HOPSC
MCID: HYP596
MIFTS: 33

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 57 13 55
Childhood Hypophosphatasia 12 53 29 6 15 40 73
Childhood-Onset Phosphoethanolaminuria 53 59
Childhood-Onset Hypophosphatasia 53 59
Childhood-Onset Rathburn Disease 53 59
Hypophosphatasia Childhood Type 75
Hopsc 75

Characteristics:

Orphanet epidemiological data:

59
childhood-onset hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Childhood,Infancy;

OMIM:

57
Miscellaneous:
waddling gait
delayed onset of walking
presentation after 6 months

Inheritance:
autosomal recessive


HPO:

32
hypophosphatasia, childhood:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 241510
Disease Ontology 12 DOID:0110915
Orphanet 59 ORPHA247667
ICD10 via Orphanet 34 E83.3
UMLS via Orphanet 74 C0220743
MedGen 42 C0220743
UMLS 73 C0220743

Summaries for Hypophosphatasia, Childhood

NIH Rare Diseases : 53 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 chronic recurrent multifocal osteomyelitis, and has symptoms including seizures and waddling gait. An important gene associated with Hypophosphatasia, Childhood is ALPL (Alkaline Phosphatase, Biomineralization Associated). 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 : 57 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 : 75 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:

# Related Disease Score Top Affiliating Genes
1 hypophosphatasia 32.4 ALPL SPTA1
2 chronic recurrent multifocal osteomyelitis 9.9
3 osteomyelitis 9.9
4 myopathy 9.9
5 hypophosphatasia, infantile 9.8 ALPL SPTA1
6 hypophosphatasia, adult 9.8 ALPL SPTA1
7 hypochondrogenesis 9.7 ALPL SPTA1

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



Diseases related to Hypophosphatasia, Childhood

Symptoms & Phenotypes for Hypophosphatasia, Childhood

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Hypophosphatasia, Childhood:

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 frontal bossing 32 HP:0002007
2 seizures 32 HP:0001250
3 carious teeth 32 HP:0000670
4 short stature 32 HP:0004322
5 myopathy 32 HP:0003198
6 dolichocephaly 32 HP:0000268
7 waddling gait 32 HP:0002515
8 proptosis 32 HP:0000520
9 skin dimple over apex of long bone angulation 32 HP:0001024
10 craniosynostosis 32 HP:0001363
11 bowing of the legs 32 HP:0002979
12 premature loss of primary teeth 32 HP:0006323
13 low alkaline phosphatase 32 HP:0003282
14 rachitic rosary 32 HP:0000897
15 phosphoethanolaminuria 32 HP:0003239
16 elevated urine pyrophosphate 32 HP:0003491
17 elevated plasma pyrophosphate 32 HP:0011864

UMLS symptoms related to Hypophosphatasia, Childhood:


seizures, waddling gait

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:

41
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:

75
# 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.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
2 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh37 Chromosome 1, 21900176: 21900176
3 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh38 Chromosome 1, 21573683: 21573683
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 GRCh38 Chromosome 1, 21561103: 21561103
18 ALPL NM_000478.5(ALPL): c.188G> T (p.Gly63Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 21887596: 21887596

Expression for Hypophosphatasia, Childhood

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

Pathways for Hypophosphatasia, Childhood

GO Terms for Hypophosphatasia, Childhood

Sources for Hypophosphatasia, Childhood

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10 dbSNP
11 DGIdb
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64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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