Purpose: A deficiency of BH4 (tetrahydrobiopterin) not only causes the classical phenylketonuric phenotype, but also is the source of neurological signs and symptoms due to impaired syntheses of L-Dopa and serotonin. The treatment of BH4 deficiency usually consists of replacement with BH4 and the neurotransmitters. We performed this study to find out long-term follow-up clinical symptoms and prognosis of BH4 deficiency.

Methods: Clinical and biochemical, genetic analysis were done retrospectively from January 2006 to January 2018 in Soonchunhyang University Hospital.

Results: In our study, total 190 patients were confirmed to classic phenylketonuria (PKU), BH4 responsive PKU. Among them, thirteen patients were BH4 deficiency. Eleven patients were 6-pyruvoyl-tetrahydropterin (PTPS) deficiency and one patient was dihydropteridine reductase (DHPR) deficiency. The patients who received delayed treatment, most of our patients suffered from severe psychomotor retardation, hypotonia and seizure. C.259C>T mutation was identified most commonly in PTPS gene analysis. A patient with DHPR deficiency had a mental retardation, dystonia, seizure. His seizure semiology was dialeptic feature. His EEG showed generalized spike wave patterns. Valproic acid had a good effect for his symptoms.

All patients had treated with tolerate L-Dopa and 5-hydroxytryptophan. Most of the early treated (newborn) patients have a good tolerance for drugs well. But some patients had neurologic symptoms, despite early detection and treatment.

Conclusion: We reviewed the clinical findings of BH4 deficiency patients.