Biochemical and genetic analysis in patients with odontohypophosphatasia in Japan

Takuo Kubota; Yasuhisa Ohata; Yasuki Ishihara; Makoto Fujiwara; Shinji Takeyari; Kenichi Yamamoto; Yukako Nakano; Kei Miyata; Hirofumi Nakayama; Taichi Kitaoka; Rena Okawa; Kazuhiko Nakano; Tomoyuki Akiyama; Keiichi Ozono

doi:10.1530/boneabs.7.P61

Background: Hypophosphatasia (HPP) is characterized by defective mineralization of bone and/or teeth in the presence of low serum alkaline phosphatase (ALP) activity and caused by mutations in the ALPL gene encoding tissue-nonspecific ALP. Odontohypophosphatasia (odonto HPP) is the mildest form of hypophosphatasia and characterized by dental complications without abnormalities of the skeleton system.

Objectives: We aimed to investigate biochemical and genetic features in patients with odonto HPP in Japan.

Methods: We analyzed 9 unrelated Japanese patients with odonto HPP who have visited to our hospital since 2008.

Results: The first primary tooth loss occurred at the age of 2.5 (1.3–4.0) years (median [min.–max.]). Seven patients were referred to our hospital from the department of pediatric dentistry, the nearest dental university hospital and two from the department of pediatrics, other hospitals. Height SDS and weight SDS at the first visit was 0.0 (−2.57 to +1.51) and 0.78 (−1.20 to +1.77), respectively. Serum ALP activities were decreased, 266 (192–361) U/L (The normal range at the age of 2 years is 410 to 1250 [male] or 1150 [female] U/L). Urinary phosphoethanolamine (PEA) levels were elevated, 604 (166–899) nmol/mgCr. In 4 patients, serum levels of pyridoxal 5’-phosphate (PLP) and pyridoxal (PL) were measured. PLP levels were high, 321.9 (132.6–647.2) nmol/L. PL levels were 32.7 (13.7–46.2) nmol/L. PLP/PL ratio was high, 10.2 (6.3–11.7). Ages at the first primary tooth loss were not associated with values of biochemical parameters. Serum ALP activities were negatively correlated with urinary PEA and serum PLP levels. Urinary PEA levels were positively correlated with PLP/PL ratio. Six patients had a heterozygous mutation in the ALPL gene; while only one patient had compound heterozygous mutations.

Discussions: Our study in Japan showed that odonto HPP, the mildest form of HPP, has the biochemical characteristics of HPP and that serum ALP activity is negatively correlated its substrate levels. Genetic analysis indicated the majority of odonto HPP is autosomal dominant form. Further studies, especially comparative analysis of odonto HPP with childhood HPP with premature teeth loss, will be needed to elucidate features of odonto HPP.

Disclosure: Alexion Pharmaceuticals.

Bone Abstracts

P61