Prevalence of inherited neurotransmitter disorders in patients with movement disorders and epilepsy: a retrospective cohort study

Orphanet J Rare Dis. 2015 Feb 8;10:12. doi: 10.1186/s13023-015-0234-9.


Background: Inherited neurotransmitter disorders are primary defects of neurotransmitter metabolism. The main purpose of this retrospective cohort study was to identify prevalence of inherited neurotransmitter disorders.

Methods: This retrospective cohort study does not have inclusion criteria; rather included all patients who underwent cerebrospinal fluid (CSF) homovanillic and 5-hydroxyindol acetic acid measurements. Patients with CSF neurotransmitter investigations suggestive of an inherited neurotransmitter disorder and patients with normal or non-diagnostic CSF neurotransmitter investigations underwent direct sequencing of single gene disorders.

Results: There were 154 patients between October 2004 and July 2013. Four patients were excluded due to their diagnosis prior to this study dates. Two major clinical feature categories of patients who underwent lumbar puncture were movement disorders or epilepsy in our institution. Twenty out of the 150 patients (13.3%) were diagnosed with a genetic disorder including inherited neurotransmitter disorders (6 patients) (dihydropteridine reductase, 6-pyruvoyl-tetrahydropterin synthase, guanosine triphosphate cyclohydrolase I, tyrosine hydroxylase, pyridoxine dependent epilepsy due to mutations in the ALDH7A1 gene and pyridoxamine-5-phosphate oxidase deficiencies) and non-neurotransmitter disorders (14 patients).

Conclusion: Prevalence of inherited neurotransmitter disorders was 4% in our retrospective cohort study. Eight out of the 150 patients (5.3%) had one of the treatable inherited metabolic disorders with favorable short-term neurodevelopmental outcomes, highlighting the importance of an early and specific diagnosis. Whole exome or genome sequencing might shed light to unravel underlying genetic defects of new inherited neurotransmitter disorders in near future.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dystonic Disorders / congenital*
  • Dystonic Disorders / diagnosis
  • Dystonic Disorders / genetics
  • Epilepsy / genetics*
  • Epilepsy / metabolism
  • Gene Expression Regulation / physiology*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / genetics*
  • Movement Disorders / genetics*
  • Movement Disorders / metabolism
  • Retrospective Studies
  • Young Adult