Background: The 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is the most important type of BH4 deficiency related to hyperphenylalaninemia. It is also accompanied by various neurological signs and symptoms due to impaired synthesis of catecholamines and serotonin. In this report, we aimed to report the long-term results of early initiation of treatment PTPS.
Methods: Between 1988 and 2014, 23 newborns with PTPS deficiency who underwent early treatment at our hospital were identified. All patients received tetrahydrobiopterin replacement in a daily dosage between approximately 2 and 4 mg/kg. The dosages of levodopa replacement were 10 to 15 mg/kg/d, which is considerably higher than the typically recommended dosages of less than 7 mg/kg/d for patients aged younger than 2 years and 8 to 10 mg/kg/d for patients aged 2 years or older. Replacement with 5-hydroxytryptophan varied widely among patients. We examined the IQ score of the patients of age greater than 3 years.
Results: The overall incidence rate of PTPS according to the newborn screen result showed 1/115,000. The mean (SD) IQ score of our PTPS-deficient patients was 96.2 (range, 90-119), which is considerably higher than previous reports of other populations of PTPS-deficient patients (IQ: 76; range, 56-98). All patients reached a normal IQ on high daily dosages of levodopa replacement, without developing apparent long-term levodopa-induced adverse effects. We also observed a correlation between long-term IQ score and genotype, birth weight, and age at initiation of treatment.
Conclusions: An effective newborn screening referral program and early initiation of appropriate therapy preserved the IQ scores of PTPS-deficient patients.
