HPP
MCID: HYP035
MIFTS: 66

Hypophosphatasia (HPP) malady

Bone, Fetal, Genetic categories

Summaries for Hypophosphatasia

Sources:
43NIH Rare Diseases, 21Genetics Home Reference, 64Wikipedia, 47OMIM, 19GeneReviews, 33MalaCards
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NIH Rare Diseases:43 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 hypophosphatasia, infantile and hepatitis c, and has symptoms including autosomal recessive inheritance, seizures/epilepsy/absences/spasms/status epilepticus and failure to thrive/difficulties for feeding in infancy/growth delay. 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 skin, liver and kidney, 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:64 Hypophosphatasia is a rare, and sometimes fatal metabolic bone disease. Clinical symptoms are... more...

Description from OMIM:47 241500,241510,146300

GeneReviews summary for hops

Aliases & Classifications for Hypophosphatasia

Sources:
61UMLS, 8Disease Ontology, 19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 10DISEASES, 45Novoseek, 49Orphanet, 9diseasecard, 47OMIM, 57SNOMED-CT, 35MeSH, 40NCIt, 36MESH via Orphanet, 26ICD10 via Orphanet, 58SNOMED-CT via Orphanet, 62UMLS via Orphanet
See all sources

Classifications:

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


Characteristics (Orphanet epidemiological data):

49
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 43 20 22 21 10 45 49 61
hypophosphatasia, childhood 9 47 45
childhood hypophosphatasia 8 43 61
deficiency of alkaline phosphatase 8 21
hypophosphatasia childhood 43 22
phosphoethanolaminuria 21 49
autosomal recessive hypophosphatemic bone disease 61
hyperpigmentation, familial progressive 61
childhood-onset phosphoethanolaminuria 49
childhood-onset hypophosphatasia 49
childhood-onset rathburn disease 49
hypokalemic periodic paralysis 61
hypophospatasia, childhood 8
infantile hypophosphatasia 61
phosphoethanol-aminuria 43
hypophosphatasia, mild 45
hypophosphatasia mild 43
rathburn disease 49
hypopp 19
hokpp 19
hhrh 43
hpp 49


External Ids:

Disease Ontology8 DOID:14213
MeSH35 D007014
NCIt40 C26798
MESH via Orphanet36 D007014
ICD10 via Orphanet26 E83.3
SNOMED-CT via Orphanet58 190859005, 360792001, 30174008
UMLS via Orphanet62 C0020630, C0220743

Related Diseases for Hypophosphatasia

Sources:
17GeneCards, 18GeneDecks
See all sources

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

(show top 50)    (show all 137)
idRelated DiseaseScoreTop Affiliating Genes
1hypophosphatasia, infantile31.1ALPL, ALPP
2hepatitis c30.3IL1R1
3thyroiditis30.3CALCA
4hypercalcemia30.3ALPL, SLPI, CALCA, ALPPL2, ALPP
5osteogenesis imperfecta30.2ALPP, ALPPL2, DSPP, ALPL
6cleidocranial dysplasia30.2RUNX2, ALPL
7arthropathy30.1ALPL, ANKH
8renal osteodystrophy30.1CALCA, SLPI, ALPP, ALPPL2, ALPL
9hyperphosphatemia29.9ALPP, ALPPL2, ALPL, SLPI, RUNX2
10hypophosphatemia29.9ALPPL2, ALPP, ALPL, DSPP, CALCA
11osteomalacia29.9SLPI, ALPL, ALPPL2, CALCA, ALPP
12osteoarthritis29.8ENPP1, CALCA, RUNX2, SLPI, IL1R1, ANKH
13hypokalemic periodic paralysis11.5
14thyrotoxic periodic paralysis11.1
15hypophosphatasia, adult10.8
16renal tubular acidosis10.7
17thyrotoxicosis10.7
18hypokalemic periodic paralysis type 110.7
19graves' disease10.5
20renal tubular acidosis, distal10.5
21hypokalemic periodic paralysis type 210.5
22malignant hyperthermia10.5
23sjogren's syndrome10.4
24gitelman syndrome10.4
25hypokalemia10.4
26adenoma10.4
27thyrotoxic periodic paralysis 110.4
28hereditary hypophosphatemic rickets with hypercalciuria10.3
29autism 1910.3
30pyropoikilocytosis10.3
31hyperpigmentation, familial progressive, 210.3
32hyperpigmentation, familial progressive, 110.3
33hyperkalemic periodic paralysis type 210.2
34membranoproliferative glomerulonephritis10.2
35wolff-parkinson-white syndrome10.2
36hyperuricemia10.2
37andersen-tawil syndrome10.2
38superior mesenteric artery syndrome10.2
39diabetes insipidus10.2
40amelogenesis imperfecta10.2
41tropical sprue10.2
42gynecomastia10.2
43hyperkalemic periodic paralysis10.2
44nephrogenic diabetes insipidus10.2
45hepatitis a10.2
46hypomyelination and congenital cataract10.2
47bidirectional tachycardia10.2
48growth hormone deficiency10.2
49westphal disease10.2
50thymic hyperplasia10.2

Graphical network of the top 20 diseases related to Hypophosphatasia:



Diseases related to hypophosphatasia

Clinical Features for Hypophosphatasia

Sources:
47OMIM, 49Orphanet
See all sources

Clinical features from OMIM:

241500,241510,146300

Clinical synopsis from OMIM:

241510

Symptoms:

49 (show all 20)
  • autosomal recessive inheritance
  • 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
  • narrow rib cage/thorax
  • mutiple fractures/bone fragility
  • stillbirth/neonatal death
  • large fontanelle/delayed fontanelle closure
  • craniostenosis/craniosynostosis/sutural synostosis
  • hypercalcemia
  • dermoid sinus/dimple/pit (excluding sacral)

Drugs & Therapeutics for Hypophosphatasia

Sources:
5CenterWatch, 42NIH Clinical Center, 6ClinicalTrials, 61UMLS, 41NDF-RT
See all sources

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

Sources:
20GeneTests, 22GTR
See all sources

Genetic tests related to Hypophosphatasia:

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

Anatomical Context for Hypophosphatasia

Sources:
33MalaCards
See all sources

MalaCards organs/tissues related to Hypophosphatasia:

33
Skin, Liver, Kidney, Bone marrow, Whole blood, T cells, Endothelial, Fetal liver

Animal Models for Hypophosphatasia or affiliated genes

Sources:
37MGI, 28inGenious Targeting Laboratory
See all sources

Publications for Hypophosphatasia

Sources:
51PubMed
See all sources

Articles related to Hypophosphatasia:

(show top 50)    (show all 450)
idTitleAuthorsYear
1
Infantile hypophosphatasia without bone deformities presenting with severe pyridoxine-resistant seizures. (24100244)
2013
2
Compound heterozygosity of two functional null mutations in the ALPL gene associated with deleterious neurological outcome in an infant with hypophosphatasia. (23454488)
2013
3
Therapy-related Ph+ leukemia after both bone marrow and mesenchymal stem cell transplantation for hypophosphatasia. (23782379)
2013
4
An unusual stress fracture in an archer with hypophosphatasia. (24383027)
2013
5
Evolutionary analysis of ALPL validates and predicts human mutations leading to hypophosphatasia. (24134978)
2012
6
Respiratory mechanics in an infant with perinatal lethal hypophosphatasia treated with human recombinant enzyme replacement therapy. (22328548)
2012
7
Enzyme replacement therapy in different clinical phenotypes of hypophosphatasia--presentation of two cases. (24134990)
2012
8
Rescue of severe infantile hypophosphatasia mice by AAV-mediated sustained expression of soluble alkaline phosphatase. (21388343)
2011
9
Neurosurgical aspects of childhood hypophosphatasia. (18769927)
2009
10
Specific ultrasonographic features of perinatal lethal hypophosphatasia. (18386808)
2008
11
Autosomal recessive hypophosphatasia manifesting in utero with long bone deformity but showing spontaneous postnatal improvement. (18559907)
2008
12
Intramedullary nailing for adult hypophosphatasia: a case report. (19126913)
2008
13
Mutations of the tissue non-specific alkaline phosphatase gene (TNAP) causing a non-lethal case of perinatal hypophosphatasia. (17409132)
2007
14
Low serum alkaline phosphatase activity and pathologic fracture: case report and brief review of hypophosphatasia diagnosed in adulthood. (17229666)
2006
15
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
16
Hypophosphatasia: report of two affected girls with spontaneous improvement of skeletal defects]. (16583935)
2005
17
The mutant (F310L and V365I) tissue-nonspecific alkaline phosphatase gene from hypophosphatasia. (15137467)
2004
18
A successful treatment with pyridoxal phosphate for West syndrome in hypophosphatasia. (15033207)
2004
19
Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions. (11999978)
2002
20
A molecular approach to dominance in hypophosphatasia. (11479741)
2001
21
A light and scanning electron microscopic study of primary teeth in hypophosphatasia]. (11776910)
1999
22
Molecular diagnosis of hypophosphatasia with severe periodontitis. (10397525)
1999
23
Hypophosphatasia: the importance of alkaline phosphatase in bone mineralization. (10659574)
1999
24
Genetic analysis of hypophosphatasia. (9316305)
1997
25
Aberrant properties of alkaline phosphatase in patient fibroblasts correlate with clinical expressivity in severe forms of hypophosphatasia. (8675582)
1996
26
A clinical and research protocol for characterizing patients with hypophosphatasia. (8668564)
1996
27
Generalized odontodysplasia concomitant with mild hypophosphatasia--a case report. (8384047)
1993
28
Renal osteodystrophy, disorders of vitamin D metabolism, and hypophosphatasia. (1599820)
1992
29
A case of severe periodontal disease in adolescence associated with hypophosphatasia]. (1955807)
1991
30
Hypophosphatasemia, not hypophosphatasia. (1920324)
1991
31
Prenatal follow-up of hypophosphatasia by ultrasound: case report. (2178994)
1990
32
Accumulation of phosphorus compounds in tissues and cultured skin fibroblasts in patients with hypophosphatasia. (3408505)
1988
33
Infantile hypophosphatasia--linkage with the RH locus. (3128473)
1987
34
Imaging case of the month. Hypophosphatasia. (3893454)
1985
35
Hyperphosphataemia in hypophosphatasia. (4088394)
1985
36
Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease. (7108657)
1982
37
Fifty-year follow-up of hypophosphatasia. (7305584)
1981
38
Alkaline phosphatase induction in fibroblast cultures: prenatal diagnosis and carrier detection in hypophosphatasia. (723908)
1978
39
Prenatal diagnosis of hypophosphatasia; genetic, biochemical, and clinical studies. (677124)
1978
40
Hypophosphatasia. (5020955)
1972
41
Intestinal alkaline phosphatase activity in familial hypophosphatasia. (4296721)
1968
42
Hypophosphatasia in an adult. (4291188)
1967
43
Radiological and microradiographic features in a case of congenital hypophosphatasia. (4288487)
1966
44
BAND KERATOPATHY AND CONJUNCTIVAL CALCIFICATION IN HYPOPHOSPHATASIA. (14109032)
1964
45
Ethanolamine phosphate excretion in a family with hypophosphatasia. (13949647)
1963
46
Distribution of alkaline phosphatase in the serum proteins in hypophosphatasia. (14458464)
1962
47
Hypophosphatasia: a genetic study. (14490519)
1961
48
An unusual case of kyphotic paraplegia and hypophosphatasia. (13745221)
1960
49
Hypophosphatasia with congenital dimples. (13843859)
1959
50
The identification of a ninhydrin-positive urinary component recently reported in hypophosphatasia. (13479812)
1957

Genetic Variations for Hypophosphatasia

Expression for genes affiliated with Hypophosphatasia

Sources:
1BioGPS, 15Gene Expression Omnibus DataSets
See all sources
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

Sources:
38NCBI BioSystems Database, 30KEGG, 12EMD Millipore, 54Reactome
See all sources

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

Sources:
45Novoseek, 50PharmGKB, 11DrugBank, 60Tocris Bioscience, 29IUPHAR, 2BitterDB, 24HMDB
See all sources

Compounds related to Hypophosphatasia according to GeneCards/GeneDecks:

(show top 50)    (show all 64)
idCompoundScoreTop Affiliating Genes
1fluorides4510.2DSPP, CALCA
2strontium ranelate4510.1RUNX2, CALCA
3calcium carbonate4510.0CALCA, DSPP, ALPP
4sodium fluoride4510.0CALCA, DSPP, ALPP
5vitamin b64510.0PNPO, ALPL, ALPP
6pmma4510.0ALPP, DSPP, CALCA
7etidronic acid45 50 1111.9CALCA, ALPP
8pyridoxal 5-phosphate459.9ALPP, ALPL, PNPO
9polycaprolactone459.9RUNX2, ALPP
10ipriflavone459.9CALCA, SLPI, ALPP
11etidronate459.9CALCA, SLPI, ALPP
12vitamin k2459.8ALPP, SLPI, CALCA
13phosphoethanolamine459.8ALPL, ALPP, ALPI
14risedronate45 60 50 29 1113.8CALCA, SLPI, ALPP
15titanium459.8ALPP, SLPI, RUNX2
16amifostine45 1110.8ALPPL2, ALPL, ENPP1
17pyridinoline459.8CALCA, SLPI, ALPP
18zoledronic acid459.7ALPP, SLPI, CALCA
19alizarin459.7ALPP, ALPL, SLPI, RUNX2
2025-hydroxyvitamin d459.7ALPP, SLPI, CALCA
21creatinine459.7ALPP, SLPI, CCL27
22phosphorus459.7CALCA, SLPI, ALPP
23tartrate459.7CALCA, DSPP, SLPI, ALPP
24fluoride459.7ALPP, SLPI, DSPP, CALCA
25p-nitrophenyl phosphate459.6SLPI, ALPP, ALPI
26hydrocortisone45 2 60 1112.5CALCA, IL1R1, SLPI, ALPP
27calcitriol45 60 11 2412.4CALCA, DSPP, SLPI, ALPP
28alendronate45 50 1111.4RUNX2, CALCA, DSPP, SLPI, ALPP
29cellulose acetate459.4ALPI, ALPP, SLPI, IL1R1
30pyrophosphate45 2410.4RUNX2, ANKH, ENPP1, ALPL, ALPP
31ascorbic acid45 2410.4RUNX2, DSPP, IL1R1, SLPI, ALPP
32levamisole45 1110.4ALPPL2, ALPP, ALPL, SLPI
33hydroxyproline45 11 2411.3ALPP, SLPI, KHDRBS3, CALCA
34guanidine hydrochloride459.3DSPP, ALPP, ALPI
357,8-dihydroneopterin45 2410.2ALPL, ALPP, ALPPL2, ALPI
36dihydroneopterin triphosphate45 2410.2ALPL, ALPP, ALPPL2, ALPI
37dihydroxyacetone45 2410.2ALPL, ALPP, ALPPL2, ALPI
38lactate459.2CALCA, DSPP, IL1R1, SLPI, ALPP
39deoxypyridinoline459.0CCL27, CALCA, KHDRBS3, SLPI, ALPP
40vitamin d459.0RUNX2, CALCA, DSPP, IL1R1, SLPI, ALPL
41aspartate458.9ALPP, ALPL, SLPI, DSPP, CCL27
42pge2458.9RUNX2, CCL27, CALCA, IL1R1, SLPI, ALPP
43dexamethasone45 50 29 1111.8RUNX2, CCL27, DSPP, IL1R1, SLPI, ENPP1
44estrogen458.7CALCA, DSPP, IL1R1, SLPI, ALPP, RUNX2
45butyrate458.7RUNX2, SLPI, ALPP, ALPPL2, ALPI
46alanine458.5RUNX2, CCL27, DSPP, IL1R1, KHDRBS3, SLPI
47cyclic amp45 249.4ALPPL2, ENPP1, SLPI, CALCA, RUNX2
48magnesium45 11 2410.1PHOSPHO1, IL1R1, SLPI, ALPL, ALPP, ALPPL2
49hydroxyapatite458.0ALPI, RUNX2, CCL27, DSPP, ANKH, SLPI
50calcium45 50 11 249.7ANKH, DSPP, CALCA, CCL27, RUNX2, IL1R1

GO Terms for genes affiliated with Hypophosphatasia

Sources:
16Gene Ontology
See all sources

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:0302799.8ENPP1, CALCA
3endochondral ossificationGO:0019589.6ALPL, PHOSPHO1, RUNX2
4regulation of bone mineralizationGO:0305009.5PHOSPHO1, ANKH, ENPP1
5skeletal system developmentGO:0015019.4ALPL, DSPP, ANKH

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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Sources for Hypophosphatasia

3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
61UMLS
62UMLS via Orphanet