title: Early replacement therapy in a first Japanese case with autosomal recessive guanosine triphosphate cyclohydrolase I deficiency with a novel point mutation.
abstract: Autosomal recessive guanosine triphosphate cyclohydrolase I (GTPCH) deficiency is an inborn error of tetrahydrobiopterin (BH4) synthesis from GTP. GTPCH deficiency causes severe reduction of BH4, resulting in hyperphenylalaninemia (HPA) and decreased dopamine and serotonin synthesis. Without treatment, a patient with GTPCH deficiency develops complex neurological dysfunctions, including dystonia and developmental delays. The first Japanese patient with GTPCH deficiency was discovered by HPA during asymptomatic newborn screening. The phenylalanine level at the age of 5days was 1273μmol/L (cutoff value, 180.0μmol/L). The high serum phenylalanine level was decreased to normal after adequate BH4 oral supplementation. Serum and urinary pteridine examination revealed very low levels of neopterin and biopterin. Sequence analysis of GCH1 revealed compound heterozygous point mutations, including a novel point mutation (p.R235W). Replacement therapy with BH4 and L-dopa/carbidopa were started at the age of 1month, and 5-hydroxytryptophan (5-HTP) was started at the age of 5months. At 10months of age, the patient showed slight dystonia but no obvious developmental delay. Cerebrospinal fluid should be examined to determine the appropriate dosage of supplement drugs. In conclusion, it is important to control the serum phenylalanine level and perform early replacement of neurotransmitters to prevent neurological dysfunction.
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors: Hiroki
authors: H
authors: Sato
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan. Electronic address: uematsu@bk9.so-net.ne.jp.
authors: Mitsugu
authors: M
authors: Uematsu
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors: Wakaba
authors: W
authors: Endo
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors: Tojo
authors: T
authors: Nakayama
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors: Tomoko
authors: T
authors: Kobayashi
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors: Naomi
authors: N
authors: Hino-Fukuyo
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors: Osamu
authors: O
authors: Sakamoto
authors: Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors: Haruo
authors: H
authors: Shintaku
authors: Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
authors: Shigeo
authors: S
authors: Kure
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D015997:Neonatal Screening; D010649:Phenylalanine / Q000097:blood; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D017354:Point Mutation; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001708:Biopterins; D010649:Phenylalanine; D006136:GTP Cyclohydrolase; C003402:sapropterin
keywords: Autosomal recessive guanosine triphosphate cyclohydrolase I (GTPCH); Early replacement therapy; Hyperphenylalaninemia; Tetrahydrobiopterin (BH4)