Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Hypophosphatasie

Die Hypophosphatasie ist eine Gruppe von Erkrankungen, deren Ursache eine Mutation im ALPL-Gen ist. Die Vererbung kann autosomal dominant oder rezessive sein. Entsprechend der klinischen Manifestation vom Kleinkinds- bis Erwachsenenalter werden verschiedene Formen unterschieden. Das klinische Bild ähnelt einer Vitamin D-resistenten Rachitis. Laborchemisch fällt eine Hypercalciämie und ein erhöhter Phosphoethanolaminspiegel im Serum und Urin auf.

Labortest

Allgemeine Laboruntersuchungen

ParameterInterpretation
Serum-Calciumerhöht
Serum-Phosphaterhöht
Serum-Alkalische-Phosphataseerniedrigt

Krankheitsspezifische Laboruntersuchungen

ParameterInterpretation
Serum-Phosphoethanolaminerhöht
Urinausscheidung von Phosphoethanolaminerhöht

Management

Zur Therapie steht das Strensiq® (asfotase alfa) zur Verfügung.

Gliederung

Hereditäre Rachitis
Hypophosphatasie
Adulte Hypophosphatasie
ALPL
Infantile Hypophosphatasie
ALPL
Kindliche Hypophosphatasie
ALPL
Odontohypophosphatasie
ALPL
Hypophosphatämische Knochen- und Nierenerkrankung
Vitamin D-abhängige Rachitis Typ 2A
Vitamin D-abhängige Rachitis Typ 2B
Vitamin D-hydroxylasemangelbedingte Rachitis Typ 1A
Vitamin D-hydroxylasemangelbedingte Rachitis Typ 1B

Referenzen:

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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