Short prolactin profile for monitoring treatment in BH4 deficiency.

Tetrahydrobiopterin (BH4) deficiency causes hyperphenylalaninemia and impaired synthesis of serotonin and dopamine, leading to brain degeneration and early death if left untreated. Replacement therapy with neurotransmitters precursors is the cornerstone of treatment, relying on 5-hydroxytryptophan and L-dopa administration. Effective restoration of dopaminergic activity is thickened, like in Parkinson's disease, by the pulsatile pharmacokinetic profile of L-dopa. Monitoring of L-dopa therapy in BH4 deficiency is generally based upon clinical observation and periodical measurement of homovanillic acid (HVA) concentration in the cerebrospinal fluid (CSF). According to the finding that dopamine is the natural inhibitor of prolactin (PRL) incretion, we introduced the use of peripheral PRL measurement as an index of dopaminergic homeostasis, so avoiding the need of repeated lumbar punctures in patients with BH4 deficiency. As a single PRL evaluation can be misleading, due to the dependency of PRL fluctuations on L-dopa administration schedule, here we show that a short PRL profile is suitable for monitoring these patients. Together with the assessment of patients' clinical symptoms, this standardized tool will ensure an objective non-invasive reference to the management of dopaminergic replacement therapy in BH4 deficiency, even in patients treated with dopamine agonists.