Long-term outcome and neuroradiological findings of 31 patients with 6-pyruvoyltetrahydropterin synthase deficiency.

[classical phenylketonuria]

Tetrahydrobiopterin (BH (4 )) deficiency is an autosomal recessive disorder caused by enzyme defects in the biosynthesis or recycling of BH (4 ). Patients with BH (4 ) deficiency present with severe neurological signs and symptoms and require a different treatment from classical phenylketonuria . During the last 12 years , 31 cases of BH (4 ) deficiency were identified in our department . They were all classified as 6 -pyruvoyl-tetrahydropterin synthase (PTPS ) deficiency . They were diagnosed at the ages of 2 .5 -48 months and treated with BH (4 ), L-dopa and 5 -hydroxytryptophan immediately after diagnosis . The average development quotients (DQ ) at diagnosis and after treatment for more than 3 years were 53 +/- 16 , and 78 +/- 15 , respectively . A significant negative correlation was observed between the level of the DQ and the age at which treatment was commenced (r = -0 .751 , p = 0 .002 ). Developmental profiles were uneven . Language , adaptability and at later age mathematics were particularly weak areas . Only two patients achieved a good performance in mathematics . Eleven patients who were treated with drugs from ages of 2 .9 -48 months had neuroradiological scanning . Computed tomography disclosed calcification in lentiform nuclei in one patient and magnetic resonance imaging disclosed delayed myelination and abnormal high intensity signal in cerebral white matter in all of them . Even though most of abnormalities were reversible , small patchy or spotted areas were still present on these regions after treatment for 10 -46 months . In summary , our study supports the substantial efficacy of the current therapeutic approach in PTPS deficiency of normalizing amine neurotransmitters with three drugs as early as possible . For the first time , calcifications could be detected in patients with PTPS deficiency . Abnormalities in white matter on magnetic resonance imaging were not related to clinical manifestations and most were reversible .