MCID: HYP035
MIFTS: 56

Hypophosphatasia malady

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

Aliases & Classifications for Hypophosphatasia

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Sources:
11Disease Ontology, 22GeneReviews, 46NIH Rare Diseases, 23GeneTests, 24Genetics Home Reference, 13DISEASES, 52Orphanet, 25GTR, 48Novoseek, 37MeSH, 66UMLS, 28ICD10, 43NCIt, 29ICD10 via Orphanet, 38MESH via Orphanet, 67UMLS via Orphanet, 60SNOMED-CT
See all MalaCards sources

Aliases & Descriptions for Hypophosphatasia:

Name: Hypophosphatasia 11 22 46 23 24 13 52 25 48 37 66
Childhood Hypophosphatasia 11 46 66
Phosphoethanolaminuria 46 24 52
Deficiency of Alkaline Phosphatase 11 24
Rathburn Disease 46 52
Childhood-Onset Phosphoethanolaminuria 46
Childhood-Onset Hypophosphatasia 46
Childhood-Onset Rathburn Disease 46
Hypophosphatasia Childhood Type 25
 
Hereditary Pyropoikilocytosis 66
Hypophosphatasia, Childhood 37
Infantile Hypophosphatasia 66
Hypophospatasia, Childhood 11
Phosphoethanol-Aminuria 46
Hypophosphatasia, Mild 48
Hypophosphatasia Mild 46
Hpp 52

Characteristics:

Orphanet epidemiological data:

52
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 Ontology11 DOID:14213
ICD1028 E83.39
NCIt43 C26798
Orphanet52 ORPHA436
ICD10 via Orphanet29 E83.3
MESH via Orphanet38 D007014
UMLS via Orphanet67 C0020630

Summaries for Hypophosphatasia

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NIH Rare Diseases:46 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 Development_Hedgehog and PTH signaling pathways in bone and cartilage development. Affiliated tissues include bone, skin and bone marrow, and related mouse phenotypes are obsolete other and craniofacial.

Genetics Home Reference:24 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:69 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 60)
idRelated DiseaseScoreTop Affiliating Genes
1hypophosphatasia, infantile34.1ALPL, ALPP
2hypophosphatasia, adult12.3
3hypophosphatasia, childhood12.2
4prenatal benign hypophosphatasia11.9
5pyropoikilocytosis11.5
6anterolateral myocardial infarction10.4ALPL, ALPP
7spastic ataxia10.3ENPP1, PHEX
8atelosteogenesis10.3ENPP1, PHEX
9prostate cancer, hereditary, x-linked 210.3ENPP1, PHEX
10commensal bacterial infectious disease10.2ENPP1, PHEX
11loeys-dietz syndrome10.2PHEX, RUNX2
12tuberous sclerosis-110.2ENPP1, PHEX
13leukodystrophy10.2ALPL, PHEX
14periodontitis10.2
15bone deterioration disease10.2PHEX, RUNX2
16status epilepticus10.1ENPP1, PHEX
17jackson-weiss syndrome10.1ALPL, RUNX2
18hypercalcemia10.0
19protein-losing enteropathy10.0ALPL, ENPP1, PHEX
20pleomorphic adenoma carcinoma10.0ALPL, ANKH
21y-linked disease10.0ALPL, DLX3
22cleidocranial dysplasia10.0
23craniosynostosis10.0
24osteogenesis imperfecta10.0
25pancreatitis10.0
26psoriasis10.0
27osteomyelitis9.9
28renal osteodystrophy9.9
29hyperparathyroidism9.9
30periarthritis9.9
31periodontal disease9.9
32arthropathy9.9
33myopathy9.9
34vulvovaginal candidiasis9.8ALPL, ANKH
35phenylketonuria9.7
36chronic recurrent multifocal osteomyelitis9.7
37west syndrome9.7
38hepatitis9.7
39keratopathy9.7
40leukemia9.7
41osteoarthritis9.7
42retinitis pigmentosa9.7
43hypophosphatemia9.7
44hyperphosphatemia9.7
45osteomalacia9.7
46band keratopathy9.7
47chondrocalcinosis9.7
48nephrotic syndrome9.7
49nephrocalcinosis9.7
50gingivitis9.7

Graphical network of the top 20 diseases related to Hypophosphatasia:



Diseases related to hypophosphatasia

Symptoms for Hypophosphatasia

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Symptoms:

 52 (show all 20)
  • abnormality of the teeth
  • large fontanelles
  • irritability
  • abnormality of the ribs
  • narrow chest
  • abnormality of the metaphyses
  • skin dimple over apex of long bone angulation
  • seizures
  • muscular hypotonia
  • craniosynostosis
  • failure to thrive in infancy
  • anemia
  • respiratory insufficiency
  • emphysema
  • recurrent fractures
  • hypercalcemia
  • short stature
  • bowing of the long bones
  • feeding difficulties in infancy
  • skin dimples

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:


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

Drugs & Therapeutics for Hypophosphatasia

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Interventional clinical trials:

(show all 23)
idNameStatusNCT IDPhase
1Post-approval Clinical Study of Asfotase Alfa Treatment for Patients With Hypophosphatasia (HPP) in JapanCompletedNCT02531867Phase 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 Adolescents and Adults With Hypophosphatasia (HPP)CompletedNCT01163149Phase 2
4Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)CompletedNCT01205152Phase 2
5Extension Study of Protocol ENB-006-09 - Study of Asfotase Alfa in Children With Hypophosphatasia (HPP)CompletedNCT01203826Phase 2
6Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)CompletedNCT00744042Phase 1, Phase 2
7Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)CompletedNCT01406977Phase 2
8Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)CompletedNCT00952484Phase 2
9Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP)CompletedNCT02456038Phase 2
10Pharmacokinetic, and Dose Response Study of Asfotase Alfa in Adult Patients With Pediatric-Onset Hypophosphatasia (HPP)RecruitingNCT02797821Phase 2
11Safety and Efficacy Study of ENB-0040 in Juvenile Patients With Hypophosphatasia (HPP)WithdrawnNCT00894075Phase 2
12Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein Asfotase Alfa in Adults With Hypophosphatasia (HPP)CompletedNCT00739505Phase 1
13Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP)Approved for marketingNCT02496689
14A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)CompletedNCT01419028
15Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP)CompletedNCT02104219
16Non-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
17Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at SanfordRecruitingNCT01793168
18Biomarker for Hypophosphatasia DiseaseRecruitingNCT02603042
19Natural History Study of Patients With Hypophosphatasia (HPP)RecruitingNCT02237625
20Burden of Disease in Hypophosphatasia (HPP)RecruitingNCT02291497
21An Observational, Longitudinal, Prospective, Long-Term Registry Of Patients With Hypophosphatasia (HPP)Enrolling by invitationNCT02306720
22Characterisation of Adult-Onset HypophosphatasiaNot yet recruitingNCT02796885
23Health 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 Hypophosphatasia25 23 ALPL
2 Childhood Hypophosphatasia25

Anatomical Context for Hypophosphatasia

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MalaCards organs/tissues related to Hypophosphatasia:

34
Bone, Skin, Bone marrow, Liver, Kidney, Testes, Neutrophil

Animal Models for Hypophosphatasia or affiliated genes

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MGI Mouse Phenotypes related to Hypophosphatasia:

39 (show all 11)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:000539510.3ALPL, PHEX
2MP:00053828.9ALPL, ANKH, PHEX, RUNX2
3MP:00053698.2ALPL, ANKH, ENPP1, PLCB4, RUNX2
4MP:00053718.2ALPL, ANKH, PHEX, RUNX2
5MP:00053878.0ALPL, ANKH, ENPP1, PHEX, RUNX2, SPTA1
6MP:00036317.9ALPL, ENPP1, PHEX, PLCB4, RUNX2, SPTA1
7MP:00053857.6ALPL, ANKH, DLX3, ENPP1, RUNX2, SPTA1
8MP:00053867.3ALPL, ANKH, ENPP1, PHEX, PLCB4, SPTA1
9MP:00053906.9ALPL, ANKH, ENPP1, PHEX, PLCB4, RUNX2
10MP:00107686.6ALPL, ANKH, DLX3, ENPP1, PHEX, PLCB4
11MP:00053786.4ALPL, ANKH, DLX3, ENPP1, PHEX, PLCB4

Publications for Hypophosphatasia

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Articles related to Hypophosphatasia:

(show top 50)    (show all 508)
idTitleAuthorsYear
1
Hypophosphatasia: diagnosis and clinical signs - a dental surgeon perspective. (27030892)
2016
2
Hypophosphatasia. (27084188)
2016
3
Hypophosphatasia: an overview of the disease and its treatment. (26245849)
2015
4
Neurological Symptoms of Hypophosphatasia. (26219717)
2015
5
Infantile hypophosphatasia without bone deformities presenting with severe pyridoxine-resistant seizures. (24100244)
2013
6
Hypophosphatasia-associated deficiencies in mineralization and gene expression in cultured dental pulp cells obtained from human teeth. (22703652)
2012
7
In silico scoring of ALPL gene mutations help to distinguish severe and moderate phenotypes in hypophosphatasia. (24134979)
2012
8
Evolutionary analysis of ALPL validates and predicts human mutations leading to hypophosphatasia. (24134978)
2012
9
Perinatal (lethal) type of hypophosphatasia resulting from paternal isodisomy of chromosome 1. (24134977)
2012
10
Identification of the mutations in the tissue-nonspecific alkaline phosphatase gene in two Chinese families with hypophosphatasia. (22300680)
2012
11
Orodental phenotype and genotype findings in all subtypes of hypophosphatasia. (19232125)
2009
12
Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles. (19500388)
2009
13
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. (19335222)
2009
14
A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb the cell localization of the wild-type protein. (18340466)
2008
15
Hyperechoic metaphyses in hypophosphatasia: what does it mean? (18084754)
2008
16
Bone-targeted replacement therapy for hypophosphatasia. (18318644)
2008
17
Long-term follow-up of bone mineral density in childhood hypophosphatasia. (17420150)
2007
18
Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene. (17395561)
2007
19
Aberrant interchain disulfide bridge of tissue-nonspecific alkaline phosphatase with an Arg433-->Cys substitution associated with severe hypophosphatasia. (17212778)
2006
20
Neonatal hypophosphatasia and seizures. A case report. (16205618)
2005
21
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
22
Positive maternal serum triple test screening in severe early onset hypophosphatasia. (15300736)
2004
23
Comparison of serum catalytic activity and immunoreactivity of bone alkaline phosphatase in hypophosphatasia. (10727673)
2000
24
Expression of the mutant (1735T-DEL) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia patients. (9844100)
1998
25
Hypophosphatasia: identification of five novel missense mutations (G507A, G705A, A748G, T1155C, G1320A) in the tissue-nonspecific alkaline phosphatase gene among Japanese patients. (9452105)
1998
26
Adult hypophosphatasia in an aged patient. (9272313)
1997
27
Childhood hypophosphatasia. A case report. (9188264)
1997
28
Renal osteodystrophy, disorders of vitamin D metabolism, and hypophosphatasia. (1599820)
1992
29
Prenatal diagnosis of infantile hypophosphatasia. (1680232)
1991
30
Recurrent calcific periarthritis, erosive osteoarthritis and hypophosphatasia: a family study. (2290172)
1990
31
Hyperphosphatemia in infantile hypophosphatasia: implications for carrier diagnosis and screening. (2301398)
1990
32
Infantile hypophosphatasia: localization within chromosome region 1p36.1-34 and prenatal diagnosis using linked DNA markers. (1689104)
1990
33
Biochemical and morphological effects of human hepatic alkaline phosphatase in a neonate with hypophosphatasia. (2642253)
1989
34
First identification of a gene defect for hypophosphatasia: evidence that alkaline phosphatase acts in skeletal mineralization. (2605956)
1989
35
Infantile hypophosphatasia--linkage with the RH locus. (3128473)
1987
36
Normal activity of nucleoside triphosphate pyrophosphatase in alkaline phosphatase-deficient fibroblasts from patients with infantile hypophosphatasia. (3020080)
1986
37
Inheritance of hypophosphatasia. (4069031)
1985
38
Normal circulating acid phosphatase activity in hypophosphatasia. (3939595)
1985
39
Adult hypophosphatasia without apparent skeletal disease: "odontohypophosphatasia" in four heterozygote members of a family. (6727276)
1984
40
Isoenzymes of alkaline phosphatase in infantile hypophosphatasia. (6854132)
1983
41
Infantile hypophosphatasia diagnosed at 4 months and surviving at 2 years. (7085329)
1982
42
Alkaline phosphatase induction in fibroblast cultures: prenatal diagnosis and carrier detection in hypophosphatasia. (723908)
1978
43
Hypophosphatasia. Review of 24 cases. (1012798)
1976
44
The diagnosis of the early infantile form of hypophosphatasia tarda. (1150259)
1975
45
Fatal neonatal dwarfism: examples of thanatophoric dwarfism and of hypophosphatasia. (4618133)
1974
46
Childhood hypophosphatasia. Clinical and cytogenetic studies. (4506889)
1972
47
Radiological case of the month. Hypophosphatasia in the newborn. (4327541)
1971
48
Hypophosphatasia. (5236694)
1967
49
Hypophosphatasia with premature shedding of teeth and aplasia of cementum. (14016153)
1962
50
HYPOPHOSPHATASIA. (13575173)
1958

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
29.4PLCB4, RUNX2
3
Show member pathways
9.4ALPL, ALPP, ENPP1
49.4ALPL, ENPP1, RUNX2

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:00305059.8ANKH, ENPP1
2hemopoiesisGO:00300979.7RUNX2, SPTA1
3endochondral ossificationGO:00019589.6ALPL, RUNX2
4odontogenesis of dentin-containing toothGO:00424759.5DLX3, RUNX2
5regulation of bone mineralizationGO:00305009.4ANKH, ENPP1
6skeletal system developmentGO:00015018.5ALPL, ANKH, PHEX, RUNX2

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

idNameGO IDScoreTop Affiliating Genes
1alkaline phosphatase activityGO:00040359.8ALPL, ALPP

Sources for Hypophosphatasia

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet