Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jan;19(1):7-13.
doi: 10.1297/cpe.19.7. Epub 2010 Mar 11.

Clinical characteristics of perinatal lethal hypophosphatasia: a report of 6 cases

Akari Nakamura-Utsunomiya  1 , Satoshi Okada, Keiichi Hara, Shinichiro Miyagawa, Kanae Takeda, Rie Fukuhara, Yusei Nakata, Michiko Hayashidani, Kanako Tachikawa, Toshimi Michigami, Keiichi Ozono, Masao Kobayashi
Affiliations

Clinical characteristics of perinatal lethal hypophosphatasia: a report of 6 cases

Akari Nakamura-Utsunomiya et al. Clin Pediatr Endocrinol. 2010 Jan.

Abstract

Hypophosphatasia is a rare inherited disorder caused by deficient tissue-nonspecific alkaline phosphatase activity. It is classified into 6 subtypes, and the perinatal lethal form of hypophosphatasia is the most severe. Patients with this form suffer from various symptoms, including respiratory failure, premature craniosynostosis, rachitic changes in the metaphyses, convulsions and hypercalcemia. This report presents 6 cases of the perinatal lethal form of hypophosphatasia. All of the patients showed shortening of the long bones in utero in ultrasonographic examinations. Two of the six patients died at birth because they could not establish spontaneous breathing. Three of the remaining four patients also died before 1 yr of age. The major cause of death was respiratory failure due to hypoplastic lung. All of the patients, except for the two who died at birth, experienced convulsions in their clinical courses. Vitamin B6 therapy effectively reduced the frequency and severity of convulsions. However, it could not always make the patients convulsion free. Three patients underwent a genetic analysis. The 1559delT mutation, which abolishes Alkaline Phosphatase (ALP) activity, was a hot spot. A homozygous 1559delT mutation was observed in two patients. However, they differed in severity of symptoms. Although a good genotype-phenotype correlation has been reported in hypophosphatasia, the genotype alone does not always predict the life span of the patients. These cases therefore suggested the importance of genetic counseling.

Keywords: ALP; ALPL; Hypophosphatasia; alkaline phosphatase; perinatal lethal form.

PubMed Disclaimer

References

    1. Michigami T, Uchihashi T, Suzuki A, Tachikawa K, Nakajima S, Ozono K. Common mutations F310L and T1559del in the tissue-nonspecific alkaline phosphatase gene are related to distinct phenotypes in Japanese patients with hypophosphatasia. Eur J Pediatr 2005;164: 277–82 - PubMed
    1. Mornet E. Hypophosphatasia. Orphanet J Rare Dis 2007;2: 40 - PMC - PubMed
    1. Moore CA, Curry CJ, Henthorn PS, Smith JA, Smith JC, O’Lague P, et al. Mild autosomal dominant hypophosphatasia: in utero presentation in two families. Am J Med Genet 1999;86: 410–5 - PubMed
    1. Pauli RM, Modaff P, Sipes SL, Whyte MP. Mild hypophosphatasia mimicking severe osteogenesis imperfecta in utero: bent but not broken. Am J Med Genet 1999;86: 434–8 - PubMed
    1. Shohat M, Rimoin DL, Gruber HE, Lachman RS. Perinatal lethal hypophosphatasia: clinical, radiologic and morphologic findings. Pediatr Radiol 1991;21: 421–7 - PubMed