title: A Diagnostic Algorithm for Children with Low Alkaline Phosphatase Activities: Lessons Learned from Laboratory Screening for Hypophosphatasia.
abstract: To explore the role of laboratory screening for hypophosphatasia and propose a diagnostic pathway for children with low serum alkaline phosphatase (ALP) activities.
  
  
  
  A retrospective hospital-based study over an 8-year period was conducted to identify children younger than 16 years of age with low ALP activity (<100 U/L). Study-positive patients were contacted for repeat sampling, and those with persistently low ALP had plasma pyridoxal-5'-phosphate and urinary phosphoethanolamine measured.
  
  
  
  Of 323 064 analyzed samples, 1526 had ALP activities <100 U/L. Most patients had transient hypophosphatasemia. Of 50 patients with last-recorded ALP <100 U/L, 32 were excluded given previous ALP >100 U/L. Eighteen were identified as study-positive. Of the 15 surviving children, 13 were traceable. Four had persistently low ALP activity on retesting, of whom 2 had raised pyridoxal-5'-phosphate and phosphoethanolamine concentrations and were subsequently tested for ALPL gene mutations; a 4-year-old asymptomatic girl with a novel homozygous ALPL missense mutation and a 23-year-old female with a heterozygous mutation. There was significant overlap in ALP activities between study-positive and 11 current patients with hypophosphatasia. We propose a diagnostic algorithm for children with low ALP activities based on clinical and biochemical variables.
  
  
  
  Patients with persistently low ALP activity require further clinical, biochemical, and radiological assessment for hypophosphatasia, even in the absence of clinical symptoms. The proposed diagnostic algorithm for children with low ALP will facilitate early detection of cases of hypophosphatasia, which, with the availability of enzyme replacement for hypophosphatasia, can be life-saving or avoid years of undiagnosed morbidity.
authors.affiliation: Department of Endocrinology and Diabetes, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Vrinda
authors.initials: V
authors.lastname: Saraff
authors.affiliation: Department of Endocrinology and Diabetes, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Vidya K
authors.initials: VK
authors.lastname: Narayanan
authors.affiliation: Department of Biochemistry and Immunology, Birmingham Heart of England Foundation Trust, Birmingham, United Kingdom; Newborn Screening and Biochemical Genetics, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Lawson
authors.affiliation: Department of Endocrinology and Diabetes, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shaw
authors.affiliation: Newborn Screening and Biochemical Genetics, Birmingham Children's Hospital, Birmingham, United Kingdom.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Preece
authors.affiliation: Department of Endocrinology and Diabetes, Birmingham Children's Hospital, Birmingham, United Kingdom. Electronic address: wolfgang.hogler@bch.nhs.uk.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Högler
mesh_terms: D000293:Adolescent; D000465:Algorithms; D000469:Alkaline Phosphatase / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008403:Mass Screening / Q000379:methods*; D009154:Mutation; D012189:Retrospective Studies
chemical_list: D000469:Alkaline Phosphatase