Inheritance
Perinatal and infantile hypophosphatasia are inherited as autosomal recessive traits with homozygosity or compound heterozygosity for two defective TNSALP alleles. The mode of inheritance for childhood, adult, and odonto forms of hypophosphatasia can be either autosomal dominant or recessive. Autosomal transmission accounts for the fact that the disease affects males and females with equal frequency. Genetic counseling is complicated by the disease’s variable inheritance pattern31 ; the existence of the rare prenatal benign form, and by incomplete penetration of the trait32.
31 Simon-Bouy B., Taillandier A., Fauvert D., BrunHeath I., Jean-Louis S., Armengod C.G., Bialer M.G., Mathieu M., Cousin J., Chitayat D., Liebelt J., Feldman B., Gerard-Blanluet M., Kortge-Jing S., King C., Laivuori H., Le Merrer M, Mehta S., Jern C., Sharif S., Prieur F., Gillessen-Kaesbach G., Zandl A., Mornet E. (2008) Hypophosphatasia: Molecular testing of 19 prenatal cases and discussion about genetic counseling. Prenat Diagn, 28;993-998.
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32 Mornet E., Lia-Baldini A.S., Brun-Heath I., Taillandier A., Fauvert D., Simon-Bouy B., Serre J.L. (2008). Attempt to estimate the frequency of mild forms of hypophosphatasia. data on file.
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Autosomal Dominant
Autosomal Recessive
Prevalence
HPP is a rare disease that has been reported worldwide and appears to affect individuals of all ethnicities33.
The prevalence of severe hypophosphatasia is estimated to be 1:100,000 in a population of largely Anglo Saxon origin34. The frequency of mild HPP is more challenging to assess because the symptoms may escape notice, or be misdiagnosed. The highest incidence of HPP has been reported in the Mennonite population in Manitoba, Canada where one in every 25 individuals are considered carriers and one in every 2,500 newborns manifests severe disease35.
HPP is considered particularly rare in people of African ancestry in the U.S.36.
33 Whyte M.P., Essmyer K., Geimer M., Mumm S. (2006) Homozygosity for TNSALP mutation 1348C>T (Arg433Cys) causes infantile hypophosphatasia manifesting transient disease correction and variably lethal outcome in a kindred of black ancestry. J Pediatr, 148:753-758.
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34 Fraser D.(1957) Hypophosphatasia. Am J Med 22:730-46.
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35 Greenberg C.R., Taylor C.L.D., Haworth J.C., Seargeant L.E., Phillips S., Triggs-Raine B., Chodirker B.N. (1993). A homoallelic Gly317 β Asp mutation in ALPL causes the perinatal (lethal) form of hypophosphatasia in Canadian Mennonites. Genomics, 17;215-217.
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36 Whyte M.P., Essmyer K., Geimer M., Mumm S. (2006) Homozygosity for TNSALP mutation 1348C>T (Arg433Cys) causes infantile hypophosphatasia manifesting transient disease correction and variably lethal outcome in a kindred of black ancestry. J Pediatr, 148:753-758.
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