Journal of the Korean Pediatric Society 1993;36(12):1681-1690.
Published online December 15, 1993.
Pterin & DHPR Measurement and DNA Analysis in Korean PKU Patients
Chol Hee Chong1, Hye Yong Lee1, Dong Hwan Lee1, Sang Jhoo Lee1, Ki Weon Cha2, Jeong Bin Yim2, Yoshiyuki Okano3
1Department of Pediatrics, College of Medicine, Soonchunhyang University, Seoul, Korea
2Department of Microbiology, College of National Sciences, Seoul National University, Seoul, Korea
3Department of Pediatrics, Oska City University, Osaka, Japan
한국 페닐케톤뇨증 환자에서 Pterin, DHPR의 측정과 DNA분석
정철희1, 이혜용1, 이동환1, 이상주1, 차기원2, 임정빈2, Y. Okano3
1순천향대학교 의과대학 소아과학교실
2서울대학교 의과대학 미생물학과
3Department of Pediatrics, Oska City University, Osaka, Japan
Abstract
Phenylketonuria in metabolic disorder that results from a deficiency of the hepatic phenylalanine hydroxylase. But among patients with hyperphenylalaninemia, the defect resides in one of the enzymes necessary for production or recycling of tetrahydrobiopterin (BH4). The reduction of BH4 affects not only phenylalanine metabolism but also formation of the tyrosine related neurotransmitter, dopamin and tryptophan related neurotransmitter, serotonin. Administration of L-dopa and 5-hydroxytriptophan seems to be the most effective treatment and may prevent irreversible neurologic damage if started early in life in hyperphenylalaninemia due to deficiency of cofactor BH4. Therefore, all patients with PKU and hyperphenylalaninemia should be tested for BH4 deficiency as early as passible. So we measured reduced forms of biopterin in urines of 19 phenylketonuria patients by Funkushima and Nixon method and 13 of PKU patients measured dihydropterin reductase (DHPR) in white blood cells by modified Narisawa method. We could not find abnormal pterin patterns of cofactor BH4 and normal value of DHPR. All Korean 19 PKU chidren were classic PKU. A missense mutation has been identified in the phenylalanine hydroxylase (PAH) gene of 16 Korean PKU patients. 5 mutations (IVS4, Y204 C, R243Q, Y356 P) have been identified. The frequency of these mutations was found to be 50% of PKU alleles. The IVS4 mutation had a high frequency in Korea and southern China, due to the result of the founder effect and genetic drift. The R413 P mutation, which may have originated in the regions surrounding the Baikal, expanded to northen China and Japan. We were not able to find Caucasian mutations in Korean ptiets. PKU mutations occured after racial divergence between Caucasian and Mongoloids. We observed that PKU patients with Y204 C and R413 P mutations showed mild clinical phenotype but IVS4 mutation had severe mental retardation. The establishment of genotype will therefore aid in the prediction of clinical phenotypes in patients with this disease. So, pterin and DHPR measurement and DNA analsis will be useful for prognosis and proper treatment of PKU patients.
Key Words: Phenylketonuria, Tetrahydrobiopterine (BH4), Phenylalanine hydroxylase, Mutation


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