Dopamine agonists in 6-pyruvoyl tetrahydropterin synthase deficiency.
OBJECTIVE
To report the efficacy, tolerability, and safety of the dopamine agonist pramipexole in a series of 5 patients affected by inherited 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and needing l-3,4 dihydroxyphenylalanine (l-dopa) therapy.


METHODS
Patients included 4 males and 1 female with ages ranging from 2 to 26 years. Their medication included tetrahydrobiopterin (BH4), 5-hydroxytryptophan, l-dopa, carbidopa, selegiline, and entacapone. All experienced residual symptoms of dopamine deficiency, movement and behavioral disability, and complications of l-dopa therapy, associated with fluctuating hyperprolactinemia. Patients had full assessment of clinical and biochemical condition, including evaluation by an adapted Unified Parkinson's Disease Rating Scale (UPDRS) and measurement of plasma prolactin (PRL) and catecholamines, before and after a 6-week trial with pramipexole. Pramipexole was administered twice daily as an adjunct to l-dopa therapy in dosages upwardly titrated, with a concurrent reduction of l-dopa dosage. Clinical follow-up went on for 1 year.


RESULTS
Pramipexole was well tolerated by all patients, with marked improvement and stabilization of their clinical picture. The mean improvement on the total UPDRS score was 43% (range 33.3%-55.6%) from baseline. Diurnal profiles of plasma PRL normalized and plasma catecholamine levels lasted unchanged. The daily administrations of l-dopa were curtailed from 3 or 4 to 2, and the l-dopa dosage was reduced up to 40%.


CONCLUSIONS
The addition of pramipexole to the treatment of 6-pyruvoyl tetrahydropterin synthase deficiency improves the results of l-3,4 dihydroxyphenylalanine therapy. Similar benefits may be expected in other forms of inherited tetrahydrobiopterin deficiency.
Porta
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Department of Pediatrics, University of Torino, Piazza Polonia 94, 10126 Torino, Italy.
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Concolino
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Spada
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Ponzone
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D000328:Adult; D052160:Benzothiazoles / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018491:Dopamine Agonists / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy / Q000201:enzymology; D019761:Phosphorus-Oxygen Lyases / Q000172:deficiency*; D000077487:Pramipexole; D055815:Young Adult
D052160:Benzothiazoles; D018491:Dopamine Agonists; D007980:Levodopa; D000077487:Pramipexole; D019761:Phosphorus-Oxygen Lyases; C043497:6-pyruvoyltetrahydropterin synthase