HPP
MCID: HYP035
MIFTS: 73

Hypophosphatasia (HPP) malady

Bone diseases, Fetal diseases, Genetic diseases categories

Summaries for Hypophosphatasia

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42NIH Rare Diseases, 21Genetics Home Reference, 63Wikipedia, 46OMIM, 19GeneReviews, 32MalaCards
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NIH Rare Diseases:42 Hypophosphatasia is a genetic condition in which the activity of an enzyme called alkaline phosphatase is deficient.  this enzyme plays an essential role in mineralization - when minerals such as calcium and phosphorus are deposited in developing bones and teeth.  low activity of this enzyme which characterizes hypophosphatasia also leads to rickets, osteomalacia, or both.  the severity of the symptoms of hypophosphatasia varies widely, from fetal loss during pregnancy to cases in which pathologic fractures first present only in adulthood.  hypophosphatasia is caused by a mutation in a gene - called the alpl gene - that provides instructions for making the alkaline phosphatase enzyme. a cure or proven medical therapy for hypophosphatasia has not yet been found. treatment is generally directed towards preventing or correcting the symptoms or complications. last updated: 11/4/2009

MalaCards: Hypophosphatasia, also known as hypophosphatasia, childhood, is related to hyperthyroidism and thyroiditis, and has symptoms including dermoid sinus/dimple/pit (excluding sacral), hypercalcemia and craniostenosis/craniosynostosis/sutural synostosis. An important gene associated with Hypophosphatasia is ALPL (alkaline phosphatase, liver/bone/kidney), and among its related pathways are Endochondral Ossification and Folate biosynthesis. The compounds fluorides and strontium ranelate have been mentioned in the context of this disorder. Affiliated tissues include bone, skin and lung, and related mouse phenotypes are respiratory system and skeleton.

Genetics Home Reference:21 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:63 Hypophosphatasia is a rare, and sometimes fatal metabolic bone disease. Clinical symptoms are... more...

Description from OMIM:46 241500,241510,146300

GeneReviews summary for hops

Aliases & Classifications for Hypophosphatasia

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8Disease Ontology, 9diseasecard, 19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 60UMLS, 56SNOMED-CT, 34MeSH, 39NCIt, 35MESH via Orphanet, 26ICD10 via Orphanet, 57SNOMED-CT via Orphanet, 61UMLS via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Fetal diseases, Genetic diseases
Anatomical: Bone diseases


Characteristics (Orphanet epidemiological data):

48
hypophosphatasia:
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Variable; Age of death: Any age
childhood-onset phosphoethanolaminuria:
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Childhood


Aliases & Descriptions:

hypophosphatasia 8 19 42 20 22 21 10 44 48 60
hypophosphatasia, childhood 9 46 44
childhood hypophosphatasia 8 42 60
deficiency of alkaline phosphatase 8 21
hypophosphatasia childhood 42 22
phosphoethanolaminuria 21 48
autosomal recessive hypophosphatemic bone disease 60
hyperpigmentation, familial progressive 60
childhood-onset phosphoethanolaminuria 48
childhood-onset rathburn disease 48
childhood-onset hypophosphatasia 48
hypokalemic periodic paralysis 60
hypophospatasia, childhood 8
infantile hypophosphatasia 60
phosphoethanol-aminuria 42
hypophosphatasia, mild 44
hypophosphatasia mild 42
rathburn disease 48
hhrh 42
hpp 48


External Ids:

Disease Ontology8 DOID:14213
MeSH34 D007014
NCIt39 C26798
MESH via Orphanet35 D007014
ICD10 via Orphanet26 E83.3
SNOMED-CT via Orphanet57 190859005, 360792001, 30174008
UMLS via Orphanet61 C0020630, C0220743

Related Diseases for Hypophosphatasia

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17GeneCards, 18GeneDecks
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Diseases in the Hypophosphatasia family:

Hypophosphatasia, Adult

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

(show top 50)    (show all 142)
idRelated DiseaseScoreTop Affiliating Genes
1hyperthyroidism30.8ALPPL2, ALPP, ALPL, SLPI
2thyroiditis30.6CALCA
3hypophosphatasia, infantile30.5ALPL, ALPP
4hypercalcemia30.2ALPPL2, ALPP, ALPL, SLPI, CALCA
5osteogenesis imperfecta30.2ALPPL2, ALPP, ALPL, DSPP
6cleidocranial dysplasia30.2ALPL, RUNX2
7periodontal disease30.0DSPP, SLPI, ALPP
8arthropathy30.0ALPL, ANKH
9renal osteodystrophy30.0CALCA, SLPI, ALPL, ALPP, ALPPL2
10hyperparathyroidism30.0CALCA, SLPI, ALPL, ALPP, ALPPL2
11pancreatitis29.9ALPL, ALPP, ALPPL2
12gingivitis29.8ALPP, DSPP
13hepatitis29.8CCL27, ALPP
14x-linked hypophosphatemia29.8DSPP, ENPP1
15hyperphosphatemia29.8RUNX2, SLPI, ALPL, ALPP, ALPPL2
16hypophosphatemia29.8CALCA, ALPPL2, ALPP, ALPL, DSPP
17osteomalacia29.8CALCA, SLPI, ALPPL2, ALPP, ALPL
18osteoarthritis29.8RUNX2, CALCA, DSPP, ANKH, IL1R1, SLPI
19renal tubular acidosis10.7
20thyrotoxicosis10.6
21hypokalemic periodic paralysis type 110.6
22graves' disease10.5
23hypokalemic periodic paralysis type 210.5
24malignant hyperthermia10.5
25multiple sclerosis10.5
26sjogren's syndrome10.4
27hypokalemia10.4
28adenoma10.4
29myasthenia gravis10.4
30thyrotoxic periodic paralysis 110.4
31periodontitis10.3
32hereditary hypophosphatemic rickets with hypercalciuria10.3
33autosomal recessive congenital stationary night blindness10.3
34hyperpigmentation, familial progressive, 210.2
35hyperpigmentation, familial progressive, 110.2
36hypokalemic periodic paralysis10.2
37pyropoikilocytosis10.2
38membranoproliferative glomerulonephritis10.2
39wolff-parkinson-white syndrome10.2
40hyperuricemia10.2
41andersen-tawil syndrome10.2
42superior mesenteric artery syndrome10.2
43diabetes insipidus10.2
44amelogenesis imperfecta10.2
45tropical sprue10.2
46gynecomastia10.2
47hyperkalemic periodic paralysis10.2
48nephrogenic diabetes insipidus10.2
49facial paralysis10.2
50glomerulonephritis10.2

Graphical network of the top 20 diseases related to Hypophosphatasia:



Diseases related to hypophosphatasia

Clinical Features for Hypophosphatasia

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46OMIM, 48Orphanet
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Clinical features from OMIM:

241500,241510,146300

Clinical synopsis from OMIM:

241510

Symptoms:

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

Drugs & Therapeutics for Hypophosphatasia

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-RT
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Approved drugs:

Search CenterWatch for Hypophosphatasia

Drug clinical trials:

Search ClinicalTrials for Hypophosphatasia

Search NIH Clinical Center for Hypophosphatasia

Search CenterWatch for Hypophosphatasia

Genetic Tests for Hypophosphatasia

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20GeneTests, 22GTR
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Genetic tests related to Hypophosphatasia:

id Genetic test Affiliating Genes
1 Hypophosphatasia20 22 ALPL
2 Childhood Hypophosphatasia22

Anatomical Context for Hypophosphatasia

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32MalaCards
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MalaCards organs/tissues related to Hypophosphatasia:

32
Bone, Skin, Lung, Kidney, Liver, Testes, Bone marrow, Endothelial, Eye

Animal Models for Hypophosphatasia or affiliated genes

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36MGI
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MGI Mouse Phenotypes related to Hypophosphatasia:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053889.1RUNX2, ANKH, IL1R1, SPTA1, ALPL
2MP:00053909.0PHOSPHO1, ANKH, ENPP1, SPTA1, ALPL
3MP:00053767.8CALCA, PHOSPHO1, ANKH, IL1R1, SLPI, ENPP1
4MP:00053867.6CALCA, PHOSPHO1, ANKH, IL1R1, KHDRBS3, ENPP1
5MP:00107686.8ALPP, RUNX2, CALCA, PHOSPHO1, ANKH, IL1R1

Publications for Hypophosphatasia

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50PubMed
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Articles related to Hypophosphatasia:

(show top 50)    (show all 450)
idTitleAuthorsYear
1
Identification of the mutations in the tissue-nonspecific alkaline phosphatase gene in two Chinese families with hypophosphatasia. (22300680)
2012
2
Enzyme replacement prevents enamel defects in hypophosphatasia mice. (22461224)
2012
3
A dimerization defect caused by a glycine substitution at position 420 by serine in tissue-nonspecific alkaline phosphatase associated with perinatal hypophosphatasia. (23039266)
2012
4
Hypophosphatasia: a series of diagnosis missteps. (24134970)
2012
5
Acute severe hypercalcemia after traumatic fracture and immobilization in an adult with hypophosphatasia complicated by renal failure. (24134972)
2012
6
Novel heterozygous tissue-nonspecific alkaline phosphatase (TNAP) gene mutations causing lethal perinatal hypophosphatasia. (21638016)
2012
7
Hypophosphatasia in a child with widened anterior fontanelle: lessons learned from late diagnosis and incorrect treatment. (21342251)
2011
8
Clinical, pathological and genetic evaluations of Chinese patients with autosomal-dominant hypophosphatasia. (20828673)
2010
9
Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles. (19500388)
2009
10
How can calcium pyrophosphate crystals induce inflammation in hypophosphatasia or chronic inflammatory joint diseases? (18821074)
2009
11
Delayed transport of tissue-nonspecific alkaline phosphatase with missense mutations causing hypophosphatasia. (17719863)
2007
12
Specific osseous spurs in a lethal form of hypophosphatasia correlated with 3D prenatal ultrasonographic images. (17238218)
2007
13
Hypophosphatasia. (17916236)
2007
14
Analysis of the periodontal microbiota in childhood-type hypophosphatasia. (16875876)
2006
15
Neonatal hypophosphatasia and seizures. A case report. (16205618)
2005
16
Characterization of the mutant (A115V) tissue-nonspecific alkaline phosphatase gene from adult-type hypophosphatasia. (15629439)
2005
17
Bilateral transverse (Bowdler) fibular spurs with hypophosphatasia in an adolescent girl. (15782022)
2005
18
Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene. (15671102)
2005
19
Positive maternal serum triple test screening in severe early onset hypophosphatasia. (15300736)
2004
20
Pyridoxine-dependent seizures associated with hypophosphatasia in a newborn. (12026240)
2002
21
Retention at the cis-Golgi and delayed degradation of tissue-non-specific alkaline phosphatase with an Asn153-->Asp substitution, a cause of perinatal hypophosphatasia. (11802776)
2002
22
Characterization of a family with dominant hypophosphatasia. (10872988)
2000
23
Possible interference between tissue-non-specific alkaline phosphatase with an Arg54-->Cys substitution and acounterpart with an Asp277-->Ala substitution found in a compound heterozygote associated with severe hypophosphatasia. (10839996)
2000
24
Neutrophil alkaline phosphatase (NAP) score in the diagnosis of hypophosphatasia. (11074063)
2000
25
Hypophosphatasia: diagnostic application of linked DNA markers in the dominantly inherited adult form. (10369796)
1999
26
Expression of the mutant (1735T-DEL) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia patients. (9844100)
1998
27
Relationship between serum alkaline phosphatase and pyridoxal-5'-phosphate levels in hypophosphatasia. (9536930)
1998
28
Infantile hypophosphatasia: treatment options to control hypercalcemia, hypercalciuria, and chronic bone demineralization. (9152296)
1997
29
Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. (1409720)
1992
30
Hypophosphatasia and the extracellular metabolism of inorganic pyrophosphate: clinical and laboratory aspects. (1647780)
1991
31
Analysis of liver/bone/kidney alkaline phosphatase mRNA, DNA, and enzymatic activity in cultured skin fibroblasts from 14 unrelated patients with severe hypophosphatasia. (2705456)
1989
32
Hypophosphatasia: biochemical screening of a Dutch kindred and evidence that urinary excretion of inorganic pyrophosphate is a marker for the disease. (2843309)
1988
33
A mild form of hypophosphatasia as a cause of premature exfoliation of primary teeth: report of two cases. (3472186)
1987
34
Hypophosphatasia and nephrocalcinosis demonstrated by ultrasound and CT. (6396009)
1984
35
Hypophosphatasia. (6572063)
1983
36
Fetal congenital lethal hypophosphatasia: histochemical absence of alkaline phosphatase activity in endothelial cells of intramuscular capillaries. (6214919)
1982
37
Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred. (7072744)
1982
38
Hypophosphatasia (adult form): quantitation of serum alkaline phosphatase isoenzyme activity in a large kindred. (7379306)
1980
39
Hypophosphatasia: screening and family investigation. (4426133)
1974
40
Childhood hypophosphatasia and the premature loss of teeth. A clinical and laboratory study of seven cases. (4512507)
1973
41
Hypophosphatasia: a case report. (4310771)
1969
42
Hypophosphatasia. Histopathology of human temporal bones. (4312121)
1968
43
Studies in hypophosphatasia and response to high phosphate intake. (4296178)
1968
44
Hypophosphatasia. (5236694)
1967
45
Hypophosphatasia. (4288607)
1966
46
Hypophosphatasia. (5825726)
1965
47
HYPOPHOSPHATASIA. (13575173)
1958
48
The isolation and identification of phosphoethanolamine from the urine of a case of hypophosphatasia. (13522611)
1958
49
Hypophosphatasia. (13410963)
1957
50
Treatment of hypophosphatasia with cortisone. (13320804)
1956

Genetic Variations for Hypophosphatasia

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Expression for genes affiliated with Hypophosphatasia

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Hypophosphatasia

Search GEO for disease gene expression data for Hypophosphatasia.

Pathways for genes affiliated with Hypophosphatasia

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37NCBI BioSystems Database, 29KEGG, 12EMD Millipore, 53Reactome
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Pathways related to Hypophosphatasia according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.8RUNX2, ENPP1, ALPL
28.8ALPL, ALPP, ALPPL2, ALPI
3
NAD metabolism
Hide members
8.5ENPP1, ALPL, ALPP, ALPPL2, ALPI
4
Hide members
8.3PNPO, ENPP1, ALPL, ALPP, ALPPL2, ALPI

Compounds for genes affiliated with Hypophosphatasia

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44Novoseek, 49PharmGKB, 11DrugBank, 59Tocris Bioscience, 28IUPHAR, 2BitterDB, 24HMDB
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Compounds related to Hypophosphatasia according to GeneCards/GeneDecks:

(show top 50)    (show all 64)
idCompoundScoreTop Affiliating Genes
1fluorides4410.2CALCA, DSPP
2strontium ranelate4410.1CALCA, RUNX2
3calcium carbonate4410.0CALCA, DSPP, ALPP
4sodium fluoride4410.0ALPP, DSPP, CALCA
5vitamin b64410.0PNPO, ALPL, ALPP
6polycaprolactone4410.0ALPP, RUNX2
7pmma4410.0CALCA, ALPP, DSPP
8pyridoxal 5-phosphate449.9ALPP, ALPL, PNPO
9etidronic acid44 49 1111.9CALCA, ALPP
10ipriflavone449.9CALCA, ALPP, SLPI
11etidronate449.9ALPP, SLPI, CALCA
12vitamin k2449.8CALCA, SLPI, ALPP
13phosphoethanolamine449.8ALPI, ALPP, ALPL
14risedronate44 59 49 28 1113.8ALPP, CALCA, SLPI
15titanium449.8ALPP, SLPI, RUNX2
16amifostine44 1110.8ALPPL2, ALPL, ENPP1
17pyridinoline449.8ALPP, SLPI, CALCA
18zoledronic acid449.7SLPI, CALCA, ALPP
19alizarin449.7SLPI, RUNX2, ALPL, ALPP
2025-hydroxyvitamin d449.7SLPI, CALCA, ALPP
21creatinine449.7ALPP, CCL27, SLPI
22phosphorus449.7SLPI, CALCA, ALPP
23tartrate449.7CALCA, DSPP, SLPI, ALPP
24fluoride449.7SLPI, DSPP, ALPP, CALCA
25p-nitrophenyl phosphate449.6ALPI, ALPP, SLPI
26hydrocortisone44 2 59 1112.5IL1R1, ALPP, SLPI, CALCA
27calcitriol44 59 11 2412.4SLPI, CALCA, DSPP, ALPP
28alendronate44 49 1111.4CALCA, ALPP, DSPP, RUNX2, SLPI
29cellulose acetate449.4IL1R1, SLPI, ALPP, ALPI
30pyrophosphate44 2410.4ALPP, ALPL, ENPP1, RUNX2, ANKH
31ascorbic acid44 2410.4RUNX2, IL1R1, DSPP, SLPI, ALPP
32levamisole44 1110.4ALPPL2, ALPL, SLPI, ALPP
33hydroxyproline44 11 2411.3KHDRBS3, SLPI, ALPP, CALCA
34guanidine hydrochloride449.3ALPP, DSPP, ALPI
357,8-dihydroneopterin44 2410.2ALPP, ALPPL2, ALPI, ALPL
36dihydroxyacetone44 2410.2ALPP, ALPI, ALPPL2, ALPL
37dihydroneopterin triphosphate44 2410.2ALPPL2, ALPP, ALPI, ALPL
38lactate449.2DSPP, CALCA, SLPI, ALPP, IL1R1
39deoxypyridinoline449.0CCL27, SLPI, KHDRBS3, ALPP, CALCA
40vitamin d449.0DSPP, IL1R1, RUNX2, ALPL, ALPP, SLPI
41aspartate448.9DSPP, CCL27, ALPP, ALPL, SLPI
42pge2448.9CCL27, RUNX2, CALCA, IL1R1, SLPI, ALPP
43dexamethasone44 49 28 1111.8RUNX2, DSPP, IL1R1, SLPI, ENPP1, ALPP
44estrogen448.7SLPI, IL1R1, DSPP, CALCA, RUNX2, ALPP
45butyrate448.7RUNX2, ALPP, ALPPL2, ALPI, SLPI
46alanine448.5IL1R1, ALPP, KHDRBS3, DSPP, CCL27, RUNX2
47cyclic amp44 249.4RUNX2, CALCA, SLPI, ALPPL2, ENPP1
48magnesium44 11 2410.1ALPL, SLPI, ALPP, ALPPL2, IL1R1, PHOSPHO1
49hydroxyapatite448.0ANKH, CCL27, RUNX2, SLPI, ENPP1, ALPP
50calcium44 49 11 249.7CCL27, RUNX2, DSPP, ANKH, ALPI, ALPP

GO Terms for genes affiliated with Hypophosphatasia

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16Gene Ontology
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Cellular components related to Hypophosphatasia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1anchored to membraneGO:0312258.8ALPI, ALPPL2, ALPP, ALPL

Biological processes related to Hypophosphatasia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1biomineral tissue developmentGO:03121410.0ENPP1, DSPP
2negative regulation of ossificationGO:0302799.8CALCA, ENPP1
3endochondral ossificationGO:0019589.6ALPL, PHOSPHO1, RUNX2
4regulation of bone mineralizationGO:0305009.5ENPP1, ANKH, PHOSPHO1
5skeletal system developmentGO:0015019.4ALPL, ANKH, DSPP

Molecular functions related to Hypophosphatasia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1pyrophosphatase activityGO:0164629.8ALPL, PHOSPHO1
2alkaline phosphatase activityGO:0040358.5ALPI, ALPPL2, ALPP, ALPL

Products for genes affiliated with Hypophosphatasia

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  • Antibodies
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Sources for Hypophosphatasia

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet