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 stillbirth/neonatal death, hypercalcemia and anaemia. 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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60UMLS, 8Disease Ontology, 19GeneReviews, 42NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 10DISEASES, 44Novoseek, 48Orphanet, 9diseasecard, 46OMIM, 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)
  • stillbirth/neonatal death
  • hypercalcemia
  • anaemia
  • mutiple fractures/bone fragility
  • psychic/behavioural troubles
  • seizures/epilepsy/absences/spasms/status epilepticus
  • hypotonia
  • 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
  • craniostenosis/craniosynostosis/sutural synostosis

Drugs & Therapeutics for Hypophosphatasia

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Sources:
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, Liver, Kidney, 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
Clinical spectrum of hypophosphatasia diagnosed in adults. (23352924)
2013
2
In silico scoring of ALPL gene mutations help to distinguish severe and moderate phenotypes in hypophosphatasia. (24134979)
2012
3
Physiological role of alkaline phosphatase explored in hypophosphatasia. (20392236)
2010
4
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. (19335222)
2009
5
New bone formation by allogeneic mesenchymal stem cell transplantation in a patient with perinatal hypophosphatasia. (19446101)
2009
6
Prosthetic rehabilitation of hypophosphatasia: a case report. (19918476)
2009
7
Hyperechoic metaphyses in hypophosphatasia: what does it mean? (18084754)
2008
8
Treatment of adult hypophosphatasia with teriparatide. (18308659)
2008
9
Therapy for hypophosphatasia]. (17906415)
2007
10
Prenatal genetic diagnosis of severe perinatal (lethal) hypophosphatasia. (17384481)
2007
11
Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. (16803637)
2006
12
Common mutations F310L and T1559del in the tissue-nonspecific alkaline phosphatase gene are related to distinct phenotypes in Japanese patients with hypophosphatasia. (15660230)
2005
13
Hypophosphatasia in Taiwan: report of two cases. (15875439)
2005
14
Autosomal recessive adult-onset hypophosphatasia. (16373239)
2005
15
Severe perinatal hypophosphatasia due to homozygous deletion of T at nucleotide 1559 in the tissue nonspecific alkaline phosphatase gene. (12975786)
2003
16
A case of hypophosphatasia. (14735810)
2003
17
Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia. (12424590)
2002
18
Adult hypophosphatasia. Current aspects. (11324927)
2001
19
Pyridoxine-induced photosensitivity and hypophosphatasia. (11146351)
2000
20
Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. (10620060)
1999
21
Intracellular retention and degradation of tissue-nonspecific alkaline phosphatase with a Gly317-->Asp substitution associated with lethal hypophosphatasia. (9618260)
1998
22
Detection of deletion 1154-1156 hypophosphatasia mutation using TNSALP exon amplification. (9192863)
1997
23
First-trimester prenatal molecular diagnosis of infantile hypophosphatasia in a Japanese family. (8809899)
1996
24
Hyperphosphatemia in infantile hypophosphatasia: implications for carrier diagnosis and screening. (2301398)
1990
25
Immunological study on hypophosphatasia. (2253404)
1990
26
Biochemical and morphological effects of human hepatic alkaline phosphatase in a neonate with hypophosphatasia. (2642253)
1989
27
First identification of a gene defect for hypophosphatasia: evidence that alkaline phosphatase acts in skeletal mineralization. (2605956)
1989
28
Prominent transverse (Bowdler) bone spurs as a diagnostic clue in a case of neonatal hypophosphatasia without metaphyseal irregularity. (2755749)
1989
29
Adult hypophosphatasia in a geriatric patient. (3339218)
1988
30
A missense mutation in the human liver/bone/kidney alkaline phosphatase gene causing a lethal form of hypophosphatasia. (3174660)
1988
31
Lethal osteogenesis imperfecta: abnormal collagen metabolism and biochemical characteristics of hypophosphatasia. (3181205)
1988
32
Hypophosphatasia: report of a case with unique oral manifestations. (3256598)
1988
33
Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism. (4031070)
1985
34
First trimester diagnosis of hypophosphatasia with a monoclonal antibody to the liver/bone/kidney isoenzyme of alkaline phosphatase. (2864577)
1985
35
Early prenatal diagnosis of congenital hypophosphatasia: case report. (3883342)
1985
36
Adult hypophosphatasia without apparent skeletal disease: "odontohypophosphatasia" in four heterozygote members of a family. (6727276)
1984
37
Enzyme replacement therapy for infantile hypophosphatasia attempted by intravenous infusions of alkaline phosphatase-rich Paget plasma: results in three additional patients. (6502342)
1984
38
Cranial manifestations of hypophosphatasia in childhood nephrotic syndrome. (6430833)
1984
39
Cholestatic jaundice with a normal serum alkaline phosphatase level: another case of hypophosphatasia in an adult. (6847845)
1983
40
Adult hypophosphatasia. (6648620)
1983
41
Prenatal diagnosis of congenital hypophosphatasia: challenge met most adequately by fetal radiography. (7163290)
1982
42
Hypophosphatasia in renal-transplant patients. (7008975)
1981
43
Two siblings with hypophosphatasia. (7415841)
1980
44
Neonatal hypophosphatasia. (A case report). (7251128)
1980
45
Hypophosphatasia. Review of 24 cases. (1012798)
1976
46
Prenatal diagnosis of hypophosphatasia. (58381)
1976
47
Hypophosphatasia associated with calcium pyrophosphate dihydrate deposits in cartilage. Report of a case. (4317094)
1970
48
EXCRETION OF INORGANIC PYROPHOSPHATE IN HYPOPHOSPHATASIA. (14337825)
1965
49
Apparent dominant inheritance of hypophosphatasia. (13912932)
1962
50
Hereditary enzymatic effects as illustrated by hypophosphatasia. (13627827)
1958

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
19.8ALPL, ENPP1, RUNX2
28.8ALPI, ALPPL2, ALPP, ALPL
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