title: Clinical and genetic aspects of hypophosphatasia in Japanese patients.
abstract: OBJECTIVE
  We examined the clinical and genetic features of hypophosphatasia (HPP) in Japanese patients. HPP is a rare metabolic bone disorder of bone mineralisation caused by mutations in the liver/bone/kidney alkaline phosphatase (ALPL) gene, which encodes tissue-non-specific alkaline phosphatase isoenzyme.
  
  
  METHODS
  We retrospectively investigate the incidence and clinical features of 52 patients with paediatric HPP who were born between 1999 and 2010. Mutations of the ALPL gene were analysed in 31 patients.
  
  
  RESULTS
  The annual incidence of perinatal lethal HPP (PLH) was estimated to be 2-3/1 000 000 births. The most frequent clinical type was PLH followed by prenatal benign. In addition to bone symptoms, cerebral manifestations were frequently observed including convulsion, mental retardation, deafness and short stature with growth hormone deficiency. Respiratory failure was the most significant predictor of a poor prognosis for PLH. The first and second most frequent mutations in the ALPL gene were c.1559delT and c.T979C (p.F327L), respectively. The c.1559delT homozygous mutation was lethal with respiratory failure. Patients with the p.F327L compound heterozygous mutation had the different non-lethal type with short stature and a gradual improvement in ALP level and bone mineralisation.
  
  
  CONCLUSIONS
  The most frequent clinical type was the PLH type with prognosis related to respiratory failure, biochemical/radiological changes and ALPL mutations. Cerebral manifestations frequently occurred. Genotype-phenotype correlations were associated with specific outcomes in the PLH type, whereas different clinical features were associated with the same genotype in the non-lethal type.
authors.affiliation: Division of Blood Transfusion, Shimane University Hospital, , Shimane, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Taketani
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Onigata
authors.forename: Hironori
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Mushimoto
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukuda
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamaguchi
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007014:Hypophosphatasia / Q000453:epidemiology / Q000235:genetics*; D015994:Incidence; D007223:Infant; D008297:Male; D009154:Mutation; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: C548267:ALPL protein, human; D000469:Alkaline Phosphatase
keywords: Bone Disease; Endocrinology; Paediatric Practice