MCID: HYP596
MIFTS: 31

Hypophosphatasia, Childhood

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

Aliases & Classifications for Hypophosphatasia, Childhood

MalaCards integrated aliases for Hypophosphatasia, Childhood:

Name: Hypophosphatasia, Childhood 53 13 51
Childhood Hypophosphatasia 12 49 28 14 69
Childhood-Onset Phosphoethanolaminuria 49 55
Childhood-Onset Hypophosphatasia 49 55
Childhood-Onset Rathburn Disease 49 55
Hypophosphatasia Childhood Type 71
Hopsc 71

Characteristics:

Orphanet epidemiological data:

55
childhood-onset hypophosphatasia
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Childhood,Infancy;

OMIM:

53
Miscellaneous:
waddling gait
delayed onset of walking
presentation after 6 months

Inheritance:
autosomal recessive


HPO:

31
hypophosphatasia, childhood:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 241510
Disease Ontology 12 DOID:0110915
Orphanet 55 ORPHA247667
UMLS via Orphanet 70 C0220743
ICD10 via Orphanet 33 E83.3
MedGen 39 C0220743

Summaries for Hypophosphatasia, Childhood

NIH Rare Diseases : 49 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 childhood hypophosphatasia, is related to hypophosphatasia and hypophosphatasia, infantile, and has symptoms including seizures, waddling gait and frontal bossing. An important gene associated with Hypophosphatasia, Childhood is ALPL (Alkaline Phosphatase, Liver/Bone/Kidney). Affiliated tissues include bone and skin.

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

OMIM : 53 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 : 71 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 31.5 ALPL SPTA1
2 hypophosphatasia, infantile 9.6 ALPL SPTA1
3 hypophosphatasia, adult 9.5 ALPL SPTA1

Symptoms & Phenotypes for Hypophosphatasia, Childhood

Symptoms via clinical synopsis from OMIM:

53
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 RibsSternum Clavicles And Scapulae:
rachitic rosary

Skeletal Limbs:
bowed legs
characteristic metaphyseal radiolucency


Clinical features from OMIM:

241510

Human phenotypes related to Hypophosphatasia, Childhood:

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

UMLS symptoms related to Hypophosphatasia, Childhood:


waddling gait, seizures

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 28 ALPL

Anatomical Context for Hypophosphatasia, Childhood

MalaCards organs/tissues related to Hypophosphatasia, Childhood:

38
Bone, Skin

Publications for Hypophosphatasia, Childhood

Articles related to Hypophosphatasia, Childhood:

(show all 17)
# Title Authors Year
1
Early Tooth Loss in Children: A Warning Sign of Childhood Hypophosphatasia. ( 29172356 )
2017
2
Childhood Hypophosphatasia with Homozygous Mutation of ALPL. ( 25100374 )
2014
3
Infantile loss of teeth: odontohypophosphatasia or childhood hypophosphatasia. ( 23093139 )
2013
4
Childhood hypophosphatasia with myopathy: clinical report with recent update. ( 22781519 )
2012
5
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. ( 19335222 )
2009
6
Neurosurgical aspects of childhood hypophosphatasia. ( 18769927 )
2009
7
Long-term follow-up of bone mineral density in childhood hypophosphatasia. ( 17420150 )
2007
8
Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. ( 16803637 )
2006
9
Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene. ( 15671102 )
2005
10
Childhood hypophosphatasia: a case report due to a novel mutation. ( 15135428 )
2004
11
G317D mutation in the tissue-nonspecific alkaline phosphatase gene associated with childhood hypophosphatasia in a German family. ( 12638946 )
2002
12
Bone metabolism and bone mineral density in childhood hypophosphatasia. ( 10495141 )
1999
13
Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs. ( 10574582 )
1999
14
Childhood hypophosphatasia. A case report. ( 9188264 )
1997
15
Childhood hypophosphatasia with oral manifestations. ( 289724 )
1979
16
Childhood hypophosphatasia and the premature loss of teeth. A clinical and laboratory study of seven cases. ( 4512507 )
1973
17
Childhood hypophosphatasia. Clinical and cytogenetic studies. ( 4506889 )
1972

Variations for Hypophosphatasia, Childhood

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

71
# 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
6 ALPL p.Arg391His VAR_025934

ClinVar genetic disease variations for Hypophosphatasia, Childhood:

6
# 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.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
3 ALPL NM_000478.5(ALPL): c.407G> A (p.Arg136His) single nucleotide variant Pathogenic/Likely pathogenic rs121918011 GRCh37 Chromosome 1, 21889712: 21889712
4 ALPL NM_000478.5(ALPL): c.485G> T (p.Gly162Val) single nucleotide variant Pathogenic rs121918012 GRCh37 Chromosome 1, 21890546: 21890546
5 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh37 Chromosome 1, 21889651: 21889651
6 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Pathogenic rs121918018 GRCh37 Chromosome 1, 21894694: 21894694
7 ALPL NM_000478.5(ALPL): c.526G> A (p.Ala176Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918019 GRCh37 Chromosome 1, 21890587: 21890587
8 ALPL NM_000478.5(ALPL): c.814C> T (p.Arg272Cys) single nucleotide variant Pathogenic rs121918020 GRCh37 Chromosome 1, 21896819: 21896819

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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