Importance of CSF in the diagnosis of Pediatric Neurotransmitter Disorders and Cerebral Folate Deficiency (CFD)

Objectives: Many neurometabolic disorders can be diagnosed through serum and urine analysis and/or CT/MRI investigations. Nevertheless CSF is the only informative sample for the definite diagnosis of Pediatric Neurotransmitter Disorders or Cerebral Folate Deficiency.

Material and Methods: We investigated CSF samples, gained in standardized manner from patients with suspected impaired biogenic amine neurotransmission or suspected Cerebral Folate Deficiency. Analysis of amino acids, neurotransmitter metabolites and folates was performed by HPLC.

Results: We investigated almost 4000 CSF samples and diagnosed 151 patients with PTPS-deficiency, 81 patients with DHPR-deficiency, 9 patients with GTPCH-deficiency, 6 with SR-deficiency, 22 with DRD (Segawa), 9 with TH-deficiency und 7 with AADC-deficiency. Additionally 31 patients with recently described Cerebral Folate Deficiency (CFD) were identified by decreased 5MTHF level in CSF. 5MTHF deficiency was also found in 8 out of 15 patients with Rett syndrome, 32 patients with DHPR-deficiency and 3 out of 5 patients with Aicardi-Goutierès syndrome.

Conclusions: Many clinical signs and symptoms are not specific for a single neurometabolic disorder. For definite diagnosis and early therapy extensive biochemical investigations are essential. CSF analysis should be considered in patients presenting with typical clinical symptoms like unclear psychomotor retardation, microcephaly, cerebellar ataxia, hypo- or dyskinesias, myoclonic epilepsy or hypersalivation to clarify Neurotransmitter Disorders or Cerebral Folate Deficiency.