Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Hypophosphatasia

Hypophosphatasia is a group of diseases caused by mutations of the ALPL gene. Inheritance is autosomal dominant and recessive. Various forms may be distinguished by the age of clinical manifestation from infancy to adulthood. The clinical picture resembles vitamin D resistent rickets. Laboratory findings include hypercalcemia and ethanolamine phosphatemia.

Laboratory tests

General work-up

Parameter Interpretation
Serum calcium elevated
Serum phosphate elevated
Serum alkaline phosphatase low

Disease-specific work-up

Parameter Interpretation
Serum ethanolamine phosphate elevated
Urinary excretion ethanolamine phosphate elevated

Management

For therapy Strensiq® (asfotase alfa) is available.

Systematic

Hereditary Rickets
Hypophosphatasia
Adult hypophosphatasia
ALPL
Childhood hypophosphatasia
ALPL
Infantile hypophosphatasia
ALPL
Odontohypophosphatasia
ALPL
Hypophosphatemic bone and kindney disease
Vitamin D hydroxylation-deficient rickets type 1A
Vitamin D hydroxylation-deficient rickets type 1B
Vitamin D-dependent rickets, type 2A
Vitamin D-dependent rickets, type 2B

References:

1.

Macfarlane JD et. al. (1992) Phenotypically dissimilar hypophosphatasia in two sibships.

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2.

Henthorn PS et. al. (1992) Different missense mutations at the tissue-nonspecific alkaline phosphatase gene locus in autosomal recessively inherited forms of mild and severe hypophosphatasia.

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3.

Greenberg CR et. al. (1993) A homoallelic Gly317-->Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian mennonites.

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4.

Moore CA et. al. (1999) Mild autosomal dominant hypophosphatasia: in utero presentation in two families.

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5.

Hu JC et. al. (2000) Characterization of a family with dominant hypophosphatasia.

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6.

Lia-Baldini AS et. al. (2001) A molecular approach to dominance in hypophosphatasia.

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7.

Litmanovitz et. al. (2002) Glu274Lys/Gly309Arg mutation of the tissue-nonspecific alkaline phosphatase gene in neonatal hypophosphatasia associated with convulsions.

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8.

Herasse M et. al. (2003) Molecular study of three cases of odontohypophosphatasia resulting from heterozygosity for mutations in the tissue non-specific alkaline phosphatase gene.

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9.

Whyte MP et. al. (2007) Adult hypophosphatasia treated with teriparatide.

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10.

Stevenson DA et. al. (2008) Autosomal recessive hypophosphatasia manifesting in utero with long bone deformity but showing spontaneous postnatal improvement.

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11.

Whyte MP et. al. (1979) Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature.

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12.

Whyte MP et. al. (1978) Adult hypophosphatasia dominant inheritance in a large kindred.

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13.

Whyte MP et. al. (1985) Markedly increased circulating pyridoxal-5'-phosphate levels in hypophosphatasia. Alkaline phosphatase acts in vitamin B6 metabolism.

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14.

Danovitch SH et. al. (1968) Intestinal alkaline phosphatase activity in familial hypophosphatasia.

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15.

Jardon OM et. al. (1970) Hypophosphatasia in an adult.

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16.

Eade AW et. al. (1981) Pyrophosphate arthropathy in hypophosphatasia.

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17.

Fallon MD et. al. (1984) Hypophosphatasia: clinicopathologic comparison of the infantile, childhood, and adult forms.

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18.

Whyte MP et. al. (1982) Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred.

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19.

Whyte MP et. al. (1982) Adult hypophosphatasia: generalized deficiency of alkaline phosphatase activity demonstrated with cultured skin fibroblasts.

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20.

Weinstein RS et. al. (1981) Heterogeneity of adult hypophosphatasia. Report of severe and mild cases.

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21.

Pauli RM et. al. (1999) Mild hypophosphatasia mimicking severe osteogenesis imperfecta in utero: bent but not broken.

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22.

Morava E et. al. (2002) Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia.

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23.

Unger S et. al. (2002) Severe cleidocranial dysplasia can mimic hypophosphatasia.

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24.

None (1957) Hypophosphatasia.

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25.

Scriver CR et. al. (1969) Pseudohypophosphatasia.

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26.

None () Hypophosphatasia associated with calcium pyrophosphate dihydrate deposits in cartilage. Report of a case.

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27.

Méhes K et. al. (1972) Hypophosphatasia: screening and family investigations in an endogamous Hungarian village.

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28.

Warshaw JB et. al. (1971) Serum alkaline phosphatase in hypophosphatasia.

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29.

Whyte MP et. al. (1984) Enzyme replacement therapy for infantile hypophosphatasia attempted by intravenous infusions of alkaline phosphatase-rich Paget plasma: results in three additional patients.

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30.

Eastman JR et. al. (1983) Clinical, laboratory, and genetic investigations of hypophosphatasia: support for autosomal dominant inheritance with homozygous lethality.

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31.

Albeggiani A et. al. (1982) Infantile hypophosphatasia diagnosed at 4 months and surviving at 2 years.

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32.

Wolff C et. al. (1982) Hypophosphatasia congenita letalis.

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33.

Whyte MP et. al. (1982) Infantile hypophosphatasia: enzyme replacement therapy by intravenous infusion of alkaline phosphatase-rich plasma from patients with Paget bone disease.

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34.

Eastman J et. al. (1982) Lethal and mild hypophosphatasia in half-sibs.

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35.

Kousseff BG et. al. (1981) Prenatal diagnosis of hypophosphatasia.

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36.

Vandevijver N et. al. (1998) Lethal hypophosphatasia, spur type: case report and fetopathological study.

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37.

BETHUNE JE et. al. (1960) Hypophosphatasia in the adult.

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38.

RATHBUN JC et. al. (1961) Hypophosphatasia: a genetic study.

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39.

Cahill RA et. al. (2007) Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts.

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40.

None (1948) Hypophosphatasia; a new developmental anomaly.

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41.

Zankl A et. al. (2008) Specific ultrasonographic features of perinatal lethal hypophosphatasia.

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42.

Whyte MP et. al. (2012) Enzyme-replacement therapy in life-threatening hypophosphatasia.

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Update: Sept. 26, 2018