Odontohypophosphatasia treated with asfotase alfa enzyme replacement therapy in a toddler: a case report

Abstract

Hypophosphatasia (HPP) is a rare skeletal disorder caused by loss-of-function mutations in Alkaline Phosphatase, Biomineralization associated (ALPL) gene that encodes tissue-nonspecific alkaline phosphatase. Odontohypophosphatasia (odonto-HPP), a mild form of HPP, is characterized only by oral manifestations including premature exfoliation of deciduous teeth. Enzyme replacement therapy (ERT) is effective in severe HPP cases; however, information about its efficacy for odonto-HPP is limited. A 2-yr-old girl was referred to our hospital for mobility of her deciduous teeth with low serum alkaline phosphatase (ALP) level of 253 U/L (reference range: 410–1,150 U/L) and high urine phosphoethanolamine level of 1,419.9 µmol/g·Cre (7–70 µmol/g·Cre). She had no history of bone fractures; however, several members of her family had low serum ALP levels with a history of pathological fractures. She had a novel heterozygous missense mutation (c.1183A>T, p.Ile395Phe) in ALPL, and therefore, was diagnosed with odonto-HPP. After she was provided ERT to prevent premature exfoliation, no tooth mobility was observed. However, two deciduous teeth exfoliated two months after starting ERT, which was possibly triggered by a bout of common cold. Starting ERT following tooth mobility might be relatively late. Previous studies on experimental mice showed that starting ERT at birth may be effective in preventing premature exfoliation of deciduous teeth.