Perinatal lethal hypophosphatasia

General Information (adopted from Orphanet):

Synonyms, Signs: HOPS
Perinatal lethal Rathburn disease
Perinatal lethal phosphoethanolaminuria
Phosphoethanolaminuria hypophosphatasia, perinatal lethal, included
Number of Symptoms 78
OrphanetNr: 247623
OMIM Id: 241500
ICD-10: E83.3
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: <= 0.3 - PMID: 30508915 [IBIS]
Inheritance: Autosomal recessive
- PMID: 30508915 [IBIS]
Age of onset: Antenatal
Neonatal
- PMID: 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

Symptom Information: Sort by abundance 

1
 (HPO:0003239) Phosphoethanolaminuria 3174660 IBIS 3 / 7739
2
 (HPO:0010683) Low tissue non-specific alkaline phosphatase 3174660 IBIS 1 / 7739
3
 (HPO:0003811) Neonatal death 30508915 IBIS 44 / 7739
4
 (MedDRA:10058610) Urine calcium/creatinine ratio increased 30508915 IBIS 1 / 7739
5
 (HPO:0002150) Hypercalciuria 30508915 IBIS 45 / 7739
6
 (HPO:0008250) Infantile hypercalcemia 30508915 IBIS 3 / 7739
7
 (HPO:0000772) Abnormality of the ribs 30508915 IBIS 146 / 7739
8
 (HPO:0002089) Pulmonary hypoplasia 30508915 IBIS 80 / 7739
9
 (HPO:0005257) Thoracic hypoplasia 30508915 IBIS 79 / 7739
10
 (HPO:0000034) Hydrocele testis 30508915 IBIS 18 / 7739
11
 (HPO:0030148) Heart murmur 30508915 IBIS 29 / 7739
12
 (HPO:0001388) Joint laxity 30508915 IBIS 117 / 7739
13
 (HPO:0008947) Infantile muscular hypotonia 30508915 IBIS 482 / 7739
14
 (HPO:0001252) Muscular hypotonia 30508915 IBIS 990 / 7739
15
 (HPO:0000470) Short neck 30508915 IBIS 345 / 7739
16
 (HPO:0003865) Bowed humerus 30508915 IBIS 5 / 7739
17
 (HPO:0005792) Short humerus 30508915 IBIS 34 / 7739
18
 (HPO:0006385) Short lower limbs 30508915 IBIS 8 / 7739
19
 (HPO:0002979) Bowing of the legs 30508915 IBIS 28 / 7739
20
 (HPO:0001290) Generalized hypotonia 30508915 IBIS 51 / 7739
21
 (HPO:0002093) Respiratory insufficiency 30508915 IBIS 410 / 7739
22
 (HPO:0004349) Reduced bone mineral density 3174660; 30508915 IBIS 165 / 7739
23
 (HPO:0003026) Short long bone 30508915 IBIS 51 / 7739
24
 (HPO:0003282) Low alkaline phosphatase 24276437; 30508915 IBIS 7 / 7739
25
 (HPO:0000774) Narrow chest 24276437 IBIS 167 / 7739
26
 (HPO:0003015) Flared metaphysis 24276437 IBIS 44 / 7739
27
 (HPO:0011314) Abnormality of long bone morphology 24276437 IBIS 3 / 7739
28
 (HPO:0000365) Hearing impairment 24276437 IBIS 539 / 7739
29
 (HPO:0001363) Craniosynostosis 24276437 IBIS 132 / 7739
30
 (HPO:0001249) Intellectual disability 24276437 IBIS 1089 / 7739
31
 (HPO:0006323) Premature loss of primary teeth 24276437 IBIS 18 / 7739
32
 (HPO:0001531) Failure to thrive in infancy 24276437 IBIS 26 / 7739
33
 (HPO:0004322) Short stature 24276437 IBIS 1232 / 7739
34
 (HPO:0000260) Wide anterior fontanel 24276437 IBIS 55 / 7739
35
 (HPO:0001250) Seizures 24276437 IBIS 1245 / 7739
36
 (HPO:0002878) Respiratory failure 24276437 IBIS 57 / 7739
37
 (HPO:0002757) Recurrent fractures 24276437 IBIS 47 / 7739
38
 (HPO:0009826) Limb undergrowth 25731960; 24276437 IBIS 8 / 7739
39
 (HPO:0001522) Death in infancy 25731960; 3174660 IBIS 275 / 7739
40
 (HPO:0002098) Respiratory distress 25731960 IBIS 75 / 7739
41
 (HPO:0000765) Abnormality of the thorax 25731960 IBIS 64 / 7739
42
 (HPO:0000239) Large fontanelles 25731960; 30508915 IBIS 135 / 7739
43
 (HPO:0005474) Decreased calvarial ossification 25731960; 30508915 IBIS 8 / 7739
44
 (HPO:0003826) Stillbirth 40 / 7739
45
 (HPO:0003491) Elevated urine pyrophosphate 2 / 7739
46
 (HPO:0000121) Nephrocalcinosis 57 / 7739
47
 (HPO:0000164) Abnormality of the teeth 291 / 7739
48
 (HPO:0004331) Decreased skull ossification 31 / 7739
49
 (MedDRA:10039117) Rib fracture 2 / 7739
50
 (HPO:0010537) Wide cranial sutures 21 / 7739
51
 (HPO:0004492) Widely patent fontanelles and sutures 11 / 7739
52
 (HPO:0000592) Blue sclerae 85 / 7739
53
 (HPO:0000737) Irritability 93 / 7739
54
 (HPO:0000773) Short ribs 70 / 7739
55
 (HPO:0002983) Micromelia 130 / 7739
56
 (HPO:0000897) Rachitic rosary 5 / 7739
57
 (HPO:0003021) Metaphyseal cupping 16 / 7739
58
 (HPO:0004606) Unossified vertebral bodies 4 / 7739
59
 (HPO:0008428) Vertebral clefting 4 / 7739
60
 (HPO:0000926) Platyspondyly 150 / 7739
61
 (HPO:0002659) Increased susceptibility to fractures 110 / 7739
62
 (HPO:0001561) Polyhydramnios 191 / 7739
63
 (HPO:0002019) Constipation 194 / 7739
64
 (HPO:0002013) Vomiting 191 / 7739
65
 (HPO:0002039) Anorexia 62 / 7739
66
 (HPO:0008873) Disproportionate short-limb short stature 39 / 7739
67
 (HPO:0001508) Failure to thrive 454 / 7739
68
 (HPO:0001024) Skin dimple over apex of long bone angulation 3 / 7739
69
 (HPO:0002170) Intracranial hemorrhage 40 / 7739
70
 (HPO:0001903) Anemia 289 / 7739
71
 (HPO:0011864) Elevated plasma pyrophosphate 2 / 7739
72
 (HPO:0001945) Fever 218 / 7739
73
 (HPO:0003072) Hypercalcemia 36 / 7739
74
 (HPO:0001608) Abnormality of the voice 126 / 7739
75
 (HPO:0002104) Apnea 106 / 7739
76
 (HPO:0002205) Recurrent respiratory infections 254 / 7739
77
 (HPO:0001324) Muscle weakness 859 / 7739
78
 (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 ...