Disease name and synonyms
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Hypophosphatasia
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Phosphoethanolaminuria
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Rathbun disease
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HOPS
Definition and diagnostic criteria
Epidemiology
Clinical description
Clinical form | Inheritance | Bone symptoms | Dental symptoms | Clinical diagnosis |
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Perinatal lethal | AR | Hypomineralization Osteochondral spurs | na | Radiographs Ultrasonography |
Prenatal benign | AD | Bowing of long bones Benign post-natal | na | Ultrasonography Clinical examination |
Infantile | AR | Craniosynostosis Hypomineralization Rachitic ribs Hypercalciuria | Premature loss of deciduous teeth | Clinical examination Biology (serum AP activity, PEA and PLP). Radiographs |
Childhood | AR (frequent) or AD (rare) | Short stature Skeletal deformity Waddling gait Bone pain/fractures | Premature loss of deciduous teeth | |
Adult | AR or AD | Stress fractures: metatarsal, tibia Osteoarthritis | +/- | |
Odontohypophosphatasia | AR or AD | Loss of alveolar bone | Exfoliation (incisors). Reduced thickness of the dentin. Enlarged pulp chambers of teeth. Dental caries | Clinical examination. Biology (serum AP activity, PEA and PLP). |
Etiology
Genotype-Phenotype correlations
Class | Cell localization | Degradation, other features | 3D model localization | Mutation and reference | AP activity (% wild type) |
---|---|---|---|---|---|
1 | Intracellular accumulation; fails to move beyond the cis-Golgi | Degradation in the proteasome | Functional domains (homodimer interface, calcium binding site, active site) | R54C (c.211C>T), [29] | 0 |
N153D (c.508A>G) [32] | 0 | ||||
I201T (c.653T>C) [40] | 0 | ||||
E218G (c.704A>G) [19]; [26] | 0 | ||||
D277A (c.881A>C) [29] | 0 | ||||
D289V (c.917A>T) [33] | 0 | ||||
G317D (c.1001G>A) [25] | 0 | ||||
2 | Intracellular accumulation; fails to move beyond the cis-Golgi | Degradation in the proteasome | Not localized in a particular domain | A162T (c.535G>A) [26]; [29] | 18 |
G232V (c.746G>T) [40] | 34 | ||||
3 | Cell membrane and cytoplasme | Not localized in a particular domain | F310L c.979T>C [28] | 72 | |
E174K (c.571G>A) [40] | 88 | ||||
I473F (c.1468A>T) [40] | 37 | ||||
Active site vicinity | G438S (c.1363G>A) [40] | 71 | |||
4 | Cell membrane | Not localized in a particular domain | A115V (c.395C>T) [34] | 17 | |
Intracellular localization; absence on cell surface | Large-sized secretory protein lacking GPI; aggregation due to disulphide bonds beween new cystein residues | c.1559delT [35] | 28 | ||
Cell membrane | Disulphide bond between new cystein residues | Crown domain | R433C (c.1348C>T) [39] | 4 |
The dominant effect of TNAP mutations
Diagnostic methods
Laboratory assays
Molecular biology
Differential diagnosis
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Osteogenesis imperfecta
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Rickets
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Achondrogenesis