Hypophosphatasia is a rare disorder due to a mutation in the ALPL gene encoding the alkaline phosphatase (ALP) leading to a diminished activity of the enzyme in bone, liver, and kidney. Hypophosphatasia is a heterogeneous disease, ranging from extreme life-threatening forms revealed at birth in young infants presenting with severely impaired bone mineralization, seizures, and hypercalcemia, to young adults with premature exfoliation of their teeth without any other symptom. We will review the challenges of the clinical, biochemical, radiological, and genetic diagnosis. Schematically, the diagnosis relies on low ALP levels and, in most cases, on the genetic defect in the ALPL gene. An enzyme replacement therapy is now developed for hypophosphatasia; early results in the severe form of the disease are extremely encouraging. However, multidisciplinary care remains the core of treatment of hypophosphatasia encompassing nutritional support, adjustment of calcium and phosphate intake, monitoring of vitamin D levels, careful and personalized physical therapy, and regular dental monitoring and care.
Keywords: Alkaline phosphatase; Asfotase alfa; Craniosynostosis; Exfoliated teeth; Hypophosphatasia; Rickets.