title: Hypophosphatasia.
abstract: 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.
authors.affiliation: Department of Pediatric Endocrinology and Diabetology for Children, APHP, Bicêtre Paris Sud, Le Kremlin Bicêtre, 94270, France. agnes.linglart@aphp.fr.|APHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism and Plateforme d'Expertise Paris Sud Maladies Rares, Le Kremlin Bicêtre, 94270, France. agnes.linglart@aphp.fr.
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.affiliation: APHP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism and Plateforme d'Expertise Paris Sud Maladies Rares, Le Kremlin Bicêtre, 94270, France.|Department of Odontology, APHP, Bretonneau Paris Nord Val de Seine, Paris, 75018, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Biosse-Duplan
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000627:therapeutic use*; D002136:Calcium, Dietary; D003729:Dental Care; D019468:Disease Management; D056947:Enzyme Replacement Therapy; D005598:Fractures, Spontaneous / Q000209:etiology; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D007014:Hypophosphatasia / Q000150:complications / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D007074:Immunoglobulin G / Q000627:therapeutic use*; D009154:Mutation; D018529:Nutritional Support; D066087:Perinatal Death / Q000209:etiology; D016226:Phosphorus, Dietary; D026741:Physical Therapy Modalities; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D012640:Seizures / Q000209:etiology; D014080:Tooth Exfoliation / Q000209:etiology; D014808:Vitamin D Deficiency / Q000175:diagnosis / Q000209:etiology
chemical_list: D002136:Calcium, Dietary; D007074:Immunoglobulin G; D016226:Phosphorus, Dietary; D011993:Recombinant Fusion Proteins; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; C570710:asfotase alfa
keywords: Alkaline phosphatase; Asfotase alfa; Craniosynostosis; Exfoliated teeth; Hypophosphatasia; Rickets