Infantile hypophosphatasia

General Information (adopted from Orphanet):

Synonyms, Signs: HOPS
Infantile phosphoethanolaminuria
Infantile Rathburn disease
Phosphoethanolaminuria hypophosphatasia, perinatal lethal, included
Number of Symptoms 45
OrphanetNr: 247651
OMIM Id: 241500
ICD-10: E83.3
UMLs: C0268412
MeSH:
MedDRA:
Snomed: 55236002

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
25731960 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Hypophosphatasia
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -Rare bone disease
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Rare disease with odontological manifestation
 -Rare odontologic disease

Comment:

This family report indicates that mapping ALPL mutations within the gene does not necessarily help to predict the clinical severity of the phenotype (PMID:24569605).

Symptom Information: Sort by abundance 

1
 (HPO:0002089) Pulmonary hypoplasia 24569605 IBIS 80 / 7739
2
 (HPO:0002703) Abnormality of skull ossification 24569605 IBIS 1 / 7739
3
 (HPO:0003282) Low alkaline phosphatase 24569605 IBIS 7 / 7739
4
 (HPO:0002516) Increased intracranial pressure 24569605 IBIS 47 / 7739
5
 (HPO:0002789) Tachypnea 24569605 IBIS 48 / 7739
6
 (HPO:0000765) Abnormality of the thorax 24569605 IBIS 64 / 7739
7
 (HPO:0002421) Poor head control 24569605 IBIS 23 / 7739
8
 (HPO:0001270) Motor delay 24569605 IBIS 322 / 7739
9
 (HPO:0001252) Muscular hypotonia 24569605 IBIS 990 / 7739
10
 (HPO:0002013) Vomiting 24569605 IBIS 191 / 7739
11
 (HPO:0002015) Dysphagia 24569605 IBIS 301 / 7739
12
 (HPO:0001324) Muscle weakness 25731960 IBIS 859 / 7739
13
 (HPO:0006323) Premature loss of primary teeth 19232125; 25731960 IBIS 18 / 7739
14
 (HPO:0001363) Craniosynostosis 18769927; 25731960; 24569605 IBIS 132 / 7739
15
 (HPO:0001522) Death in infancy 25731960 IBIS 275 / 7739
16
 (HPO:0001250) Seizures 25731960 IBIS 1245 / 7739
17
 (HPO:0000787) Nephrolithiasis 25731960 IBIS 78 / 7739
18
 (HPO:0000121) Nephrocalcinosis 25731960; 24569605 IBIS 57 / 7739
19
 (HPO:0002150) Hypercalciuria 25731960 IBIS 45 / 7739
20
 (HPO:0003072) Hypercalcemia 25731960 IBIS 36 / 7739
21
 (HPO:0002748) Rickets 25731960 IBIS 41 / 7739
22
 (HPO:0000239) Large fontanelles 25731960 IBIS 135 / 7739
23
 (HPO:0008947) Infantile muscular hypotonia 25731960 IBIS 482 / 7739
24
 (HPO:0001508) Failure to thrive 25731960; 24569605 IBIS 454 / 7739
25
 (HPO:0008872) Feeding difficulties in infancy 25731960 IBIS 153 / 7739
26
 (HPO:0003239) Phosphoethanolaminuria 3 / 7739
27
 (HPO:0004331) Decreased skull ossification 31 / 7739
28
 (HPO:0010537) Wide cranial sutures 21 / 7739
29
 (HPO:0000592) Blue sclerae 85 / 7739
30
 (HPO:0000737) Irritability 93 / 7739
31
 (HPO:0000926) Platyspondyly 150 / 7739
32
 (HPO:0000773) Short ribs 70 / 7739
33
 (HPO:0008428) Vertebral clefting 4 / 7739
34
 (HPO:0000897) Rachitic rosary 5 / 7739
35
 (HPO:0003021) Metaphyseal cupping 16 / 7739
36
 (HPO:0002983) Micromelia 130 / 7739
37
 (HPO:0001561) Polyhydramnios 191 / 7739
38
 (HPO:0002019) Constipation 194 / 7739
39
 (HPO:0002039) Anorexia 62 / 7739
40
 (HPO:0008873) Disproportionate short-limb short stature 39 / 7739
41
 (HPO:0001024) Skin dimple over apex of long bone angulation 3 / 7739
42
 (HPO:0002170) Intracranial hemorrhage 40 / 7739
43
 (HPO:0002104) Apnea 106 / 7739
44
 (HPO:0002205) Recurrent respiratory infections 254 / 7739
45
 (HPO:0010547) Muscle flaccidity 466 / 7739

Associated genes:

ALPL;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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, ...
Diagnosis OMIM Chodirker et al. (1990) emphasized the usefulness of elevated serum phosphate level for carrier detection, in addition to serum alkaline phosphatase activity and urinary phosphoethanolamine excretion.

- Prenatal Diagnosis

Greenberg et al. (1988) used RFLP ...
Clinical Description OMIM Hypophosphatasia was first described by Rathbun (1948) in a 9-week-old male infant. In most cases, recessively inherited hypophosphatasia is a grave disorder, fatal in infancy. However, Bethune and Dent (1960) described 2 sisters in their 40s with skeletal trouble ...
Molecular genetics OMIM In a male infant with hypophosphatasia who was born of second-cousin parents and died at 3 months of age, Weiss et al. (1988) identified homozygosity for a mutation in the ALPL gene (A162T; 171760.0001). Functional studies demonstrated that the ...