MCID: HYP596
MIFTS: 32

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 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

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 hypophosphatasia, infantile, and has symptoms including seizures and waddling gait. An important gene associated with Hypophosphatasia, Childhood is ALPL (Alkaline Phosphatase, Liver/Bone/Kidney). Affiliated tissues include bone and skin, and related phenotypes are dolichocephaly and proptosis

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.

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

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 30.9 ALPL SPTA1
2 hypophosphatasia, infantile 9.3 ALPL SPTA1
3 hypophosphatasia, adult 9.2 ALPL SPTA1

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

UMLS symptoms related to Hypophosphatasia, Childhood:


seizures, waddling gait

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 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 18)
# Title Authors Year
1
Reappearance of hypomineralized bone after discontinuation of asfotase alfa treatment for severe childhood hypophosphatasia. ( 29967930 )
2018
2
Early Tooth Loss in Children: A Warning Sign of Childhood Hypophosphatasia. ( 29172356 )
2017
3
Childhood Hypophosphatasia with Homozygous Mutation of ALPL. ( 25100374 )
2014
4
Infantile loss of teeth: odontohypophosphatasia or childhood hypophosphatasia. ( 23093139 )
2013
5
Childhood hypophosphatasia with myopathy: clinical report with recent update. ( 22781519 )
2012
6
Neurosurgical aspects of childhood hypophosphatasia. ( 18769927 )
2009
7
Chronic recurrent multifocal osteomyelitis mimicked in childhood hypophosphatasia. ( 19335222 )
2009
8
Long-term follow-up of bone mineral density in childhood hypophosphatasia. ( 17420150 )
2007
9
Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. ( 16803637 )
2006
10
Childhood hypophosphatasia due to a de novo missense mutation in the tissue-nonspecific alkaline phosphatase gene. ( 15671102 )
2005
11
Childhood hypophosphatasia: a case report due to a novel mutation. ( 15135428 )
2004
12
G317D mutation in the tissue-nonspecific alkaline phosphatase gene associated with childhood hypophosphatasia in a German family. ( 12638946 )
2002
13
Bone metabolism and bone mineral density in childhood hypophosphatasia. ( 10495141 )
1999
14
Treatment of childhood hypophosphatasia with nonsteroidal antiinflammatory drugs. ( 10574582 )
1999
15
Childhood hypophosphatasia. A case report. ( 9188264 )
1997
16
Childhood hypophosphatasia with oral manifestations. ( 289724 )
1979
17
Childhood hypophosphatasia and the premature loss of teeth. A clinical and laboratory study of seven cases. ( 4512507 )
1973
18
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
6 ALPL p.Arg391His VAR_025934

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 rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
4 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant 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 Pathogenic rs121918012 GRCh37 Chromosome 1, 21890546: 21890546
8 ALPL NM_000478.5(ALPL): c.485G> T (p.Gly162Val) single nucleotide variant Pathogenic 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 Pathogenic rs121918018 GRCh37 Chromosome 1, 21894694: 21894694
12 ALPL NM_000478.5(ALPL): c.746G> T (p.Gly249Val) single nucleotide variant Pathogenic 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 GRCh37 Chromosome 1, 21887596: 21887596
18 ALPL NM_000478.5(ALPL): c.188G> T (p.Gly63Val) single nucleotide variant Uncertain significance 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

Sources for Hypophosphatasia, Childhood

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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33 ICD10
34 ICD10 via Orphanet
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45 MESH via Orphanet
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62 PubMed
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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