title: Hypophosphatasia: diagnosis and clinical signs - a dental surgeon perspective.
abstract: BACKGROUND
  Hypophosphatasia (HPP) is a rare inherited metabolic disease in which mutations in the ALPL gene (encoding tissue-nonspecific alkaline phosphatase) result in varying degrees of enzyme deficiency. HPP manifests in a spectrum of symptoms, including early primary tooth loss (root intact) and alveolar bone mineralisation defects.
  
  
  OBJECTIVE
  To provide an overview of HPP for dental professionals to help recognise and differentially diagnose patients for appropriate referral to a specialist team.
  
  
  METHODS
  A non-systematic review of publications on HPP was performed.
  
  
  RESULTS
  Different forms of HPP are described, along with characteristic symptoms and laboratory findings. Diagnosis is challenging due to the rareness and variable presentation of symptoms. Low alkaline phosphatase levels are a signature of HPP, but reference ranges vary according to gender and age. Key features are defined and management strategies discussed, focusing on enzyme replacement therapy. Finally, a patient registry aimed at better defining the prevalence of HPP and raising awareness is described.
  
  
  CONCLUSIONS
  HPP is a rare disease with a wide spectrum of manifestations, with orodental symptoms featuring prominently in the natural history. Dental professionals may be positioned at the beginning of the diagnostic pathway; thus, recognition of HPP features for timely referral and optimal disease management is important.
authors.affiliation: Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France. agnes.bloch-zupan@unistra.fr.|Hôpitaux Universitaires de Strasbourg, Pôle de Médecine et Chirurgie Bucco-Dentaires, Centre de référence des manifestations odontologiques des maladies rares (CRMR), Reference Centre for Orodental Manifestations of Rare Diseases, Strasbourg, France. agnes.bloch-zupan@unistra.fr.|Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS-UdS UMR7104, Université de Strasbourg, Illkirch, France. agnes.bloch-zupan@unistra.fr.|Eastman Dental Institute, University College London, London, UK. agnes.bloch-zupan@unistra.fr.
authors.forename: Agnès
authors.initials: A
authors.lastname: Bloch-Zupan
mesh_terms: D002648:Child; D019140:Dental Care for Children; D003937:Diagnosis, Differential; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis*; D012017:Referral and Consultation