Hypophosphatasia, Childhood malady

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

Aliases & Classifications for Hypophosphatasia, Childhood

About this section
11Disease Ontology, 12diseasecard, 13DISEASES, 23GeneReviews, 24GeneTests, 25Genetics Home Reference, 27GTR, 30ICD10, 31ICD10 via Orphanet, 37MedGen, 39MeSH, 40MESH via Orphanet, 45NCIt, 48NIH Rare Diseases, 50Novoseek, 52OMIM, 54Orphanet, 62SNOMED-CT, 64The Human Phenotype Ontology, 68UMLS, 69UMLS via Orphanet, 70UniProtKB/Swiss-Prot
See all MalaCards sources

Aliases & Descriptions for Hypophosphatasia, Childhood:

Name: Hypophosphatasia, Childhood 52 12 50 39
Hypophosphatasia 11 23 48 24 25 54 27 50 39 13 68
Childhood Hypophosphatasia 11 48 68
Phosphoethanolaminuria 48 25 54
Childhood-Onset Phosphoethanolaminuria 48 54
Deficiency of Alkaline Phosphatase 11 25
Childhood-Onset Hypophosphatasia 48 54
Childhood-Onset Rathburn Disease 48 54
Hypophosphatasia Childhood Type 70 27
Rathburn Disease 48 54
Hereditary Pyropoikilocytosis 68
Hypophospatasia, Childhood 11
Infantile Hypophosphatasia 68
Phosphoethanol-Aminuria 48
Hypophosphatasia, Mild 50
Hypophosphatasia Mild 48
Hopsc 70
Hpp 54


Orphanet epidemiological data:

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


hypophosphatasia, childhood:
Inheritance: autosomal recessive inheritance


External Ids:

OMIM52 241510
Disease Ontology11 DOID:14213
ICD1030 E83.39
NCIt45 C26798
MESH via Orphanet40 D007014
UMLS via Orphanet69 C0020630, C0220743
ICD10 via Orphanet31 E83.3
MedGen37 C0220743

Summaries for Hypophosphatasia, Childhood

About this section
NIH Rare Diseases:48 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, Childhood, also known as 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, Childhood is ALPL (Alkaline Phosphatase, Liver/Bone/Kidney), and among its related pathways are Folate biosynthesis and Osteoblast Signaling. Affiliated tissues include bone and skin, and related mouse phenotypes are respiratory system and craniofacial.

Genetics Home Reference:25 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.

OMIM:52 Hypophosphatasia is an inborn error of metabolism characterized clinically by defective bone mineralization and... (241510) more...

UniProtKB/Swiss-Prot:70 Hypophosphatasia childhood type: A bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase.

GeneReviews for NBK1150

Related Diseases for Hypophosphatasia, Childhood

About this section

Diseases related to Hypophosphatasia, Childhood via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 61)
idRelated DiseaseScoreTop Affiliating Genes
1hypophosphatasia, infantile34.1ALPL, ALPP
2hypophosphatasia, adult12.3
3prenatal benign hypophosphatasia11.8
5pleomorphic adenoma carcinoma10.4ALPL, ANKH
6diaphragmatic eventration10.4ALPP, DSPP
7anterolateral myocardial infarction10.4ALPL, ALPP
8camptodactyly with muscular hypoplasia, skeletal dysplasia, and abnormal palmar creases10.4DLX3, DSPP
9spinocerebellar ataxia, autosomal recessive 1810.3DSPP, SPP1
10spinal cancer10.3DSPP, SPP1
11depressed scar10.2DSPP, SPP1
12urethra leiomyoma10.2DLX3, DSPP
13anaerobic meningitis10.2DSPP, SPP1
14opthalmomandibulomelic dysplasia10.2ENPP1, PTH
15retinal vasculitis10.2ALPL, ANKH, ENPP1
16osteogenesis imperfecta, type iii10.1COL1A1, DSPP
18commensal bacterial infectious disease10.1ENPP1, PTH
19leukodystrophy10.0ALPL, PTH
20tuberous sclerosis-110.0ENPP1, PTH
21status epilepticus10.0ENPP1, SPP1
22protein-losing enteropathy10.0ALPL, ENPP1, PTH
23vulvovaginal candidiasis9.9ALPL, ANKH, COL1A1
24cleidocranial dysplasia9.9
26osteogenesis imperfecta9.9
29diabetic foot ulcers9.8COL1A1, DSPP, SPP1
30arterial calcification, generalized, of infancy, 29.8ALPL, ANKH, ENPP1, SPP1
31maxillary sinusitis9.8ANKH, COL1A1
33renal osteodystrophy9.8
36periodontal disease9.8
39physical disorder9.6COL1A1, PTH, SPP1
41chronic recurrent multifocal osteomyelitis9.6
42west syndrome9.6
47retinitis pigmentosa9.6

Graphical network of the top 20 diseases related to Hypophosphatasia, Childhood:

Diseases related to hypophosphatasia, childhood

Symptoms & Phenotypes for Hypophosphatasia, Childhood

About this section

Symptoms by clinical synopsis from OMIM:


Clinical features from OMIM:


Human phenotypes related to Hypophosphatasia, Childhood:

 64 54 (show all 35)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormality of the teeth64 54 hallmark (90%) Very frequent (99-80%) HP:0000164
2 abnormality of the ribs64 54 hallmark (90%) Very frequent (99-80%) HP:0000772
3 narrow chest64 54 hallmark (90%) Very frequent (99-80%) HP:0000774
4 abnormality of the metaphyses64 54 hallmark (90%) Very frequent (99-80%) HP:0000944
5 craniosynostosis64 54 hallmark (90%) Very frequent (99-80%) HP:0001363
6 emphysema64 54 hallmark (90%) Very frequent (99-80%) HP:0002097
7 short stature64 54 hallmark (90%) Very frequent (99-80%) HP:0004322
8 bowing of the long bones64 54 hallmark (90%) Very frequent (99-80%) HP:0006487
9 sacrococcygeal pilonidal abnormality64 hallmark (90%) HP:0010767
10 behavioral abnormality64 typical (50%) HP:0000708
11 seizures64 54 typical (50%) Frequent (79-30%) HP:0001250
12 muscular hypotonia64 54 typical (50%) Frequent (79-30%) HP:0001252
13 anemia64 54 typical (50%) Frequent (79-30%) HP:0001903
14 respiratory insufficiency64 54 typical (50%) Frequent (79-30%) HP:0002093
15 recurrent fractures64 54 typical (50%) Frequent (79-30%) HP:0002757
16 hypercalcemia64 54 typical (50%) Frequent (79-30%) HP:0003072
17 dolichocephaly64 HP:0000268
18 proptosis64 HP:0000520
19 carious teeth64 HP:0000670
20 rachitic rosary64 HP:0000897
21 skin dimple over apex of long bone angulation64 54 Very frequent (99-80%) HP:0001024
22 frontal bossing64 HP:0002007
23 waddling gait64 HP:0002515
24 bowing of the legs64 HP:0002979
25 myopathy64 HP:0003198
26 phosphoethanolaminuria64 HP:0003239
27 low alkaline phosphatase64 HP:0003282
28 elevated urine pyrophosphate64 HP:0003491
29 premature loss of primary teeth64 HP:0006323
30 elevated plasma pyrophosphate64 HP:0011864
31 large fontanelles54 Very frequent (99-80%)
32 irritability54 Frequent (79-30%)
33 failure to thrive in infancy54 Very frequent (99-80%)
34 feeding difficulties in infancy54 Very frequent (99-80%)
35 skin dimples54 Very frequent (99-80%)

UMLS symptoms related to Hypophosphatasia, Childhood:

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

MGI Mouse Phenotypes related to Hypophosphatasia, Childhood according to GeneCards Suite gene sharing:

idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053889.2ALPL, ANKH, COL1A1, SPP1, SPTA1
2MP:00053829.1ALPL, ANKH, COL1A1, PTH, SPP1
3MP:00053878.4ALPL, ANKH, COL1A1, ENPP1, PTH, SPP1
4MP:00053858.0ALPL, ANKH, COL1A1, DLX3, ENPP1, PTH
5MP:00053788.0ALPL, ANKH, COL1A1, DLX3, ENPP1, PTH
6MP:00053907.6ALPL, ANKH, COL1A1, ENPP1, PTH, SPP1

Drugs & Therapeutics for Hypophosphatasia, Childhood

About this section

Drugs for Hypophosphatasia, Childhood (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

idNameStatusPhaseClinical TrialsCas NumberPubChem Id
1ImmunoglobulinsPhase 4, Phase 2, Phase 16045
2Immunoglobulin GPhase 4, Phase 2, Phase 1265
3AntibodiesPhase 4, Phase 2, Phase 16045

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
4Safety and Efficacy of Asfotase Alfa in Patients With Hypophosphatasia (HPP)CompletedNCT02456038Phase 2
5Dose Escalation Study to Evaluate the Safety and Tolerability of Multiple Infusions of BPS804 in Adults With Hypophosphatasia (HPP)CompletedNCT01406977Phase 2
6Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)CompletedNCT01205152Phase 2
7Extension Study of Protocol ENB-006-09 - Study of Asfotase Alfa in Children With Hypophosphatasia (HPP)CompletedNCT01203826Phase 2
8Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)CompletedNCT00744042Phase 1, Phase 2
9Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)CompletedNCT00952484Phase 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
16Burden of Disease in Hypophosphatasia (HPP)CompletedNCT02291497
17Non-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
18Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at SanfordRecruitingNCT01793168
19Natural History Study of Patients With Hypophosphatasia (HPP)RecruitingNCT02237625
20Biomarker for Hypophosphatasia DiseaseRecruitingNCT02603042
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, Childhood

Cochrane evidence based reviews: hypophosphatasia

Genetic Tests for Hypophosphatasia, Childhood

About this section

Genetic tests related to Hypophosphatasia, Childhood:

id Genetic test Affiliating Genes
1 Hypophosphatasia27 24 ALPL
2 Childhood Hypophosphatasia27

Anatomical Context for Hypophosphatasia, Childhood

About this section

MalaCards organs/tissues related to Hypophosphatasia, Childhood:

Bone, Skin

Publications for Hypophosphatasia, Childhood

About this section

Variations for Hypophosphatasia, Childhood

About this section

UniProtKB/Swiss-Prot genetic disease variations for Hypophosphatasia, Childhood:

id Symbol AA change Variation ID SNP ID

Clinvar genetic disease variations for Hypophosphatasia, Childhood:

5 (show all 28)
id Gene Variation Type Significance SNP ID Assembly Location
1SPTA1NM_003126.2(SPTA1): c.135G> T (p.Arg45Ser)SNVPathogenicrs121918637GRCh37Chr 1, 158655027: 158655027
2SPTA1NM_003126.2(SPTA1): c.82C> A (p.Arg28Ser)SNVPathogenicrs121918642GRCh37Chr 1, 158655080: 158655080
3SPTA1NM_003126.2(SPTA1): c.82C> T (p.Arg28Cys)SNVPathogenicrs121918642GRCh37Chr 1, 158655080: 158655080
4SPTA1NM_003126.2(SPTA1): c.83G> A (p.Arg28His)SNVPathogenicrs121918641GRCh37Chr 1, 158655079: 158655079
5SPTA1NM_003126.2(SPTA1): c.620T> C (p.Leu207Pro)SNVPathogenicrs121918643GRCh37Chr 1, 158650431: 158650431
6SPTA1NM_003126.2(SPTA1): c.2373C> A (p.Asp791Glu)SNVPathogenicrs7418956GRCh37Chr 1, 158632583: 158632583
7ALPLNM_000478.5(ALPL): c.535G> A (p.Ala179Thr)SNVLikely pathogenic, Pathogenicrs121918000GRCh37Chr 1, 21890596: 21890596
8ALPLNM_000478.5(ALPL): c.211C> T (p.Arg71Cys)SNVPathogenicrs121918001GRCh37Chr 1, 21887619: 21887619
9ALPLNM_000478.5(ALPL): c.881A> C (p.Asp294Ala)SNVPathogenicrs121918002GRCh37Chr 1, 21900176: 21900176
10ALPLNM_000478.5(ALPL): c.212G> C (p.Arg71Pro)SNVPathogenicrs121918003GRCh37Chr 1, 21887620: 21887620
11ALPLNM_000478.5(ALPL): c.620A> C (p.Gln207Pro)SNVPathogenicrs121918004GRCh37Chr 1, 21890681: 21890681
12ALPLNM_000478.5(ALPL): c.98C> T (p.Ala33Val)SNVPathogenicrs121918005GRCh37Chr 1, 21887155: 21887155
13ALPLNM_000478.5(ALPL): c.1306T> C (p.Tyr436His)SNVPathogenicrs121918006GRCh37Chr 1, 21903131: 21903131
14ALPLNM_000478.5(ALPL): c.892G> A (p.Glu298Lys)SNVPathogenicrs121918017GRCh37Chr 1, 21900187: 21900187
15ALPLNM_000478.5(ALPL): c.571G> A (p.Glu191Lys)SNVPathogenicrs121918007GRCh37Chr 1, 21890632: 21890632
16ALPLNM_000478.5(ALPL): c.1133A> T (p.Asp378Val)SNVPathogenicrs121918008GRCh37Chr 1, 21902361: 21902361
17ALPLNM_000478.5(ALPL): c.1001G> A (p.Gly334Asp)SNVLikely pathogenic, Pathogenicrs121918009GRCh37Chr 1, 21902229: 21902229
18ALPLNM_000478.5(ALPL): c.979T> C (p.Phe327Leu)SNVLikely pathogenic, Pathogenicrs121918010GRCh37Chr 1, 21900274: 21900274
19ALPLNM_000478.5(ALPL): c.1559delT (p.Leu520Argfs)deletionPathogenicrs387906525GRCh37Chr 1, 21904125: 21904125
20ALPLNM_000478.5(ALPL): c.407G> A (p.Arg136His)SNVLikely pathogenic, Pathogenicrs121918011GRCh37Chr 1, 21889712: 21889712
21ALPLNM_000478.5(ALPL): c.485G> T (p.Gly162Val)SNVPathogenicrs121918012GRCh37Chr 1, 21890546: 21890546
22ALPLNM_000478.5(ALPL): c.346G> A (p.Ala116Thr)SNVLikely pathogenic, Pathogenicrs121918013GRCh37Chr 1, 21889651: 21889651
23ALPLNM_000478.5(ALPL): c.1250A> G (p.Asn417Ser)SNVLikely pathogenic, Pathogenicrs121918014GRCh37Chr 1, 21903075: 21903075
24ALPLNM_000478.5(ALPL): c.1366G> A (p.Gly456Arg)SNVPathogenicrs121918016GRCh37Chr 1, 21903932: 21903932
25ALPLNM_000478.5(ALPL): c.746G> T (p.Gly249Val)SNVPathogenicrs121918018GRCh37Chr 1, 21894694: 21894694
26ALPLNM_000478.5(ALPL): c.526G> A (p.Ala176Thr)SNVPathogenicrs121918019GRCh37Chr 1, 21890587: 21890587
27ALPLNM_000478.5(ALPL): c.814C> T (p.Arg272Cys)SNVPathogenicrs121918020GRCh37Chr 1, 21896819: 21896819
28ALPLNM_000478.5(ALPL): c.400_401delACinsCA (p.Thr134His)indelLikely pathogenic, Pathogenicrs786204530GRCh38Chr 1, 21563212: 21563213

Expression for genes affiliated with Hypophosphatasia, Childhood

About this section
Search GEO for disease gene expression data for Hypophosphatasia, Childhood.

Pathways for genes affiliated with Hypophosphatasia, Childhood

About this section

GO Terms for genes affiliated with Hypophosphatasia, Childhood

About this section

Cellular components related to Hypophosphatasia, Childhood according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1proteinaceous extracellular matrixGO:00055789.3ALPL, COL1A1, DSPP
2extracellular spaceGO:00056158.9ALPL, COL1A1, ENPP1, PTH, SPP1

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

(show all 10)
idNameGO IDScoreTop Affiliating Genes
1inorganic diphosphate transportGO:003050510.4ANKH, ENPP1
2regulation of bone mineralizationGO:003050010.3ANKH, ENPP1
3endochondral ossificationGO:000195810.2ALPL, COL1A1
4blood vessel developmentGO:000156810.1COL1A1, DLX3
5biomineral tissue developmentGO:003121410.0DSPP, ENPP1, SPP1
6response to steroid hormoneGO:004854510.0COL1A1, SPP1
7response to vitamin DGO:00332809.8ALPL, PTH, SPP1
8osteoblast differentiationGO:00016499.7ALPL, COL1A1, SPP1
9extracellular matrix organizationGO:00301989.7COL1A1, DSPP, SPP1
10skeletal system developmentGO:00015018.4ALPL, ANKH, COL1A1, DSPP, PTH

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

idNameGO IDScoreTop Affiliating Genes
1alkaline phosphatase activityGO:00040359.9ALPL, ALPP

Sources for Hypophosphatasia, Childhood

About this section
31ICD10 via Orphanet
40MESH via Orphanet
53OMIM via Orphanet
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
69UMLS via Orphanet