hypophosphatasia and the potential role of asfotase alfa. ( 27274262 )
2016
24
Hypophosphatasia: diagnosis and clinical signs - a dental surgeon perspective. ( 27030892 )
2016
25
Asfotase alfa (Strensiq) for hypophosphatasia. ( 27403786 )
2016
26
Treatment of hypophosphatasia by muscle-directed expression of bone-targeted alkaline phosphatase via self-complementary AAV8 vector. ( 26904710 )
2016
27
HYPOPHOSPHATASIA WITH THE ASSOCIATION OF INV(1)(q11,q21.3) AND CLEFT PALATE. ( 27192895 )
2016
28
ADULT HYPOPHOSPHATASIA TREATED WITH TERIPARATIDE: REPORT OF TWO PATIENTS AND REVIEW OF THE LITERATURE. ( 27042741 )
2016
29
Adult hypophosphatasia. ( 26962706 )
2016
30
Burden of disease in adult patients with hypophosphatasia: Results from two patient-reported surveys. ( 27621187 )
2016
31
Molecular defect of tissue-nonspecific alkaline phosphatase bearing a substitution at position 426 associated with hypophosphatasia. ( 28000043 )
2016
32
Gene therapy improves dental manifestations in hypophosphatasia model mice. ( 27561677 )
2016
33
Bone mineralization-dependent craniosynostosis and craniofacial shape abnormalities in the mouse model of infantile hypophosphatasia. ( 26605996 )
2016
34
Neurodevelopmental alterations and seizures developed by mouse model of infantile hypophosphatasia are associated with purinergic signalling deregulation. ( 27466191 )
2016
35
Alkaline Phosphatase and Hypophosphatasia. ( 26590809 )
2016
36
Asfotase alfa: enzyme replacement for the treatment of bone disease in hypophosphatasia. ( 27376160 )
2016
37
First Korean Case of Infantile Hypophosphatasia with Novel Mutation in ALPL and Literature Review. ( 27312557 )
2016
38
The Editor recommends this issue's article to the reader: Hypophosphatasia: diagnosis and clinical signs - a dental surgeon perspective. ( 27704676 )
2016
39
Hypophosphatasia: Evaluation of Size and Mineral Density of Exfoliated Teeth. ( 27805893 )
2016
40
Neurological Symptoms of Hypophosphatasia. ( 26219717 )
2015
41
Prenatal diagnosis of hypophosphatasia congenita using ultrasonography. ( 25971898 )
2015
42
Postnatal Pancraniosynostosis in a Patient With Infantile Hypophosphatasia. ( 26171568 )
2015
43
Hypophosphatasia: Validation and expansion of the clinical nosology for children from 25years experience with 173 pediatric patients. ( 25731960 )
2015
44
How Do we Estimate Quality Adjusted Life Years (Qalys) in Rare Diseases? A Case Study in Hypophosphatasia. ( 26533650 )
2015
45
Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. ( 26529632 )
2015
46
Expensive New Biologic Helps Children Fight Hypophosphatasia. ( 26803886 )
2015
47
Enzyme replacement for craniofacial skeletal defects and craniosynostosis in murine hypophosphatasia. ( 25959417 )
2015
48
Molecular diagnosis of hypophosphatasia and differential diagnosis by targeted Next Generation Sequencing. ( 26432670 )
2015
49
Hypophosphatasia: an overview of the disease and its treatment. ( 26245849 )
2015
50
Molecular Genetics of Hypophosphatasia and Phenotype-Genotype Correlations. ( 26219705 )
2015

Variations for Hypophosphatasia

ClinVar genetic disease variations for Hypophosphatasia:

6 (show all 12)
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.485G> T (p.Gly162Val) single nucleotide variant Pathogenic rs121918012 GRCh37 Chromosome 1, 21890546: 21890546
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.746G> T (p.Gly249Val) single nucleotide variant Pathogenic rs121918018 GRCh37 Chromosome 1, 21894694: 21894694
11 ALPL NM_000478.5(ALPL): c.526G> A (p.Ala176Thr) single nucleotide variant Pathogenic rs121918019 GRCh37 Chromosome 1, 21890587: 21890587
12 ALPL NM_000478.5(ALPL): c.814C> T (p.Arg272Cys) single nucleotide variant Pathogenic rs121918020 GRCh37 Chromosome 1, 21896819: 21896819

Expression for Hypophosphatasia

Search GEO for disease gene expression data for Hypophosphatasia.

Pathways for Hypophosphatasia

GO Terms for Hypophosphatasia

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

id Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 9.46 ALPL ANKH DSPP PTH
2 regulation of bone mineralization GO:0030500 9.32 ANKH ENPP1
3 inorganic diphosphate transport GO:0030505 9.26 ANKH ENPP1
4 response to vitamin D GO:0033280 9.13 ALPL PTH SPP1
5 biomineral tissue development GO:0031214 8.92 ALPL DSPP ENPP1 SPP1

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

id Name GO ID Score Top Affiliating Genes
1 catalytic activity GO:0003824 9.13 ALPL ALPP ENPP1
2 alkaline phosphatase activity GO:0004035 8.62 ALPL ALPP

Sources for Hypophosphatasia

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 Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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