Delayed Diagnosis in Child with Tetrahydrobiopterin deficiency (BH4) syndrome

초록

Introduction Dopamine response dystonia (DRD) shows similar to cerebral palsy initially, but represents improvement of dystonia with the dopamine. DRD can result from several distinct enzymatic defects within the dopamine biosynthetic pathway, including tetrahydrobiopterin (BH4) deficiencies. The estimated incidence of BH4 deficiencies is about 0.0001%. Thus, we report a very rare case with DRD induced by one of BH4 deficiency syndrome. Case Report In 1990, a boy was born with 3.2kg at 40 weeks by normal delivery without significant medical history. However, he showed delayed development with hypotonia, seizure, dysphagia, and drooling. At 2 years old, He was diagnosed with cerebral palsy and had undergone rehabilitation therapy at another hospital. At a years of 9, he visited our hospital for further evaluation about diurnal fluctuation of abnormal movements with heavy sweating and drooling. Brain MRI and the electrodiagnostic study showed non specific finding. To rule out DRD, he was administered L-dopa trial. Then his poor balance and dyskinetic movements were much improved, so we diagnosed him DRD. We recommended the genetic test but they refused it for economic reasons. He took Sinemet® from 1999 to 2019. When he skipped the medication, he could not stand and walk at all. The administration of Sinemet® made him to do the activities of daily living with minimal assist. In 2019, when he was 29 years old, at amino acid test, the phenylalanine level was high (687 nmol/mL; normal value 35~85). At urine test, the neopterin and biopterin were 5.87 and 0.18 mmol/mol crea, respectively.% biopterin was very low (2.93%; normal value 44~77%) (Table 1). In the NGS test, we found a homogeneous PTS (6-pyruvoyl tetrahydropterin synthase, PTPS) gene mutation at Chromosome 11 (c.259C>T). Sanger sequencing gene study of his family showed all family (father, mother and sister) had heterozygotic mutation of the same type with him (Table 2).