A case of 6-pyruvoyl-tetrahydropterin synthase deficiency demonstrates a more significant correlation of L-Dopa dosage with serum prolactin levels than CSF homovanillic acid levels

Brain Dev. 2008 Jan;30(1):82-5. doi: 10.1016/j.braindev.2007.05.011. Epub 2007 Jun 27.

Abstract

6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a tetrahydrobiopterin (BH4) deficiency that presents as hyperphenylalaninemia. Administration of the neurotransmitter precursors L-Dopa/carbidopa and 5-hydroxytryptophan (5HTP), as well as BH4, is necessary for treatment. It has been reported that serum prolactin levels are elevated in patients with PTPS deficiency indicating that inhibition of prolactin secretion by dopamine is insufficient and is negatively correlated with the CSF level of HVA. Here, we present a case of PTPS deficiency which showed a more significant correlation of dosage of L-Dopa/carbidopa with serum prolactin levels than with CSF HVA levels. Combined treatment of BH4, L-Dopa/carbidopa, and 5HTP was started as the CSF neopterin/biopterin ratio (N/B ratio 7.54, control 0.46-1.59) and serum prolactin level (36.79 ng/ml, control <15) were elevated. The dosage of L-Dopa/carbidopa was adjusted in the range of 9.08-10.5mg/kg/day. The CSF level of HVA stayed within normal limits using these dosages of L-Dopa/carbidopa, and there was no correlation between dose given and HVA level (R=0.230, p=0.71). On the other hand, even in this relatively small dosing range, the serum prolactin level showed significant negative correlation with the dosage of L-Dopa/carbidopa (R=0.645, p=0.023). The patient did not show any neurological symptoms even when the serum prolactin level was elevated. From these results, we suggest that the serum prolactin level may be a more sensitive marker than the CSF HVA level to guide the dose adjustment of L-Dopa/carbidopa in the management of patients with PTPS deficiency.

Publication types

  • Case Reports

MeSH terms

  • 5-Hydroxytryptophan / metabolism
  • 5-Hydroxytryptophan / pharmacology
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Biopterins / analogs & derivatives
  • Biopterins / biosynthesis
  • Biopterins / deficiency
  • Biopterins / pharmacology
  • Brain Diseases, Metabolic / blood*
  • Brain Diseases, Metabolic / cerebrospinal fluid*
  • Brain Diseases, Metabolic / drug therapy
  • Child, Preschool
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Homovanillic Acid / blood*
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Levodopa / administration & dosage*
  • Levodopa / metabolism
  • Phosphorus-Oxygen Lyases / deficiency*
  • Phosphorus-Oxygen Lyases / genetics
  • Predictive Value of Tests
  • Prolactin / blood*
  • Prolactin / metabolism

Substances

  • Biomarkers
  • Biopterins
  • Levodopa
  • Prolactin
  • 5-Hydroxytryptophan
  • Phosphorus-Oxygen Lyases
  • 6-pyruvoyltetrahydropterin synthase
  • sapropterin
  • Dopamine
  • Homovanillic Acid