HOPSC
MCID: HYP596
MIFTS: 43

Hypophosphatasia, Childhood (HOPSC)

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

Aliases & Classifications for Hypophosphatasia, Childhood

MalaCards integrated aliases for Hypophosphatasia, Childhood:

Name: Hypophosphatasia, Childhood 58 13 56
Childhood Hypophosphatasia 12 54 30 6 15 41 74
Childhood-Onset Phosphoethanolaminuria 54 60
Childhood-Onset Hypophosphatasia 54 60
Childhood-Onset Rathburn Disease 54 60
Hypophosphatasia Childhood Type 76
Hopsc 76

Characteristics:

Orphanet epidemiological data:

60
childhood-onset hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Childhood,Infancy;

OMIM:

58
Miscellaneous:
waddling gait
delayed onset of walking
presentation after 6 months

Inheritance:
autosomal recessive


HPO:

33
hypophosphatasia, childhood:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0110915
OMIM 58 241510
ICD10 via Orphanet 35 E83.3
UMLS via Orphanet 75 C0220743
Orphanet 60 ORPHA247667
MedGen 43 C0220743
UMLS 74 C0220743

Summaries for Hypophosphatasia, Childhood

NIH Rare Diseases : 54 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.

MalaCards based summary : Hypophosphatasia, Childhood, also known as childhood hypophosphatasia, is related to hypophosphatasia and hypophosphatasia, adult, and has symptoms including seizures and waddling gait. An important gene associated with Hypophosphatasia, Childhood is ALPL (Alkaline Phosphatase, Biomineralization Associated), and among its related pathways/superpathways are Metabolism of proteins and NAD metabolism. Affiliated tissues include bone and skin, and related phenotypes are frontal bossing and seizures

Disease Ontology : 12 A hypophosphatasia that has material basis in an autosomal recessive mutation of ALPL on chromosome 1p36.12.

OMIM : 58 Hypophosphatasia is an inborn error of metabolism characterized clinically by defective bone mineralization and biochemically by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Fraser (1957) classified forms of hypophosphatasia according to age of onset: perinatal (see 241500), infantile (241500), childhood, and adult (146300). Whyte (1988) indicated a fifth form of hypophosphatasia with primarily only dental manifestations, referred to as odontohypophosphatasia (see 241500). All of these forms are allelic. (241510)

UniProtKB/Swiss-Prot : 76 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.

Related Diseases for Hypophosphatasia, Childhood

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

(show all 14)
# Related Disease Score Top Affiliating Genes
1 hypophosphatasia 32.2 ALPL ALPP SPTA1
2 hypophosphatasia, adult 10.0 ALPL SPTA1
3 chronic recurrent multifocal osteomyelitis 9.9
4 osteomyelitis 9.9
5 myopathy 9.9
6 hypochondrogenesis 9.9 ALPL SPTA1
7 tick infestation 9.9 ALPL ALPP
8 seminoma 9.7 ALPG ALPP
9 hypophosphatasia, infantile 9.7 ALPL ALPP SPTA1
10 bone disease 9.7 ALPL ALPP
11 germ cell cancer 9.7 ALPG ALPP
12 testis seminoma 9.6 ALPI ALPL ALPP
13 testicular germ cell tumor 9.6 ALPG ALPP
14 choriocarcinoma 9.6 ALPG ALPP

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



Diseases related to Hypophosphatasia, Childhood

Symptoms & Phenotypes for Hypophosphatasia, Childhood

Human phenotypes related to Hypophosphatasia, Childhood:

33 (show all 17)
# Description HPO Frequency HPO Source Accession
1 frontal bossing 33 HP:0002007
2 seizures 33 HP:0001250
3 carious teeth 33 HP:0000670
4 short stature 33 HP:0004322
5 myopathy 33 HP:0003198
6 dolichocephaly 33 HP:0000268
7 waddling gait 33 HP:0002515
8 proptosis 33 HP:0000520
9 skin dimple over apex of long bone angulation 33 HP:0001024
10 craniosynostosis 33 HP:0001363
11 bowing of the legs 33 HP:0002979
12 premature loss of primary teeth 33 HP:0006323
13 low alkaline phosphatase 33 HP:0003282
14 rachitic rosary 33 HP:0000897
15 phosphoethanolaminuria 33 HP:0003239
16 elevated urine pyrophosphate 33 HP:0003491
17 elevated plasma pyrophosphate 33 HP:0011864

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Face:
frontal bossing

Growth Height:
short stature

Head And Neck Eyes:
proptosis

Laboratory Abnormalities:
low alkaline phosphatase
phosphoethanolaminuria
elevated plasma and urine inorganic pyrophosphate (ppi)

Head And Neck Teeth:
dental caries
premature deciduous tooth loss (less than five years of age)

Skeletal:
rachitic skeletal changes

Neurologic Central Nervous System:
seizures
myopathy

Head And Neck Head:
dolichocephaly
craniostenosis

Skin Nails Hair Skin:
skin dimple over apex of long bone angulation

Chest Ribs Sternum Clavicles And Scapulae:
rachitic rosary

Skeletal Limbs:
bowed legs
characteristic metaphyseal radiolucency

Clinical features from OMIM:

241510

UMLS symptoms related to Hypophosphatasia, Childhood:


seizures, waddling gait

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

27
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased cell migration GR00055-A-1 9.13 ALPG ALPI ALPL
2 Decreased focal adhesion (FA) area, decreased FA length, decreased FA mean intensity, increased number of small and round FAs, increased FA abundance GR00210-A 8.8 ALPI ALPL ALPP

Drugs & Therapeutics for Hypophosphatasia, Childhood

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Hypophosphatasia, Childhood

Genetic Tests for Hypophosphatasia, Childhood

Genetic tests related to Hypophosphatasia, Childhood:

# Genetic test Affiliating Genes
1 Childhood Hypophosphatasia 30 ALPL

Anatomical Context for Hypophosphatasia, Childhood

MalaCards organs/tissues related to Hypophosphatasia, Childhood:

42
Bone, Skin

Publications for Hypophosphatasia, Childhood

Articles related to Hypophosphatasia, Childhood:

(show all 20)
# Title Authors Year
1
Reappearance of hypomineralized bone after discontinuation of asfotase alfa treatment for severe childhood hypophosphatasia. ( 29967930 )
2018
2
Asfotase alfa treatment for 1 year in a 16 year-old male with severe childhood hypophosphatasia. ( 29046930 )
2018
3
Childhood hypophosphatasia: to treat or not to treat. ( 30012160 )
2018
4
Early Tooth Loss in Children: A Warning Sign of Childhood Hypophosphatasia. ( 29172356 )
2017
5
Childhood Hypophosphatasia with Homozygous Mutation of ALPL. ( 25100374 )
2014
6
Infantile loss of teeth: odontohypophosphatasia or childhood hypophosphatasia. ( 23093139 )
2013
7
Childhood hypophosphatasia with myopathy: clinical report with recent update. ( 22781519 )
2012
8
Neurosurgical aspects of childhood hypophosphatasia. ( 18769927 )
2009
9
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. ( 19335222 )
2009
10
Long-term follow-up of bone mineral density in childhood hypophosphatasia. ( 17420150 )
2007
11
Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. ( 16803637 )
2006
12
Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene. ( 15671102 )
2005
13
Childhood hypophosphatasia: a case report due to a novel mutation. ( 15135428 )
2004
14
G317D mutation in the tissue-nonspecific alkaline phosphatase gene associated with childhood hypophosphatasia in a German family. ( 12638946 )
2002
15
Bone metabolism and bone mineral density in childhood hypophosphatasia. ( 10495141 )
1999
16
Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs. ( 10574582 )
1999
17
Childhood hypophosphatasia. A case report. ( 9188264 )
1997
18
Childhood hypophosphatasia with oral manifestations. ( 289724 )
1979
19
Childhood hypophosphatasia and the premature loss of teeth. A clinical and laboratory study of seven cases. ( 4512507 )
1973
20
Childhood hypophosphatasia. Clinical and cytogenetic studies. ( 4506889 )
1972

Variations for Hypophosphatasia, Childhood

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

76
# Symbol AA change Variation ID SNP ID
1 ALPL p.Ala177Thr VAR_006155 rs199669988
2 ALPL p.Arg223Trp VAR_013986 rs766076920
3 ALPL p.Thr68Met VAR_025907
4 ALPL p.Arg71Ser VAR_025908 rs121918001
5 ALPL p.Leu275Pro VAR_025923 rs123725205
6 ALPL p.Arg391His VAR_025934 rs144291812

ClinVar genetic disease variations for Hypophosphatasia, Childhood:

6 (show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh37 Chromosome 1, 21900176: 21900176
2 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh38 Chromosome 1, 21573683: 21573683
3 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
4 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh38 Chromosome 1, 21564139: 21564139
5 ALPL NM_000478.5(ALPL): c.407G> A (p.Arg136His) single nucleotide variant Pathogenic/Likely pathogenic rs121918011 GRCh37 Chromosome 1, 21889712: 21889712
6 ALPL NM_000478.5(ALPL): c.407G> A (p.Arg136His) single nucleotide variant Pathogenic/Likely pathogenic rs121918011 GRCh38 Chromosome 1, 21563219: 21563219
7 ALPL NM_000478.5(ALPL): c.485G> T (p.Gly162Val) single nucleotide variant Uncertain significance rs121918012 GRCh37 Chromosome 1, 21890546: 21890546
8 ALPL NM_000478.5(ALPL): c.485G> T (p.Gly162Val) single nucleotide variant Uncertain significance rs121918012 GRCh38 Chromosome 1, 21564053: 21564053
9 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh37 Chromosome 1, 21889651: 21889651
10 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh38 Chromosome 1, 21563158: 21563158
11 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Conflicting interpretations of pathogenicity rs121918018 GRCh37 Chromosome 1, 21894694: 21894694
12 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Conflicting interpretations of pathogenicity rs121918018 GRCh38 Chromosome 1, 21568201: 21568201
13 ALPL NM_000478.5(ALPL): c.526G> A (p.Ala176Thr) single nucleotide variant Likely pathogenic rs121918019 GRCh37 Chromosome 1, 21890587: 21890587
14 ALPL NM_000478.5(ALPL): c.526G> A (p.Ala176Thr) single nucleotide variant Likely pathogenic rs121918019 GRCh38 Chromosome 1, 21564094: 21564094
15 ALPL NM_000478.5(ALPL): c.814C> T (p.Arg272Cys) single nucleotide variant Pathogenic rs121918020 GRCh37 Chromosome 1, 21896819: 21896819
16 ALPL NM_000478.5(ALPL): c.814C> T (p.Arg272Cys) single nucleotide variant Pathogenic rs121918020 GRCh38 Chromosome 1, 21570326: 21570326
17 ALPL NM_000478.5(ALPL): c.188G> T (p.Gly63Val) single nucleotide variant Uncertain significance rs1490668038 GRCh37 Chromosome 1, 21887596: 21887596
18 ALPL NM_000478.5(ALPL): c.188G> T (p.Gly63Val) single nucleotide variant Uncertain significance rs1490668038 GRCh38 Chromosome 1, 21561103: 21561103

Expression for Hypophosphatasia, Childhood

Search GEO for disease gene expression data for Hypophosphatasia, Childhood.

Pathways for Hypophosphatasia, Childhood

GO Terms for Hypophosphatasia, Childhood

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

# Name GO ID Score Top Affiliating Genes
1 anchored component of membrane GO:0031225 8.92 ALPG ALPI ALPL ALPP

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

# Name GO ID Score Top Affiliating Genes
1 dephosphorylation GO:0016311 8.92 ALPG ALPI ALPL ALPP

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

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.65 ALPG ALPI ALPL ALPP SPTA1
2 hydrolase activity GO:0016787 9.62 ALPG ALPI ALPL ALPP
3 magnesium ion binding GO:0000287 9.37 ALPI ALPP
4 catalytic activity GO:0003824 9.33 ALPI ALPL ALPP
5 phosphatase activity GO:0016791 9.26 ALPG ALPI ALPL ALPP
6 alkaline phosphatase activity GO:0004035 8.92 ALPG ALPI ALPL ALPP

Sources for Hypophosphatasia, Childhood

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
Content
Loading form....