title: Neurological Symptoms of Hypophosphatasia.
abstract: Hypophosphatasia (HPP) is a bone metabolic disorder caused by mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL), which encodes tissue-nonspecific alkaline phosphatase (TNAP). This disease is characterized by disrupted bone and tooth mineralization, and reduced serum AP activity. Along with bone and tooth symptoms, many neurological symptoms, seizure, encephalopathy, intracranial hypertension, mental retardation, deafness, and growth hormone deficiency (GHD), are frequently found in HPP patients. Seizure occurs in severe HPP types soon after birth, and responds to pyridoxine, but is an indicator of lethal prognosis. Encephalopathy rarely presents in severe HPP types, but has severe sequelae. Intracranial hypertension complicated in mild HPP types develops after the age of 1 year and sometimes need neurosurgical intervention. Mental retardation, deafness and GHD are more frequently found in Japanese HPP patients. Mental retardation occurs in all HPP types. Deafness in perinatal lethal type is both conductive and sensorineural. GHD develops in all but perinatal lethal type and the diagnosis tends to delay. The pathogenesis of these neural features of HPP might be due to impairment of both vitamin B6 metabolism and central nervous system development by ALPL mutations.
authors.affiliation: Department of Pediatrics, Shimane University Faculty of Medicine, 89-1, Enya, Izumo, Shimane, 693-8501, Japan, ttaketani@med.shimane-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001927:Brain Diseases / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007014:Hypophosphatasia / Q000150:complications* / Q000473:pathology / Q000523:psychology; D019586:Intracranial Hypertension / Q000209:etiology / Q000473:pathology; D009154:Mutation; D012640:Seizures / Q000209:etiology / Q000473:pathology
chemical_list: C548267:ALPL protein, human; D000469:Alkaline Phosphatase