ORPHA:436
Hypophosphatasia
Synonyms: HPP · Phosphoethanolaminuria · Rathbun disease
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal dominant, Autosomal recessive
- Age of onset
- All ages
- Status
- active
A rare, genetic metabolic disorder characterized by reduced activity of unfractionated serum alkaline phosphatase (ALP) and various symptoms from life-threatening, severely impaired mineralization at birth to musculo-skeletal pain in adulthood.
1
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Hypophosphatasia | HPP · Phosphoethanolaminuria · Rathbun disease |
| fr | Hypophosphatasie | HPP · Maladie de Rathbun · Phosphoéthanolaminurie |
| de | Hypophosphatasie | HPP · Phosphoethanolaminurie · Rathbun-Syndrom |
| es | Hipofosfatasia | Enfermedad de Rathburn · Fosfoetanolaminuria · HPP |
| it | Ipofosfatasia | Fosfoetanolaminuria · HPP · Malattia di Rathburn |
| nl | Hypofosfatasie | Fosfo-ethanolaminurie · HPP · Ziekte van Rathbun |
| pt | Hipofosfatasia | Doença de Rathburn · Fosfoetanolaminúria |
| pl | Hipofosfatazja | Choroba Rathburna · Fosfoetanololaminuria · HPP |
| cs | Hypofosfatázie | HPP · Fosfoetanolaminurie · Rathburnova choroba |
| uk | Гіпофосфатазія | HPP · Фосфоетаноламінурія · Хвороба Ратбуна |
| zh | 低磷酸酯酶症 | 磷酸乙醇胺尿症 |
| tr | Hipofosfatazya | HPP · Rathbun hastalığı · Fosfoetanolaminüri |
Definition in:
2
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 146300 | BTNT | validated | |
| OMIM | 241500 | BTNT | validated | |
| OMIM | 241510 | BTNT | validated | |
| ICD-10 | E83.3 | NTBT | inclusion | validated |
| ICD-11 | 5C64.3 | NTBT | index | validated |
| MONDO | 0018570 | E | validated | |
| MeSH | D007014 | E | validated | |
| UMLS | C0020630 | E | validated | |
| GARD | 6734 | E | validated | |
| MedDRA | 10049933 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
3
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (2):
- ORPHA:139009Developmental anomaly of metabolic origin
rare developmental anomalies during embryogenesis; rare genetic diseases - ORPHA:93447Primary bone dysplasia with defective bone mineralization
rare developmental anomalies during embryogenesis; rare genetic diseases; rare bone diseases
4
Genes
0 direct · 6 via subtypesOrphanet records no gene directly on this code.
Recorded by Orphanet on subtypes of this disorder:
| Gene | Subtype | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|---|
| ALPL | ORPHA:247623Perinatal lethal hypophosphatasia | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:438 | ENSG00000162551 | 171760 | 1p36.12 | alkaline phosphatase, biomineralization associated | 10737975[PMID]_17916236[PMID]_20301329[PMID] |
| ALPL | ORPHA:247638Prenatal benign hypophosphatasia | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:438 | ENSG00000162551 | 171760 | 1p36.12 | alkaline phosphatase, biomineralization associated | 10737975[PMID]_17916236[PMID]_20301329[PMID] |
| ALPL | ORPHA:247651Infantile hypophosphatasia | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:438 | ENSG00000162551 | 171760 | 1p36.12 | alkaline phosphatase, biomineralization associated | 10737975[PMID]_17916236[PMID]_20301329[PMID] |
| ALPL | ORPHA:247667Childhood-onset hypophosphatasia | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:438 | ENSG00000162551 | 171760 | 1p36.12 | alkaline phosphatase, biomineralization associated | 10737975[PMID]_17916236[PMID]_20301329[PMID] |
| ALPL | ORPHA:247676Adult hypophosphatasia | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:438 | ENSG00000162551 | 171760 | 1p36.12 | alkaline phosphatase, biomineralization associated | 10737975[PMID]_17916236[PMID]_20301329[PMID] |
| ALPL | ORPHA:247685Odontohypophosphatasia | Disease-causing germline mutation(s) (loss of function) in | Assessed | HGNC:438 | ENSG00000162551 | 171760 | 1p36.12 | alkaline phosphatase, biomineralization associated | 10737975[PMID]_17916236[PMID]_20301329[PMID] |
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Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Point prevalence | Unknown | — | Worldwide | Class only | Validated | ORPHANET_[EXPERT]_21488855[PMID] |
| Point prevalence | <1 / 1 000 000 | 0.0208 / 100 000 | China | Value and class | Validated | 34103049[PMID] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
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HPO phenotypes
44 annotations · validated 2026-03-16| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0000944 | Abnormal metaphysis morphology | |
| HP:0000772 | Abnormal rib morphology | |
| HP:0000164 | Abnormality of the dentition | |
| HP:0003282 | Decreased circulating alkaline phosphatase activity | |
| HP:0002097 | Emphysema | |
| HP:0008872 | Feeding difficulties in infancy | |
| HP:0000239 | Large fontanelles | |
| HP:0000774 | Narrow chest | |
| Frequent (79-30%) | ||
| HP:0002653 | Bone pain | |
| HP:0000934 | Chondrocalcinosis | |
| HP:0012532 | Chronic pain | |
| HP:0001363 | Craniosynostosis | |
| HP:0032537 | Delayed fracture healing | |
| HP:0032477 | Elevated circulating vitamin B6 concentration | |
| HP:0003491 | Elevated urine pyrophosphate | |
| HP:0001531 | Failure to thrive in infancy | |
| HP:0012378 | Fatigue | |
| HP:0001288 | Gait disturbance | |
| HP:0001510 | Growth delay | |
| HP:0003072 | Hypercalcemia | |
| HP:0001252 | Hypotonia | |
| HP:0002659 | Increased susceptibility to fractures | |
| HP:0041162 | Metatarsal fracture | |
| HP:0001270 | Motor delay | |
| HP:0002756 | Pathologic fracture | |
| HP:0003239 | Phosphoethanolaminuria | |
| HP:0006323 | Premature loss of primary teeth | |
| HP:0100036 | Pseudo-fractures | |
| HP:0002757 | Recurrent fractures | |
| HP:0002748 | Rickets | |
| HP:0001250 | Seizure | |
| HP:0004322 | Short stature | |
| HP:0002360 | Sleep abnormality | |
| Occasional (29-5%) | ||
| HP:0006487 | Bowing of the long bones | |
| HP:0000670 | Carious teeth | |
| HP:0002150 | Hypercalciuria | |
| HP:0002516 | Increased intracranial pressure | |
| HP:0000737 | Irritability | |
| HP:0001324 | Muscle weakness | |
| HP:0000121 | Nephrocalcinosis | |
| HP:0000787 | Nephrolithiasis | |
| HP:0002749 | Osteomalacia | |
| HP:0002093 | Respiratory insufficiency | |
| HP:0010781 | Skin dimple | |
Run the differential on the 8 obligate / very frequent terms
Annotation source: 37982857[PMID]_40047955[PMID]_37249457[PMID]_20301329[PMID]
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Sources for this card
- Orphanet page: orpha.net/en/disease/detail/436
- This record as JSON: /data/d/436.json