Abstract
Hypophosphatasia (HPP) is a rare and intractable metabolic bone disease caused by mutations in the ALPL gene. Here, we undertook a nationwide survey of HPP in Japan, specifically regarding the prominent genetic and dental manifestations of odonto (n = 16 cases) and other (termed “non-odonto”) (n = 36 cases) types. Mean serum alkaline phosphatase (ALP) values in odonto-type patients were significantly greater than those of non-odonto-type patients (P<0.05). Autosomal dominant and autosomal recessive inheritance patterns were detected, respectively, in 89% of odonto-type and 96% of non-odonto-type patients. The ALPL “c.1559delT” mutation, associated with extremely low ALP activity, was found in approximately 70% of cases. Regarding dental manifestations, all patients classified as odonto-type showed early exfoliation of the primary teeth significantly more frequently than patients classified as non-odonto-type (100% vs. 56%; P<0.05). Tooth hypomineralisation was detected in 42% of non-odonto-type patients, but not in any odonto-type patients (0%; P<0.05). Collectively, these results suggest that genetic and dental manifestations of patients with odonto-type and non-odonto-type HPP are significantly different, and these differences should be considered during clinical treatment of patients with HPP.
Highlights
Hypophosphatasia (HPP) is a rare, metabolic bone disease caused by mutation of the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (ALP) in bone osteoblasts, and liver, kidney, and skin fibroblasts
Patients diagnosed with severe-type HPP generally die before the emergence of primary teeth in the oral cavity
The use of Enzyme replacement therapy (ERT) was introduced in Japan, which drastically improved the prognosis of patients with HPP, including those with severe-type HPP [19,20,21,22,23,24,25], and increased the opportunities for these patients to Genetic and dental findings in hypophosphatasia receive dental management later, when necessary [26,27]
Summary
Hypophosphatasia (HPP) is a rare, metabolic bone disease caused by mutation of the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (ALP) in bone osteoblasts, and liver, kidney, and skin fibroblasts. HPP is classified into six subtypes depending on the time of diagnosis and symptoms: perinatal severe (in utero and at birth), perinatal benign, infantile (before 6 months of age), childhood (after 6 months of age to 18 years old), adult (after 18 years old) and odonto (at all ages after tooth eruption, with only dental symptoms) [1,3,4,5,6]. Symptoms are typically more severe with earlier-aged diagnoses, except for perinatal-benign and odonto types [1,3,4,5,6]. In less-severe types, such as odonto or childhood types, dental signs are often the first clues toward a diagnosis [7,11,12]
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