Hypophosphatasia: diagnosis and clinical signs – a dental surgeon perspective

Abstract

Summary 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.

Dental manifestations of hypophosphatasia in children and the effects of enzyme replacement therapy on dental status: A series of clinical cases

“…Four patients were observed to have various degrees of enamel hypoplasia of the permanent teeth. Similar amelogenesis impairment of the permanent teeth in patients with HPP has also been described by Bloch‐Zupan A …”

Oral Symptoms and Bone Observations in Odonto-Hypophosphatasia

“…Our patient was referred to a physician, and diagnosis was made based on low serum ALP levels and the radiographic dental findings. Numerous studies on dental characterization of HPP have been reported [5] [6], while few reports briefly described the dental management [7] [8]. We observed this patient from the stage of primary dentition to the mixed dentition period.…”

Epilepsy as a Pyridoxine-Dependent Condition: Quantitative Urinary Biomarkers of Epilepsy. Family Disorders of Pyridoxine Metabolism

“…We believe that disorders of pyridoxine metabolism in epileptic families are the consequences of inborn hypophosphatasia caused by a low activity of TNSALP. Mutations in ALPL gene, which encodes TNSALP, are responsible for the reduction of enzymatic activity [71][72][73]. The clinical spectrum of congenital hypophosphatasia presents a wide variety of phenotypesfrom newborn, or infant convulsions controlled by pyridoxine [74][75][76][77][78][79] to their asymptomatic parents [80][81][82][83][84], whose ALP deficiency may be manifested, for example, by osteoarthropathy and/or odontohypophosphatasia.…”