HPPC
MCID: HYP596
MIFTS: 47

Hypophosphatasia, Childhood (HPPC)

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 57 13 54 39
Childhood Hypophosphatasia 12 20 29 6 15 70
Childhood-Onset Phosphoethanolaminuria 20 58
Childhood-Onset Hypophosphatasia 20 58
Childhood-Onset Rathbun Disease 20 58
Hypophosphatasia Childhood Type 72
Hopsc 72
Hppc 57

Characteristics:

Orphanet epidemiological data:

58
childhood-onset hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Childhood,Infancy;

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
waddling gait
delayed onset of walking
presentation after 6 months

Inheritance:
autosomal recessive


HPO:

31
hypophosphatasia, childhood:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis
Rare odontological diseases


External Ids:

Disease Ontology 12 DOID:0110915
OMIM® 57 241510
ICD10 via Orphanet 33 E83.3
UMLS via Orphanet 71 C0220743
Orphanet 58 ORPHA247667
MedGen 41 C0220743
UMLS 70 C0220743

Summaries for Hypophosphatasia, Childhood

GARD : 20 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, infantile, 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 NAD metabolism and Endochondral Ossification. Affiliated tissues include bone, colon and kidney, and related phenotypes are frontal bossing and carious teeth

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

OMIM® : 57 Hypophosphatasia (HPP) 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) (Updated 20-May-2021)

UniProtKB/Swiss-Prot : 72 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 top 50) (show all 69)
# Related Disease Score Top Affiliating Genes
1 hypophosphatasia 31.5 PTH PHOSPHO1 ENPP1 ALPL
2 hypophosphatasia, infantile 30.5 PHOSPHO1 ENPP1 ALPL
3 osteomalacia 30.0 PTH ENPP1 ALPL
4 rickets 29.8 PTH IBSP ENPP1 ALPL
5 hypophosphatasia, adult 29.6 PTH PHOSPHO1 ENPP1 ALPL
6 bone disease 29.5 PTH IBSP COL1A1 ALPL
7 bursitis 10.3 PHOSPHO1 ALPL
8 hypercementosis 10.2 PHOSPHO1 ENPP1
9 calcification of joints and arteries 10.2 ENPP1 ALPL
10 pediatric ovarian germ cell tumor 10.1 PTH ENO2
11 bednar tumor 10.1 ENO2 COL1A1
12 pediatric ovarian dysgerminoma 10.1 PTH ENO2
13 periarthritis 10.1 PHOSPHO1 ENPP1 ALPL
14 optic papillitis 10.1 MRAP ACE
15 chlorhexidine allergy 10.1 ENPP3 ACE
16 glossopharyngeal nerve disease 10.1 SLC20A2 ACE
17 dental abscess 10.1 PTH ENPP1
18 iritis 10.1 MRAP ACE
19 enthesopathy 10.0 PTH ENPP1
20 iridocyclitis 10.0 MRAP ACE
21 osteogenesis imperfecta, type vi 10.0 IBSP COL1A1
22 acute mountain sickness 10.0 ENO2 ACE
23 craniometaphyseal dysplasia, autosomal dominant 10.0 IBSP ENPP1 ALPL
24 spondylosis 10.0 PTH ENO2
25 muscular dystrophy, duchenne type 10.0
26 focal segmental glomerulosclerosis 10.0
27 muscular dystrophy 10.0
28 bone benign neoplasm 10.0 PTH ENO2
29 drug allergy 10.0 ENPP3 ACE
30 pseudoxanthoma elasticum 10.0 IBSP ENPP1 ALPL
31 hypophosphatemic rickets, autosomal dominant 10.0 PTH ENPP1
32 hypophosphatemia 10.0 PTH ENPP1 ALPL
33 hypophosphatemic rickets with hypercalciuria, hereditary 10.0 SLC20A2 PTH ENPP1
34 tooth resorption 10.0 PTH IBSP
35 phosphorus metabolism disease 10.0 SLC20A2 PTH ENPP1
36 basal ganglia disease 10.0 SLC20A2 PTH
37 patella, chondromalacia of 10.0 IBSP ACE
38 diffuse scleroderma 9.9 COL1A1 ACE
39 cleidocranial dysplasia 9.9 IBSP COL1A1 ALPL
40 paget's disease of bone 9.9 PTH IBSP ALPL
41 pectus excavatum 9.9
42 chronic recurrent multifocal osteomyelitis 9.9
43 scoliosis 9.9
44 osteomyelitis 9.9
45 craniosynostosis 9.9
46 myopathy 9.9
47 intracranial hypertension 9.9
48 autosomal recessive hypophosphatemic rickets 9.9 PTH IBSP ENPP1
49 ankylosis 9.9 SLC20A2 PHOSPHO1 IBSP ENPP1
50 colon sarcoma 9.9 IBSP ANXA8

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:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 frontal bossing 31 HP:0002007
2 carious teeth 31 HP:0000670
3 short stature 31 HP:0004322
4 myopathy 31 HP:0003198
5 waddling gait 31 HP:0002515
6 dolichocephaly 31 HP:0000268
7 proptosis 31 HP:0000520
8 skin dimple over apex of long bone angulation 31 HP:0001024
9 craniosynostosis 31 HP:0001363
10 premature loss of primary teeth 31 HP:0006323
11 bowing of the legs 31 HP:0002979
12 low alkaline phosphatase 31 HP:0003282
13 rachitic rosary 31 HP:0000897
14 seizure 31 HP:0001250
15 phosphoethanolaminuria 31 HP:0003239
16 elevated urine pyrophosphate 31 HP:0003491
17 elevated plasma pyrophosphate 31 HP:0011864

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
seizures
myopathy

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

Head And Neck Face:
frontal bossing

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 (Updated 20-May-2021)

UMLS symptoms related to Hypophosphatasia, Childhood:


seizures; waddling gait

MGI Mouse Phenotypes related to Hypophosphatasia, Childhood:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.1 ACE ALPL COL1A1 ENO2 ENPP1 ENPP2
2 craniofacial MP:0005382 9.97 ALPL COL1A1 ENO2 ENPP1 IBSP IRF6
3 immune system MP:0005387 9.91 ACE ALPL COL1A1 ENPP1 ENPP2 ENPP3
4 limbs/digits/tail MP:0005371 9.7 ALPL COL1A1 ENPP1 IBSP IRF6 PHOSPHO1
5 mortality/aging MP:0010768 9.7 ACE ALPL COL1A1 ENPP1 ENPP2 ENPP3
6 skeleton MP:0005390 9.23 ALPL COL1A1 ENPP1 IBSP IRF6 PHOSPHO1

Drugs & Therapeutics for Hypophosphatasia, Childhood

Search Clinical Trials , NIH Clinical Center for Hypophosphatasia, Childhood

Genetic Tests for Hypophosphatasia, Childhood

Genetic tests related to Hypophosphatasia, Childhood:

# Genetic test Affiliating Genes
1 Childhood Hypophosphatasia 29 ALPL

Anatomical Context for Hypophosphatasia, Childhood

MalaCards organs/tissues related to Hypophosphatasia, Childhood:

40
Bone, Colon, Kidney

Publications for Hypophosphatasia, Childhood

Articles related to Hypophosphatasia, Childhood:

(show all 42)
# Title Authors PMID Year
1
A molecular approach to dominance in hypophosphatasia. 57 6
11479741 2001
2
Characterization of a family with dominant hypophosphatasia. 6 57
10872988 2000
3
Correlations of genotype and phenotype in hypophosphatasia. 6 57
10332035 1999
4
Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia. 6 57
1409720 1992
5
Unexpected high intrafamilial phenotypic variability observed in hypophosphatasia. 6
24569605 2014
6
Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia. 6
20739387 2010
7
Mild forms of hypophosphatasia mostly result from dominant negative effect of severe alleles or from compound heterozygosity for severe and moderate alleles. 6
19500388 2009
8
Autosomal recessive hypophosphatasia manifesting in utero with long bone deformity but showing spontaneous postnatal improvement. 6
18559907 2008
9
A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb the cell localization of the wild-type protein. 6
18340466 2008
10
Delayed transport of tissue-nonspecific alkaline phosphatase with missense mutations causing hypophosphatasia. 6
17719863 2007
11
Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene. 6
12920074 2003
12
Evidence of a founder effect for the tissue-nonspecific alkaline phosphatase (TNSALP) gene E174K mutation in hypophosphatasia patients. 6
12357339 2002
13
Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia. Mutations in brief no. 217. Online. 6
10094560 1999
14
Aberrant properties of alkaline phosphatase in patient fibroblasts correlate with clinical expressivity in severe forms of hypophosphatasia. 6
8675582 1996
15
Hypophosphatasia. 57
13410963 1957
16
Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene. 54 61
15671102 2005
17
G317D mutation in the tissue-nonspecific alkaline phosphatase gene associated with childhood hypophosphatasia in a German family. 61 54
12638946 2002
18
Bone metabolism and bone mineral density in childhood hypophosphatasia. 54 61
10495141 1999
19
Identification of fifteen novel mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in European patients with severe hypophosphatasia. 61 54
9781036 1998
20
Reappearance of hypomineralized bone after discontinuation of asfotase alfa treatment for severe childhood hypophosphatasia. 61
29967930 2018
21
Childhood hypophosphatasia: to treat or not to treat. 61
30012160 2018
22
[Hypophosphatasia: Clinical manifestations, diagnostic recommendations and therapeutic options]. 61
28720214 2018
23
Asfotase alfa treatment for 1 year in a 16 year-old male with severe childhood hypophosphatasia. 61
29046930 2018
24
Early Tooth Loss in Children: A Warning Sign of Childhood Hypophosphatasia. 61
29172356 2017
25
Childhood hypophosphatasia with homozygous mutation of ALPL. 61
25100374 2014
26
Infantile loss of teeth: odontohypophosphatasia or childhood hypophosphatasia. 61
23093139 2013
27
Childhood hypophosphatasia with myopathy: clinical report with recent update. 61
22781519 2012
28
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. 61
19335222 2009
29
Neurosurgical aspects of childhood hypophosphatasia. 61
18769927 2009
30
Long-term follow-up of bone mineral density in childhood hypophosphatasia. 61
17420150 2007
31
Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. 61
16803637 2006
32
[Hypophosphatasia: report of two affected girls with spontaneous improvement of skeletal defects]. 61
16583935 2005
33
[Childhood hypophosphatasia: a case report due to a novel mutation]. 61
15135428 2004
34
Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs. 61
10574582 1999
35
Molecular diagnosis of hypophosphatasia with severe periodontitis. 61
10397525 1999
36
[Childhood hypophosphatasia]. 61
9380189 1997
37
Childhood hypophosphatasia. A case report. 61
9188264 1997
38
Inheritance of hypophosphatasia. 61
4069031 1985
39
Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms. 61
6690884 1984
40
Childhood hypophosphatasia with oral manifestations. 61
289724 1979
41
Childhood hypophosphatasia and the premature loss of teeth. A clinical and laboratory study of seven cases. 61
4512507 1973
42
Childhood hypophosphatasia. Clinical and cytogenetic studies. 61
4506889 1972

Variations for Hypophosphatasia, Childhood

ClinVar genetic disease variations for Hypophosphatasia, Childhood:

6 (show all 18)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ALPL NM_000478.6(ALPL):c.485G>T (p.Gly162Val) SNV Pathogenic 13676 rs121918012 GRCh37: 1:21890546-21890546
GRCh38: 1:21564053-21564053
2 ALPL NM_000478.6(ALPL):c.746G>T (p.Gly249Val) SNV Pathogenic 13682 rs121918018 GRCh37: 1:21894694-21894694
GRCh38: 1:21568201-21568201
3 ALPL NM_000478.6(ALPL):c.526G>A (p.Ala176Thr) SNV Pathogenic 13683 rs121918019 GRCh37: 1:21890587-21890587
GRCh38: 1:21564094-21564094
4 ALPL NM_000478.6(ALPL):c.814C>T (p.Arg272Cys) SNV Pathogenic 13684 rs121918020 GRCh37: 1:21896819-21896819
GRCh38: 1:21570326-21570326
5 ALPL NM_000478.6(ALPL):c.400_401delinsCA (p.Thr134His) Indel Pathogenic 188877 rs786204530 GRCh37: 1:21889705-21889706
GRCh38: 1:21563212-21563213
6 ALPL NM_000478.6(ALPL):c.1471G>A (p.Gly491Arg) SNV Pathogenic 551446 rs1413274209 GRCh37: 1:21904037-21904037
GRCh38: 1:21577544-21577544
7 ALPL NM_000478.6(ALPL):c.1182dup (p.Ile395fs) Duplication Pathogenic 632629 rs754826836 GRCh37: 1:21902409-21902410
GRCh38: 1:21575916-21575917
8 ALPL NM_000478.6(ALPL):c.881A>C (p.Asp294Ala) SNV Pathogenic 13664 rs121918002 GRCh37: 1:21900176-21900176
GRCh38: 1:21573683-21573683
9 ALPL NM_000478.6(ALPL):c.571G>A (p.Glu191Lys) SNV Pathogenic 13670 rs121918007 GRCh37: 1:21890632-21890632
GRCh38: 1:21564139-21564139
10 ALPL NM_000478.6(ALPL):c.407G>A (p.Arg136His) SNV Pathogenic 13675 rs121918011 GRCh37: 1:21889712-21889712
GRCh38: 1:21563219-21563219
11 ALPL NM_000478.6(ALPL):c.346G>A (p.Ala116Thr) SNV Pathogenic 13677 rs121918013 GRCh37: 1:21889651-21889651
GRCh38: 1:21563158-21563158
12 ALPL NM_000478.6(ALPL):c.571G>A (p.Glu191Lys) SNV Pathogenic 13670 rs121918007 GRCh37: 1:21890632-21890632
GRCh38: 1:21564139-21564139
13 ALPL NM_000478.6(ALPL):c.1001G>A (p.Gly334Asp) SNV Pathogenic 13672 rs121918009 GRCh37: 1:21902229-21902229
GRCh38: 1:21575736-21575736
14 ALPL NM_000478.6(ALPL):c.1133A>T (p.Asp378Val) SNV Pathogenic 13671 rs121918008 GRCh37: 1:21902361-21902361
GRCh38: 1:21575868-21575868
15 ALPL NM_000478.6(ALPL):c.1328C>T (p.Ala443Val) SNV Likely pathogenic 1030812 GRCh37: 1:21903894-21903894
GRCh38: 1:21577401-21577401
16 ALPL NM_000478.6(ALPL):c.526G>A (p.Ala176Thr) SNV Likely pathogenic 13683 rs121918019 GRCh37: 1:21890587-21890587
GRCh38: 1:21564094-21564094
17 ALPL NM_000478.6(ALPL):c.1171C>T (p.Arg391Cys) SNV Likely pathogenic 550442 rs371243939 GRCh37: 1:21902399-21902399
GRCh38: 1:21575906-21575906
18 ALPL NM_000478.6(ALPL):c.98C>T (p.Ala33Val) SNV Uncertain significance 13667 rs121918005 GRCh37: 1:21887155-21887155
GRCh38: 1:21560662-21560662

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

72
# 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

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 extracellular region GO:0005576 9.76 PTH IBSP ENPP3 ENPP2 ENPP1 COL1A1
2 extracellular space GO:0005615 9.56 PTH IBSP ENPP2 ENPP1 ENO2 COL1A1
3 extracellular membrane-bounded organelle GO:0065010 8.62 PHOSPHO1 ALPL

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 skeletal system development GO:0001501 9.63 PTH COL1A1 ALPL
2 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.58 ENPP3 ENPP2 ENPP1
3 osteoblast differentiation GO:0001649 9.5 IBSP COL1A1 ALPL
4 ATP metabolic process GO:0046034 9.49 ENPP3 ENPP1
5 regulation of bone mineralization GO:0030500 9.48 PHOSPHO1 ENPP1
6 phosphate-containing compound metabolic process GO:0006796 9.43 ENPP3 ENPP1
7 response to vitamin D GO:0033280 9.37 PTH ALPL
8 nucleoside triphosphate catabolic process GO:0009143 9.26 ENPP3 ENPP1
9 inorganic diphosphate transport GO:0030505 9.16 ENPP3 ENPP1
10 biomineral tissue development GO:0031214 9.13 IBSP ENPP1 ALPL
11 endochondral ossification GO:0001958 8.8 PHOSPHO1 COL1A1 ALPL

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 10.09 PHOSPHO1 ENPP3 ENPP2 ENPP1 ENO2 COL1A1
2 hydrolase activity GO:0016787 9.93 PHOSPHO1 ENPP3 ENPP2 ENPP1 ALPL ACE
3 catalytic activity GO:0003824 9.78 ENPP3 ENPP2 ENPP1 ALPL
4 polysaccharide binding GO:0030247 9.4 ENPP2 ENPP1
5 NADH pyrophosphatase activity GO:0035529 9.37 ENPP3 ENPP1
6 pyrophosphatase activity GO:0016462 9.32 PHOSPHO1 ALPL
7 nucleoside-triphosphate diphosphatase activity GO:0047429 9.26 ENPP3 ENPP1
8 dTTP diphosphatase activity GO:0036218 9.16 ENPP3 ENPP1
9 nucleotide diphosphatase activity GO:0004551 9.13 ENPP3 ENPP2 ENPP1
10 phosphodiesterase I activity GO:0004528 8.8 ENPP3 ENPP2 ENPP1

Sources for Hypophosphatasia, Childhood

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
Content
Loading form....