Hypophosphatasia (HPP) is an inherited disease caused by mutation of the alkaline phosphatase (ALPL) gene in an autosomal dominant or an autosomal recessive manner. The main symptoms of HPP are bone hypomineralization and early exfoliation of the primary teeth. Some of the mutations identified in autosomal dominant families are reported to have dominant negative effects. In addition, the penetrance can vary among patients with the same variant even within the same family, resulting in various phenotypes of systemic symptoms. However, differences in dental symptoms between patients with HPP and carriers with the same ALPL variant have not been reported. Herein, we report on two sisters who had the same heterozygous ALPL variant with dominant negative effects. The older sister had bone and dental symptoms and was diagnosed with childhood HPP. In contrast, the younger sister was a carrier with no bone and dental symptoms. It can be inferred that this phenomenon was caused by the difference in penetrance. This case revealed that carriers with the ALPL mutation may have no dental symptoms characteristic of HPP. Because HPP is sometimes progressive, it is very important to carefully monitor carriers to detect the possible onset of dental and systemic symptoms.
Keywords: ALPL gene mutation; early exfoliation; hypophosphatasia; inherited disorder.