Pre-analytical Considerations

  • CSF must be collected via lumbar puncture under standardized conditions.
  • Collect at least 1–2 mL in polypropylene tubes, ideally from the L3/L4 or L4/L5 space, avoiding traumatic tap.
  • Freeze immediately at –80°C if not analysed promptly.
  • Paired blood samples are often helpful.

Key CSF Neurotransmitter Metabolites & Normal Values


MetaboliteNormal Range (Approximate)*Clinical Significance
5-HIAA (5-Hydroxyindoleacetic Acid) 40–120 nmol/L Major serotonin metabolite. ↓ in AADC deficiency, serotonin synthesis defects, or MAO-A deficiency.
HVA (Homovanillic Acid) 150–450 nmol/L Major dopamine metabolite. ↓ in AADC deficiency, tyrosine hydroxylase deficiency, ↑ in MAO-A deficiency, dopamine transporter defects.
HVA:5-HIAA Ratio 1.0–4.0 A high ratio suggests MAO-A deficiency or dopamine transporter defects. A low ratio may occur in serotonin-specific disorders.
MHPG (3-Methoxy-4-hydroxyphenylethyleneglycol) 10–50 nmol/L Norepinephrine metabolite. ↓ in dopamine β-hydroxylase deficiency.
3-OMD (3-O-Methyldopa) <10 nmol/L ↑ in AADC deficiency. Marker of excess L-DOPA methylation.
L-DOPA <10 nmol/L Precursor to dopamine. Elevated in AADC deficiency, aromatic amino acid decarboxylase defect.
5-HTP (5-Hydroxytryptophan) <5 nmol/L ↑ in AADC deficiency, ↓ in tryptophan hydroxylase deficiency.
Neopterin 30–70 nmol/L Marker of immune activation. Very ↑ in AADC deficiency. May help differentiate primary neurotransmitter defects.
Biopterin 10–30 nmol/L Co-factor for tyrosine and tryptophan hydroxylase. Abnormal in BH4 metabolism disorders. ↓ in GTPCH, PTPS, and DHPR deficiency.
Pterin Profile (Neopterin/Biopterin ratio) N/A Characteristic patterns in BH4 pathway disorders.

*Ranges can vary between laboratories; consult reference lab-specific cut-offs.

Clinical Interpretation: Common Patterns

DisorderCSF HVACSF 5-HIAA3-OMDBiopterin/NeopterinNotes
AADC deficiency ↓↓ ↓↓ ↑↑ Normal or ↑ neopterin Severe hypotonia, oculogyric crises, dystonia
Tyrosine hydroxylase deficiency ↓↓ Normal Normal Normal Infantile parkinsonism, dopa-responsive dystonia
GTPCH deficiency ↓↓ ↓↓ Normal ↓ biopterin Dopa-responsive dystonia, treatable with BH4
MAO-A deficiency ↑ HVA & 5-HIAA ↑↑ Normal Normal Aggression, developmental delay, ↑ HVA:5-HIAA ratio
Dopamine transporter defect (DAT) ↑ HVA Normal Normal Normal Paroxysmal dystonia, oculogyric crises
DHPR deficiency ↓ HVA & 5-HIAA ↓↓ ↑ phenylalanine ↓ biopterin May present like PKU, also affects neurotransmitters

When to Suspect a Neurotransmitter Disorder

  • Early-onset movement disorders (dystonia, parkinsonism, chorea).
  • Recurrent oculogyric crises.
  • Autonomic dysfunction (hypersalivation, temperature instability).
  • Treatment-refractory epilepsy.
  • Profound hypotonia with preserved cognition.
  • Unexplained developmental regression.

Relevant Tests to Combine

  • Plasma amino acids.
  • Serum prolactin (elevated in dopamine deficiency).
  • Urine purines/pyrimidines.
  • Genetic testing (targeted panels or WES).