Multicentre age-related reference intervals for cerebrospinal fluid serine concentrations: Implications for the diagnosis and follow-up of serine biosynthesis disorders

Research output: Contribution to journalArticle


The disorders of serine biosynthesis are a group of inborn errors of metabolism characterised by congenital microcephaly, seizures and severe psychomotor retardation. Although these disorders are rare the prompt recognition of serine deficiency is important as these disorders are treatable. The diagnosis is based on decreased concentrations of serine in cerebrospinal fluid (CSF). It has previously been reported that CSF serine concentrations are inversely associated with age. However, accurate age-related reference intervals have not been generated which has contributed to cases not being identified. In a multicentre study involving 9 different laboratories a total of 424 CSF serine results were obtained. Regression based analyses were performed to calculate age-specific reference intervals. Lower reference intervals for subjects aged 1. week, 1. month, 6. months, 1. year, 3. years and 15. years were 35.0, 31.0, 26.0, 24.0, 21.0 and 17.0 μmol/L respectively. Assessment of CSF serine concentrations in 11 patients (aged 1. day to 13. years) previously diagnosed with disorders of serine biosynthesis (serine concentrations ranging from 5 to 18 μmol/L) were clearly decreased compared to our age-related reference intervals and would have correctly identified all cases, thus enabling prompt treatment. However, if age had not been taken into consideration a reference interval of 12.6-69.4 μmol/L would be obtained for the combined data set and would have resulted in 2 cases being missed. In conclusion, appropriate age-related reference intervals for CSF serine should be used to diagnose patients with inborn errors of serine biosynthesis.


  • Stuart Moat
  • Rachel Carling
  • Authur Nix
  • Michael Henderson
  • Anthony Briddon
  • Helen Prunty
  • Roy Talbot
  • Annette Powell
  • Katherine Wright
  • Sabine Fuchs
  • Tom de Koning
External organisations
  • University Hospital of Wales
  • Addenbrooke's Hospital
  • Cardiff University
  • St James's University Hospital
  • Sheffield Children's Hospital
  • Birmingham Children's Hospital
  • Alder Hey Children's Hospital
  • University Medical Center Utrecht
  • Royal Free Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • Cerebrospinal fluid, Diagnosis, Reference intervals, Serine
Original languageEnglish
Pages (from-to)149-152
Number of pages4
JournalMolecular Genetics and Metabolism
Issue number2-3
Publication statusPublished - 2010 Oct 1
Publication categoryResearch
Externally publishedYes