MCID: HYP035
MIFTS: 50

Hypophosphatasia malady

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

Aliases & Classifications for Hypophosphatasia

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Sources:
10Disease Ontology, 21GeneReviews, 45NIH Rare Diseases, 22GeneTests, 23Genetics Home Reference, 47Novoseek, 12DISEASES, 51Orphanet, 36MeSH, 24GTR, 65UMLS, 27ICD10, 42NCIt, 59SNOMED-CT, 28ICD10 via Orphanet, 37MESH via Orphanet, 66UMLS via Orphanet
See all MalaCards sources

Aliases & Descriptions for Hypophosphatasia:

Name: Hypophosphatasia 10 21 45 22 23 47 12 51 36 24 65
Childhood Hypophosphatasia 10 45 65
Phosphoethanolaminuria 45 23 51
Childhood-Onset Phosphoethanolaminuria 45 51
Deficiency of Alkaline Phosphatase 10 23
Childhood-Onset Hypophosphatasia 45 51
Childhood-Onset Rathburn Disease 45 51
Rathburn Disease 45 51
 
Hypophosphatasia Childhood Type 24
Hereditary Pyropoikilocytosis 65
Hypophospatasia, Childhood 10
Infantile Hypophosphatasia 65
Phosphoethanol-Aminuria 45
Hypophosphatasia, Mild 47
Hypophosphatasia Mild 45
Hpp 51

Characteristics:

Orphanet epidemiological data:

51
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
childhood-onset phosphoethanolaminuria:
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Childhood,Infancy

Classifications:



External Ids:

Disease Ontology10 DOID:14213
ICD1027 E83.39
NCIt42 C26798
Orphanet51 436, 247667
ICD10 via Orphanet28 E83.3
MESH via Orphanet37 D007014
UMLS via Orphanet66 C0020630, C0220743
UMLS65 C0020630, C0220743, C0268412 C0520739, more

Summaries for Hypophosphatasia

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NIH Rare Diseases:45 Childhood hypophosphatasia is a form of hypophosphatasia, a rare condition that affects the bones. childhood hypophosphatasia, specifically, is generally diagnosed when the condition develops after six months of age but before adulthood. signs and symptoms vary but may include delayed motor milestones; low bone mineral density for age; early loss of baby teeth (before age 5); bone and joint pain; short stature; a waddling gait; skeletal malformations; and/or unexplained broken bones. the forms of hypophosphatasia that develop during childhood are generally more mild than those that appear in infancy. childhood hypophosphatasia is caused by changes (mutations) in the alpl gene and can be inherited in an autosomal dominant or autosomal recessive manner. treatment is supportive and based on the signs and symptoms present in each person. recently an enzyme replacement therapy (ert) called asfotase alfa has been show to improve bone symptoms in people with childhood hypophosphatasia and has been approved by the fda. last updated: 3/22/2016

MalaCards based summary: Hypophosphatasia, also known as childhood hypophosphatasia, is related to hypophosphatasia, infantile and hypophosphatasia, adult, and has symptoms including abnormality of the teeth, abnormality of the ribs and narrow chest. An important gene associated with Hypophosphatasia is ALPL (Alkaline Phosphatase, Liver/Bone/Kidney), and among its related pathways are Folate biosynthesis and Endochondral Ossification. Affiliated tissues include bone, lung and endothelial, and related mouse phenotype skeleton.

Genetics Home Reference:23 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.

Wikipedia:68 Hypophosphatasia is a rare, and sometimes fatal, metabolic bone disease. Clinical symptoms are... more...

GeneReviews summary for NBK1150

Related Diseases for Hypophosphatasia

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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 143)
idRelated DiseaseScoreTop Affiliating Genes
1hypophosphatasia, infantile34.2ALPL, ALPP
2hypophosphatasia, adult12.3
3hypophosphatasia, childhood12.1
4perinatal lethal hypophosphatasia12.1
5prenatal benign hypophosphatasia11.9
6pyropoikilocytosis11.5
7anaerobic meningitis10.6ALPL, ALPP
8breast adenocarcinoma10.6ALPL, ALPP
9cervical adenitis10.6ALPL, ALPP
10internal auditory canal meningioma10.6ALPL, ALPP
11malignant histiocytosis10.6ALPL, ALPP
12angiostrongyliasis10.6ALPL, ALPP
13achondrogenesis10.6ALPL, ALPP
14postgastrectomy syndrome10.6ALPL, ALPP
15arteritic anterior ischemic optic neuropathy10.6ALPL, ALPP
16fibrogenesis imperfecta ossium10.6ALPL, ALPP
17mixed cell type adenoma of parathyroid10.6ALPL, ALPP
18xanthogranulomatous cholecystitis10.6ALPL, ALPP
19axial osteomalacia10.6ALPL, ALPP
20brawny scleritis10.6ALPL, ALPP
21ovary rhabdomyosarcoma10.6ALPL, ALPP
22pancreatic ductal carcinoma10.6ALPL, ALPP
23larynx carcinoma in situ10.6ALPL, ALPP
24swine influenza10.6ALPL, ALPP
25pericholangitis10.6ALPL, ALPP
26gingival disease10.6ALPL, ALPP
27macrocytic anemia10.6ALPL, ALPP
28pseudomyxoma peritonei10.6ALPL, ALPP
29skeletal muscle cancer10.6ALPL, ALPP
30testicular germ cell cancer10.6ALPL, ALPP
31bartholin's gland adenocarcinoma10.6ALPL, ALPP
32geotrichosis10.6ALPL, ALPP
33dendritic cell thymoma10.6ALPL, ALPP
34central nervous system germ cell tumor10.6ALPL, ALPP
35venezuelan hemorrhagic fever10.6ALPL, ALPP
36hemometra10.6ALPL, ALPP
37diamond-blackfan anemia 410.6ALPL, ALPP
38alzheimer disease-210.6ALPL, ALPP
39paracoccidioidomycosis10.6ALPL, ALPP
40central nervous system sarcoma10.6ALPL, ALPP
41bile duct disease10.6ALPL, ALPP
42seminoma10.6ALPL, ALPP
43biliary tract disease10.6ALPL, ALPP
44leber congenital amaurosis 310.6ALPL, ALPP
45uremia10.6ALPL, ALPP
46splenic flexure cancer10.6ALPL, ALPP
47amebiasis10.6ALPL, ALPP
48duodenogastric reflux10.6ALPL, ALPP
49diabetic angiopathy10.6ALPL, ALPP
50inflammatory leiomyosarcoma10.6ALPL, ALPP

Graphical network of the top 20 diseases related to Hypophosphatasia:



Diseases related to hypophosphatasia

Symptoms for Hypophosphatasia

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Symptoms:

 51 (show all 20)
  • craniostenosis/craniosynostosis/sutural synostosis
  • large fontanelle/delayed fontanelle closure
  • anomalies of teeth and dentition
  • narrow rib cage/thorax
  • anomalies of the ribs
  • dermoid sinus/dimple/pit (excluding sacral)
  • emphysema
  • metaphyseal anomaly
  • bowed diaphysis/diaphyses/long bones
  • autosomal recessive inheritance
  • short stature/dwarfism/nanism
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • respiratory distress/dyspnea/respiratory failure/lung volume reduction
  • hypotonia
  • seizures/epilepsy/absences/spasms/status epilepticus
  • psychic/behavioural troubles
  • mutiple fractures/bone fragility
  • anaemia
  • hypercalcemia
  • stillbirth/neonatal death

HPO human phenotypes related to Hypophosphatasia:

(show all 16)
id Description Frequency HPO Source Accession
1 abnormality of the teeth hallmark (90%) HP:0000164
2 abnormality of the ribs hallmark (90%) HP:0000772
3 narrow chest hallmark (90%) HP:0000774
4 abnormality of the metaphyses hallmark (90%) HP:0000944
5 craniosynostosis hallmark (90%) HP:0001363
6 emphysema hallmark (90%) HP:0002097
7 short stature hallmark (90%) HP:0004322
8 bowing of the long bones hallmark (90%) HP:0006487
9 sacrococcygeal pilonidal abnormality hallmark (90%) HP:0010767
10 behavioral abnormality typical (50%) HP:0000708
11 seizures typical (50%) HP:0001250
12 muscular hypotonia typical (50%) HP:0001252
13 anemia typical (50%) HP:0001903
14 respiratory insufficiency typical (50%) HP:0002093
15 recurrent fractures typical (50%) HP:0002757
16 hypercalcemia typical (50%) HP:0003072

UMLS symptoms related to Hypophosphatasia:


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

Drugs & Therapeutics for Hypophosphatasia

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Interventional clinical trials:

(show all 20)
idNameStatusNCT IDPhase
1Post-approval Clinical Study of Asfotase Alfa Treatment for Patients With Hypophosphatasia (HPP) in JapanActive, not recruitingNCT02531867Phase 4
2Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)Active, not recruitingNCT01176266Phase 2, Phase 3
3Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)CompletedNCT00744042Phase 1, Phase 2
4Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)CompletedNCT01406977Phase 2
5Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)CompletedNCT00952484Phase 2
6Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP)CompletedNCT02456038Phase 2
7Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)Active, not recruitingNCT01163149Phase 2
8Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)Active, not recruitingNCT01205152Phase 2
9Extension Study of Protocol ENB-006-09 - Study of Asfotase Alfa in Children With Hypophosphatasia (HPP)Active, not recruitingNCT01203826Phase 2
10Safety and Efficacy Study of ENB-0040 in Juvenile Patients With Hypophosphatasia (HPP)WithdrawnNCT00894075Phase 2
11Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)CompletedNCT00739505Phase 1
12Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP)Approved for marketingNCT02496689
13A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)CompletedNCT01419028
14Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP)CompletedNCT02104219
15Non-interventional Substudy of ALX-HPP-502 to Assess Natural History of Patients With Juvenile-onset HPP Who Served as Historical Controls in ENB-006-09CompletedNCT02235493
16Biomarker for Hypophosphatasia DiseaseRecruitingNCT02603042
17Natural History Study of Patients With Hypophosphatasia (HPP)RecruitingNCT02237625
18Burden of Disease in Hypophosphatasia (HPP)RecruitingNCT02291497
19An Observational, Longitudinal, Prospective, Long-Term Registry Of Patients With Hypophosphatasia (HPP)Enrolling by invitationNCT02306720
20Health Burden of HypophosphatasiaNot yet recruitingNCT02751801

Search NIH Clinical Center for Hypophosphatasia


Cochrane evidence based reviews: hypophosphatasia

Genetic Tests for Hypophosphatasia

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Genetic tests related to Hypophosphatasia:

id Genetic test Affiliating Genes
1 Hypophosphatasia22 ALPL

Anatomical Context for Hypophosphatasia

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MalaCards organs/tissues related to Hypophosphatasia:

33
Bone, Lung, Endothelial, Thyroid, Ovary, T cells, Breast

Animal Models for Hypophosphatasia or affiliated genes

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MGI Mouse Phenotypes related to Hypophosphatasia:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053907.8ALPL, ANKH, ENPP1, PHEX, SPTA1

Publications for Hypophosphatasia

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Articles related to Hypophosphatasia:

(show top 50)    (show all 496)
idTitleAuthorsYear
1
Hypophosphatasia: diagnosis and clinical signs - a dental surgeon perspective. (27030892)
2016
2
Hypophosphatasia. (27084188)
2016
3
Molecular diagnosis of hypophosphatasia and differential diagnosis by targeted Next Generation Sequencing. (26432670)
2015
4
Enzyme replacement for craniofacial skeletal defects and craniosynostosis in murine hypophosphatasia. (25959417)
2015
5
Enzyme replacement therapy for congenital hypophosphatasia allows for surgical treatment of related complex craniosynostosis: a case series. (25929963)
2015
6
Hypophosphatasia: an overview of the disease and its treatment. (26245849)
2015
7
Prenatal diagnosis of hypophosphatasia congenita using ultrasonography. (25971898)
2015
8
Infantile hypophosphatasia without bone deformities presenting with severe pyridoxine-resistant seizures. (24100244)
2013
9
Infantile hypophosphatasia secondary to a novel compound heterozygous mutation presenting with pyridoxine-responsive seizures. (23479201)
2013
10
Did Tutankhamun suffer from hypophosphatasia?--A hypothetical approach. (24466636)
2013
11
Hypophosphatasia-associated deficiencies in mineralization and gene expression in cultured dental pulp cells obtained from human teeth. (22703652)
2012
12
Bone quality changes in 3 cases of hypophosphatasia: a FTIRI study. (24134971)
2012
13
In silico scoring of ALPL gene mutations help to distinguish severe and moderate phenotypes in hypophosphatasia. (24134979)
2012
14
Lack of sustained response to teriparatide in a patient with adult hypophosphatasia. (20089612)
2010
15
Orodental phenotype and genotype findings in all subtypes of hypophosphatasia. (19232125)
2009
16
Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. (19113923)
2009
17
Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles. (19500388)
2009
18
Molecular basis of perinatal hypophosphatasia with tissue-nonspecific alkaline phosphatase bearing a conservative replacement of valine by alanine at position 406. Structural importance of the crown domain. (18422967)
2008
19
Specific ultrasonographic features of perinatal lethal hypophosphatasia. (18386808)
2008
20
A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb the cell localization of the wild-type protein. (18340466)
2008
21
Therapy for hypophosphatasia]. (17906415)
2007
22
Neonatal hypophosphatasia and seizures. A case report. (16205618)
2005
23
Characterization of 11 novel mutations in the tissue non-specific alkaline phosphatase gene responsible for hypophosphatasia and genotype-phenotype correlations. (15694177)
2005
24
Sustained osteomalacia of long bones despite major improvement in other hypophosphatasia-related mineral deficits in tissue nonspecific alkaline phosphatase/nucleotide pyrophosphatase phosphodiesterase 1 double-deficient mice. (15920156)
2005
25
Mutational analysis and functional correlation with phenotype in German patients with childhood-type hypophosphatasia. (11760847)
2001
26
A molecular approach to dominance in hypophosphatasia. (11479741)
2001
27
Comparison of serum catalytic activity and immunoreactivity of bone alkaline phosphatase in hypophosphatasia. (10727673)
2000
28
Hypophosphatasia: diagnostic application of linked DNA markers in the dominantly inherited adult form. (10369796)
1999
29
Expression of the mutant (1735T-DEL) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia patients. (9844100)
1998
30
Adult hypophosphatasia in an aged patient. (9272313)
1997
31
Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy. (7706447)
1995
32
Recurrent calcific periarthritis, erosive osteoarthritis and hypophosphatasia: a family study. (2290172)
1990
33
Increased plasma pyridoxal-5'-phosphate levels before and after pyridoxine loading in carriers of perinatal/infantile hypophosphatasia. (2079838)
1990
34
Hyperphosphatemia in infantile hypophosphatasia: implications for carrier diagnosis and screening. (2301398)
1990
35
Ectopic calcification in hypophosphatasia. (3769946)
1986
36
Inheritance of hypophosphatasia. (4069031)
1985
37
Histologic and ultrastructural studies on the mineralization process in hypophosphatasia. (4073124)
1985
38
Hypophosphatasia (adult form): quantitation of serum alkaline phosphatase isoenzyme activity in a large kindred. (7379306)
1980
39
Hypophosphatasia: biochemical diagnosis in post-mortem organs, plasma and diploid skin fibroblasts [proceedings]. (93946)
1979
40
Hypophosphatasia. Review of 24 cases. (1012798)
1976
41
The diagnosis of the early infantile form of hypophosphatasia tarda. (1150259)
1975
42
Fatal neonatal dwarfism: examples of thanatophoric dwarfism and of hypophosphatasia. (4618133)
1974
43
Hyperparathyroidism in an elderly adult with hypophosphatasia. (4837933)
1974
44
Hypophosphatasia. (5020955)
1972
45
Radiological case of the month. Hypophosphatasia in the newborn. (4327541)
1971
46
Phosphorylethanolamine and hypophosphatasia. (4306219)
1968
47
HYPOPHOSPHATASIA. A METABOLIC DISEASE WITH IMPORTANT DENTAL MANIFESTATIONS. (14230754)
1964
48
Hypophosphatasia: a genetic study. (14490519)
1961
49
HYPOPHOSPHATASIA. (13575173)
1958
50

Variations for Hypophosphatasia

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Clinvar genetic disease variations for Hypophosphatasia:

5
id Gene Variation Type Significance SNP ID Assembly Location
1ALPLNM_000478.5(ALPL): c.571G> A (p.Glu191Lys)single nucleotide variantPathogenicrs121918007GRCh37Chr 1, 21890632: 21890632
2ALPLNM_000478.5(ALPL): c.1133A> T (p.Asp378Val)single nucleotide variantPathogenicrs121918008GRCh37Chr 1, 21902361: 21902361
3ALPLNM_000478.5(ALPL): c.1001G> A (p.Gly334Asp)single nucleotide variantPathogenicrs121918009GRCh37Chr 1, 21902229: 21902229
4ALPLNM_000478.5(ALPL): c.979T> C (p.Phe327Leu)single nucleotide variantPathogenicrs121918010GRCh37Chr 1, 21900274: 21900274
5ALPLNM_000478.5(ALPL): c.1559delT (p.Leu520Argfs)deletionPathogenicrs387906525GRCh37Chr 1, 21904125: 21904125

Expression for genes affiliated with Hypophosphatasia

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Search GEO for disease gene expression data for Hypophosphatasia.

Pathways for genes affiliated with Hypophosphatasia

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Pathways related to Hypophosphatasia according to GeneCards Suite gene sharing:

idSuper pathwaysScoreTop Affiliating Genes
19.8ALPL, ALPP
29.7ALPL, ENPP1
3
Show member pathways
9.3ALPL, ALPP, ENPP1

GO Terms for genes affiliated with Hypophosphatasia

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

idNameGO IDScoreTop Affiliating Genes
1inorganic diphosphate transportGO:00305059.2ANKH, ENPP1

Sources for Hypophosphatasia

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet