Case series: Odontohypophosphatasia or missed diagnosis of childhood/adult-onset hypophosphatasia? - Call for a long-term follow-up of premature loss of primary teeth.

Introduction: Hypophosphatasia, a metabolic bone disease caused by a tissue-nonspecific alkaline phosphatase deficiency, leads to undermineralization of bone and/or teeth, impaired vitamin B6 metabolism, and a spectrum of disease presentation. At the mild end of the spectrum, it presents as pathologic fractures in later adulthood. Patients with isolated dental manifestations, typically presenting as premature loss of primary teeth, are classified as having odontohypophosphatasia (odontoHPP). A subset of patients diagnosed with odontoHPP in childhood can later develop extra-dental manifestations that constitute childhood- or adult-onset hypophosphatasia.

Case Reports Methods/results: Retrospective data related to onset, detailed clinical course, and method of diagnosis were collected as part of a natural history of adult patients with hypophosphatasia. Of 9 initial patients, all had low serum alkaline phosphatase levels for their age and gender at adult presentation (Table 2). The majority (8/9) demonstrated childhood dental signs of hypophosphatasia as the initial clinical manifestation: premature loss of primary teeth (7/9), absent primary teeth (1/9), and delayed loss of primary teeth (1/9). Despite childhood dental presentation and/or other signs/symptoms, diagnosis of hypophosphatasia was delayed 20-54 years (median = 46) since the primary tooth problems and 8-45 years (median = 27) since the first fracture or onset of a major adult tooth problem.

Conclusion: Patients with primary tooth loss in childhood were often diagnosed with hypophosphatasia later in life. Pediatric patients classified as having odontoHPP under present practice can manifest significant disease burden later in life.