MCID: HYP292
MIFTS: 43

Hypophosphatasia, Infantile

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

Aliases & Classifications for Hypophosphatasia, Infantile

MalaCards integrated aliases for Hypophosphatasia, Infantile:

Name: Hypophosphatasia, Infantile 54 13 52
Infantile Hypophosphatasia 12 56 29 14 69
Perinatal Lethal Phosphoethanolaminuria 56
Hypophosphatasia, Perinatal Lethal 69
Perinatal Lethal Hypophosphatasia 56
Perinatal Lethal Rathburn Disease 56
Infantile Phosphoethanolaminuria 56
Hypophosphatasia Infantile Type 71
Infantile Rathburn Disease 56
Phosphoethanolaminuria 12
Hopsi 71
Hops 12

Characteristics:

Orphanet epidemiological data:

56
perinatal lethal hypophosphatasia
Inheritance: Autosomal recessive; Age of onset: Antenatal,Neonatal;
infantile hypophosphatasia
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
fever of unknown origin
stillborn or infantile death usual in prenatal form
four separate types - (1) severe perinatal ('lethal') form, (2) severe infantile form, (3) childhood form, and (4) adult form
death frequent in severe infantile form
severe infantile form presents before 6 months


HPO:

32
hypophosphatasia, infantile:
Mortality/Aging stillbirth death in infancy
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hypophosphatasia, Infantile

UniProtKB/Swiss-Prot : 71 Hypophosphatasia infantile type: A severe bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Three more or less distinct types of infantile hypophosphatasia can be identified: (1) type 1 with onset in utero or in early postnatal life, craniostenosis, severe skeletal abnormalities, hypercalcemia, and death in the first year or so of life; (2) type 2 with later, more gradual development of symptoms, moderately severe 'rachitic' skeletal changes and premature loss of teeth; (3) type 3 with no symptoms, the condition being determined on routine studies.

MalaCards based summary : Hypophosphatasia, Infantile, also known as infantile hypophosphatasia, is related to hypophosphatasia, adult and thyrotoxic periodic paralysis, and has symptoms including failure to thrive, recurrent respiratory infections and nephrocalcinosis. An important gene associated with Hypophosphatasia, Infantile is ALPL (Alkaline Phosphatase, Liver/Bone/Kidney), and among its related pathways/superpathways are NAD metabolism and Post-translational modification- synthesis of GPI-anchored proteins. The drugs Immunoglobulins and Antibodies have been mentioned in the context of this disorder. 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 : 54
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, infantile, childhood (241510), and adult (146300). Whyte (1988) indicated a fifth form of hypophosphatasia with primarily only dental manifestations, referred to as odontohypophosphatasia (see 146300). All of these forms are allelic. (241500)

Related Diseases for Hypophosphatasia, Infantile

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



Diseases related to Hypophosphatasia, Infantile

Symptoms & Phenotypes for Hypophosphatasia, Infantile

Symptoms via clinical synopsis from OMIM:

54

Growth- Other:
failure to thrive

Respiratory:
recurrent respiratory infections
apnea

Laboratory- Abnormalities:
hypercalciuria
hypercalcemia
phosphoethanolaminuria
elevated plasma and urine inorganic pyrophosphate (ppi)
decreased tissue and serum alkaline phosphatase
more
Prenatal Manifestations- Amniotic Fluid:
polyhydramnios

Chest- Ribs Sternum Clavicles And Scapulae:
short ribs
rachitic rosary
small thoracic cage
rib fractures
clavicles least affected bone

Skeletal:
fractures
lack of ossification
marked retardation of infantile form

Skeletal- Skull:
widened cranial sutures
poorly mineralized cranium
craniosynostosis in infantile form

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

Voice:
high pitched cry

Prenatal Manifestations- Delivery:
stillborn or infantile death usual in prenatal form

Neurologic- Central Nervous System:
hypotonia
seizures
irritability
intracranial hemorrhage

Genitourinary- Kidneys:
nephrocalcinosis

Skeletal- Spine:
platyspondyly
vertebral bodies often unossified
vertebral clefts

Abdomen- Gastroin testinal:
vomiting
constipation
anorexia

Skeletal- Limbs:
micromelia
metaphyseal cupping
osteogenesis defect
bowed, short lower extremities
'spurs' in midshaft of ulna and fibula

Growth- Height:
short limb dwarfism

Head And Neck- Eyes:
blue sclera

Head And Neck- Teeth:
poorly formed teeth

Hematology:
myelophthisic anemia


Clinical features from OMIM:

241500

Human phenotypes related to Hypophosphatasia, Infantile:

32 (show all 37)
id Description HPO Frequency HPO Source Accession
1 failure to thrive 32 HP:0001508
2 recurrent respiratory infections 32 HP:0002205
3 nephrocalcinosis 32 HP:0000121
4 hypercalciuria 32 HP:0002150
5 seizures 32 HP:0001250
6 anemia 32 HP:0001903
7 irritability 32 HP:0000737
8 platyspondyly 32 HP:0000926
9 polyhydramnios 32 HP:0001561
10 vomiting 32 HP:0002013
11 apnea 32 HP:0002104
12 short ribs 32 HP:0000773
13 constipation 32 HP:0002019
14 fever 32 HP:0001945
15 hypercalcemia 32 HP:0003072
16 micromelia 32 HP:0002983
17 craniosynostosis 32 HP:0001363
18 muscular hypotonia 32 HP:0001252
19 blue sclerae 32 HP:0000592
20 metaphyseal cupping 32 HP:0003021
21 increased susceptibility to fractures 32 HP:0002659
22 anorexia 32 HP:0002039
23 intracranial hemorrhage 32 HP:0002170
24 bowing of the legs 32 HP:0002979
25 short lower limbs 32 HP:0006385
26 rachitic rosary 32 HP:0000897
27 unossified vertebral bodies 32 HP:0004606
28 vertebral clefting 32 HP:0008428
29 abnormality of the voice 32 HP:0001608
30 disproportionate short-limb short stature 32 HP:0008873
31 skin dimple over apex of long bone angulation 32 HP:0001024
32 decreased calvarial ossification 32 HP:0005474
33 widely patent fontanelles and sutures 32 HP:0004492
34 abnormality of the dentition 32 HP:0000164
35 phosphoethanolaminuria 32 HP:0003239
36 elevated urine pyrophosphate 32 HP:0003491
37 elevated plasma pyrophosphate 32 HP:0011864

UMLS symptoms related to Hypophosphatasia, Infantile:


constipation, fever of unknown origin, seizures, vomiting

Drugs & Therapeutics for Hypophosphatasia, Infantile

Drugs for Hypophosphatasia, Infantile (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Immunoglobulins Phase 1, Phase 2
2 Antibodies Phase 1, Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP) Completed NCT00744042 Phase 1, Phase 2
2 Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP) Completed NCT01205152 Phase 2
3 Expanded Access Program for Asfotase Alfa Treatment for Patients With Infantile- or Juvenile-onset Hypophosphatasia (HPP) Approved for marketing NCT02496689
4 A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP) Completed NCT01419028
5 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168
6 Health Burden of Hypophosphatasia Not yet recruiting NCT02751801

Search NIH Clinical Center for Hypophosphatasia, Infantile

Genetic Tests for Hypophosphatasia, Infantile

Genetic tests related to Hypophosphatasia, Infantile:

id Genetic test Affiliating Genes
1 Infantile Hypophosphatasia 29

Anatomical Context for Hypophosphatasia, Infantile

MalaCards organs/tissues related to Hypophosphatasia, Infantile:

39
Bone, Skin

Publications for Hypophosphatasia, Infantile

Variations for Hypophosphatasia, Infantile

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

71
id Symbol AA change Variation ID SNP ID
1 ALPL p.Phe327Leu VAR_006165 rs121918010
2 ALPL p.Lys224Glu VAR_011084
3 ALPL p.Gly426Cys VAR_011089
4 ALPL p.Gly456Arg VAR_011091 rs121918016
5 ALPL p.Tyr28Cys VAR_013972
6 ALPL p.Val459Met VAR_013998
7 ALPL p.Glu298Lys VAR_025928 rs121918017

ClinVar genetic disease variations for Hypophosphatasia, Infantile:

6 (show all 47)
id Gene Variation Type Significance SNP ID Assembly Location
1 ALPL NM_000478.5(ALPL): c.535G> A (p.Ala179Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918000 GRCh37 Chromosome 1, 21890596: 21890596
2 ALPL NM_000478.5(ALPL): c.211C> T (p.Arg71Cys) single nucleotide variant Pathogenic rs121918001 GRCh37 Chromosome 1, 21887619: 21887619
3 ALPL NM_000478.5(ALPL): c.881A> C (p.Asp294Ala) single nucleotide variant Pathogenic rs121918002 GRCh37 Chromosome 1, 21900176: 21900176
4 ALPL NM_000478.5(ALPL): c.212G> C (p.Arg71Pro) single nucleotide variant Pathogenic rs121918003 GRCh37 Chromosome 1, 21887620: 21887620
5 ALPL NM_000478.5(ALPL): c.620A> C (p.Gln207Pro) single nucleotide variant Pathogenic rs121918004 GRCh37 Chromosome 1, 21890681: 21890681
6 ALPL NM_000478.5(ALPL): c.98C> T (p.Ala33Val) single nucleotide variant Pathogenic rs121918005 GRCh37 Chromosome 1, 21887155: 21887155
7 ALPL NM_000478.5(ALPL): c.1306T> C (p.Tyr436His) single nucleotide variant Pathogenic rs121918006 GRCh37 Chromosome 1, 21903131: 21903131
8 ALPL NM_000478.5(ALPL): c.892G> A (p.Glu298Lys) single nucleotide variant Pathogenic rs121918017 GRCh37 Chromosome 1, 21900187: 21900187
9 ALPL NM_000478.5(ALPL): c.571G> A (p.Glu191Lys) single nucleotide variant Pathogenic/Likely pathogenic rs121918007 GRCh37 Chromosome 1, 21890632: 21890632
10 ALPL NM_000478.5(ALPL): c.1133A> T (p.Asp378Val) single nucleotide variant Pathogenic rs121918008 GRCh37 Chromosome 1, 21902361: 21902361
11 ALPL NM_000478.5(ALPL): c.1001G> A (p.Gly334Asp) single nucleotide variant Pathogenic/Likely pathogenic rs121918009 GRCh37 Chromosome 1, 21902229: 21902229
12 ALPL NM_000478.5(ALPL): c.979T> C (p.Phe327Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121918010 GRCh37 Chromosome 1, 21900274: 21900274
13 ALPL NM_000478.5(ALPL): c.1559delT (p.Leu520Argfs) deletion Pathogenic rs387906525 GRCh37 Chromosome 1, 21904125: 21904125
14 ALPL NM_000478.5(ALPL): c.407G> A (p.Arg136His) single nucleotide variant Pathogenic/Likely pathogenic rs121918011 GRCh37 Chromosome 1, 21889712: 21889712
15 ALPL NM_000478.5(ALPL): c.346G> A (p.Ala116Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121918013 GRCh37 Chromosome 1, 21889651: 21889651
16 ALPL NM_000478.5(ALPL): c.648+1G> A single nucleotide variant Pathogenic rs749544042 GRCh38 Chromosome 1, 21564217: 21564217
17 ALPL NM_000478.5(ALPL): c.1250A> G (p.Asn417Ser) single nucleotide variant Pathogenic/Likely pathogenic rs121918014 GRCh37 Chromosome 1, 21903075: 21903075
18 ALPL NM_000478.5(ALPL): c.1366G> A (p.Gly456Arg) single nucleotide variant Pathogenic rs121918016 GRCh37 Chromosome 1, 21903932: 21903932
19 ALPL NM_000478.5(ALPL): c.526G> A (p.Ala176Thr) single nucleotide variant Pathogenic rs121918019 GRCh37 Chromosome 1, 21890587: 21890587
20 ALPL NM_000478.5(ALPL): c.814C> T (p.Arg272Cys) single nucleotide variant Pathogenic rs121918020 GRCh37 Chromosome 1, 21896819: 21896819
21 ALPL NM_000478.5(ALPL): c.215T> C (p.Ile72Thr) single nucleotide variant Likely pathogenic rs781264043 GRCh37 Chromosome 1, 21887623: 21887623
22 ALPL NM_000478.5(ALPL): c.400_401delACinsCA (p.Thr134His) indel Pathogenic/Likely pathogenic rs786204530 GRCh38 Chromosome 1, 21563212: 21563213
23 ALPL NM_000478.5(ALPL): c.542C> T (p.Ser181Leu) single nucleotide variant Likely pathogenic rs199590449 GRCh37 Chromosome 1, 21890603: 21890603
24 ALPL NM_000478.5(ALPL): c.667C> T (p.Arg223Trp) single nucleotide variant Likely pathogenic rs766076920 GRCh37 Chromosome 1, 21894615: 21894615
25 ALPL NM_000478.5(ALPL): c.791A> G (p.Lys264Arg) single nucleotide variant Likely pathogenic rs786204442 GRCh38 Chromosome 1, 21568246: 21568246
26 ALPL NM_000478.5(ALPL): c.809G> A (p.Trp270Ter) single nucleotide variant Likely pathogenic rs786204634 GRCh37 Chromosome 1, 21896814: 21896814
27 ALPL NM_000478.5(ALPL): c.871G> A (p.Glu291Lys) single nucleotide variant Likely pathogenic rs786204473 GRCh38 Chromosome 1, 21573673: 21573673
28 ALPL NM_000478.5(ALPL): c.891C> A (p.Tyr297Ter) single nucleotide variant Likely pathogenic rs755529290 GRCh38 Chromosome 1, 21573693: 21573693
29 ALPL NM_000478.5(ALPL): c.46_49delAACT (p.Asn16Profs) deletion Likely pathogenic rs1057516230 GRCh38 Chromosome 1, 21554127: 21554130
30 ALPL NM_000478.5(ALPL): c.61+2T> G single nucleotide variant Likely pathogenic rs764322898 GRCh37 Chromosome 1, 21880637: 21880637
31 ALPL NM_000478.5(ALPL): c.88C> T (p.Arg30Ter) single nucleotide variant Likely pathogenic rs1057516334 GRCh38 Chromosome 1, 21560652: 21560652
32 ALPL NM_000478.5(ALPL): c.114delA (p.Lys38Asnfs) deletion Likely pathogenic rs1057517321 GRCh38 Chromosome 1, 21560678: 21560678
33 ALPL NM_000478.5(ALPL): c.129delT (p.Gln44Argfs) deletion Likely pathogenic rs1057517122 GRCh37 Chromosome 1, 21887186: 21887186
34 ALPL NM_000478.5(ALPL): c.130C> T (p.Gln44Ter) single nucleotide variant Likely pathogenic rs1057516293 GRCh37 Chromosome 1, 21887187: 21887187
35 ALPL NM_000478.5(ALPL): c.297+2T> A single nucleotide variant Likely pathogenic rs1057517304 GRCh37 Chromosome 1, 21887707: 21887707
36 ALPL NM_000478.5(ALPL): c.522delC (p.Ser175Alafs) deletion Likely pathogenic rs1057516978 GRCh37 Chromosome 1, 21890583: 21890583
37 ALPL NM_000478.5(ALPL): c.662dupG (p.Gly222Trpfs) duplication Likely pathogenic rs1057516443 GRCh37 Chromosome 1, 21894610: 21894610
38 ALPL NM_000478.5(ALPL): c.841delC (p.His281Thrfs) deletion Likely pathogenic rs1057516526 GRCh38 Chromosome 1, 21570353: 21570353
39 ALPL NM_000478.5(ALPL): c.903delG (p.Asn302Thrfs) deletion Likely pathogenic rs1057516748 GRCh38 Chromosome 1, 21573705: 21573705
40 ALPL NM_000478.5(ALPL): c.928_929delTC (p.Ser310Argfs) deletion Likely pathogenic rs1057516702 GRCh38 Chromosome 1, 21573730: 21573731
41 ALPL NM_000478.5(ALPL): c.997+2T> G single nucleotide variant Pathogenic rs1057517391 GRCh37 Chromosome 1, 21900294: 21900294
42 ALPL NM_000478.5(ALPL): c.998-2A> G single nucleotide variant Likely pathogenic rs1057516622 GRCh38 Chromosome 1, 21575731: 21575731
43 ALPL NM_000478.5(ALPL): c.1088_1091dupGCAG (p.Ser364Argfs) duplication Likely pathogenic rs1057517322 GRCh37 Chromosome 1, 21902316: 21902319
44 ALPL NM_000478.5(ALPL): c.1144G> A (p.Val382Ile) single nucleotide variant Likely pathogenic rs771540767 GRCh37 Chromosome 1, 21902372: 21902372
45 ALPL NM_000478.5(ALPL): c.1363G> A (p.Gly455Ser) single nucleotide variant Likely pathogenic rs149889416 GRCh37 Chromosome 1, 21903929: 21903929
46 ALPL NM_000478.5(ALPL): c.1426G> T (p.Glu476Ter) single nucleotide variant Likely pathogenic rs1057517173 GRCh37 Chromosome 1, 21903992: 21903992
47 ALPL NM_000478.5(ALPL): c.1530_1549del20 (p.Leu512Profs) deletion Likely pathogenic rs1057517337 GRCh38 Chromosome 1, 21577603: 21577622

Expression for Hypophosphatasia, Infantile

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

Pathways for Hypophosphatasia, Infantile

Pathways related to Hypophosphatasia, Infantile according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.56 ALPL ALPP
2
Show member pathways
11.25 ALPL PIGV
3 10.36 ALPL ALPP
4 10.16 ALPL ALPP
5
Show member pathways
9.66 ALPP PNPO

GO Terms for Hypophosphatasia, Infantile

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

id Name GO ID Score Top Affiliating Genes
1 anchored component of membrane GO:0031225 8.62 ALPL ALPP

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

id Name GO ID Score Top Affiliating Genes
1 dephosphorylation GO:0016311 8.96 ALPL ALPP
2 metabolic process GO:0008152 8.8 ALDH4A1 ALPL ALPP

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

id Name GO ID Score Top Affiliating Genes
1 phosphatase activity GO:0016791 8.96 ALPL ALPP
2 alkaline phosphatase activity GO:0004035 8.62 ALPL ALPP

Sources for Hypophosphatasia, Infantile

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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