ABSTRACT
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 1week, 1month, 6months, 1year, 3years and 15years were 35.0, 31.0, 26.0, 24.0, 21.0 and 17.0µmol/L respectively. Assessment of CSF serine concentrations in 11 patients (aged 1day to 13years) previously diagnosed with disorders of serine biosynthesis (serine concentrations ranging from 5 to 18µmol/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 12.6-69.4µmol/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.
