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

Summary Tetrahydrobiopterin (BH4) deficiency is an autosomal recessive disorder caused by enzyme defects in the biosynthesis or recycling of BH4. Patients with BH4 deficiency present with severe neurological signs and symptoms and .require a different treatment from classical phenylketonuria. During the last 12 years, 31 cases of BH4 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 BH4, 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.