• Clinical and Experimental Pediatrics
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• v.51 no.5
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• pp.546-550
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• 2008

In this untreated classic phenylketonuria (PKU) case, mental retardation is severe; however, there have been individuals- like the mother of this case- who have escaped mental retardation and all the other potential sequelae of phenylketonuria, despite having high blood phenylalanine levels, and very poor dietary control. It appears that they have nearly normal brain phenylalanine levels despite high blood phenylalanine (Phe) levels. A number of studies have now demonstrated considerable variability in blood vs. brain phenylalanine levels in phenylketonuria patients. Outcome of phenylketonuria appears to be related to brain phenylalanine levels. We report a case of "undiagnosed" maternal phenylketonuria syndrome. A female infant had low birth weight (2,400 g) with microcephaly. We examined her family and discovered that her mother was an undiagnosed phenylketonuria patient with a borderline intelligence quotient (IQ). The infant's sister, six years old, was diagnosed with phenylketonuria at the age of four years was mentally retarded and had received an operation for cleft lip and palate. the sister had also had a low birth weight (2,300 g). Her sister and mother were compound heterozygotes (mother: R243Q/Y325X; sister: Y325X/P407S). The infant and father were heterozygous carriers (baby: R243Q/ -; father: P407S/ - ).

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.24-31
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• 2006

Purpose : The Ministry of Health and Social Affairs adopted newborn screening for the low-income families in 1991 and expanded in 1997 to cover all newborns. At the beginning of the program 6 diseases were selected for screening but the number of screening items had been reduced to two (congenital hypothyroidism and phenylketonuria) from the year 1995. Now, the government program has a fifteen year history. The purpose of this study was to analyze results of neonatal screening tests and prevalence at birth of phenylketonuria and congenital hypothyroidism in Korea. Methods : The results of neonatal screening tests were collected from public health centers during 15 years from 1991 to 2005. These data were analyzed for number of tested newborns and prevalence at birth of the inborn errors of metabolism. Results : Neonatal screening test for inborn error of metabolism was performed for 3,707,773 newborns for 15 years. Among newborns who were screened 718 congenital hypothyroidisms and 86 phenylketonurias were detected, and these presented an prevalence at bith of congenital hypothyroidism 1/5,164 and that of phenylketonuria 1/43,114. The total prevalence of two diseases was 1/4,612. Conclusion : National screening program should be expanded to include all items of screening tests for whole newborns and established correct prevalence of other inherited metabolic diseases in Korea.

• Clinical and Experimental Pediatrics
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• v.63 no.2
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• pp.34-43
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• 2020

Phenylketonuria is a disease caused by congenital defects in phenylalanine metabolism that leads to irreversible nerve cell damage. However, its detection in the early days of life can reduce its severity. Thus, many countries have started disease screening programs for neonates. The present study aimed to determine the worldwide prevalence of classic phenylketonuria using the data of neonatal screening studies.The PubMed, Web of Sciences, Sciences Direct, ProQuest, and Scopus databases were searched for related articles. Article quality was evaluated using the Joanna Briggs Institute Critical Appraisal Evaluation Checklist. A random effect was used to calculate the pooled prevalence, and a phenylketonuria prevalence per 100,000 neonates was reported. A total of 53 studies with 119,152,905 participants conducted in 1964-2017 were included in this systematic review. The highest prevalence (38.13) was reported in Turkey, while the lowest (0.3) in Thailand. A total of 46 studies were entered into the meta-analysis for pooled prevalence estimation. The overall worldwide prevalence of the disease is 6.002 per 100,000 neonates (95% confidence interval, 5.07-6.93). The meta-regression test showed high heterogeneity in the worldwide disease prevalence (I²=99%). Heterogeneity in the worldwide prevalence of phenylketonuria is high, possibly due to differences in factors affecting the disease, such as consanguineous marriages and genetic reserves in different countries, study performance, diagnostic tests, cutoff points, and sample size.

• Clinical and Experimental Pediatrics
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• v.48 no.4
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• pp.369-375
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• 2005

Purpose : Many inborn errors of metabolism can be completely cured with early detection and early treatment. This is why neonatal screening on inborn errors of metabolism is implemented worldwide. In this study, a cost-benefit analysis was performed on the neonatal screening of phenylketonuria and congenital hypothyroidism in Korea. Methods : This study included 2,908,231 neonates who took the neonatal screening on phenylketonuria and congenital hypothyroidism in Korea from January 1991 to December 2003. From those neonates, the incidence rates of phenylketonuria and congenital hypothyroidism were measured. Furthermore, based on 495,000 babies born in 2002, were calculated and compared the total costs in case when neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, and when not. Results : If the neonatal screening on phenylketonuria and congenital hypothyroidism is implemented, benefits far exceed costs at a ratio of 1.77 : 1 in phenylketonuria, and 11.11 : 1 in congenital hypothyroidism. In terms of wons, the present neonatal screening on phenylketonuria and congenital hypothyroidism will gain us more than 29 billion wons every year. Conclusion : This study only concerns the monetary aspects of the neonatal screening. Therefore, the benefits of the neonatal screening is underestimated by ignoring precious but not measurable values such as quality of life. However, the present neonatal screening on phenylketonuria and congenital hypothyroidism is found to be beneficial and should continue for the good of the nation as well as that of the patients.

• Journal of Nutrition and Health
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• v.14 no.2
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• pp.59-70
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• 1981

The objective of this study is to induce the primary characteristics of phenylketonuria in infant rats during the first 2 weeks after birth. The critical biochemical parameter in the development of phenylketonuria is the elevation of plasma phenylalanine while tyrosine is maintained at a relatively low level. A PKU-like condition was induced in infant rats during the first 2 weeks after birth using a modification of our previously published procedure for the development of a temporary (1 to 3 days) PKU-like condition. Phenylalanine was administered by stomach intubation every 6 hours (starting at 6:00 a.m.) at a dose level of 400mg per kg body weight (after birth-day 2 thru 5) and 500mg per kg body weight (day 6 thru 14). Amethopterin was given at 0.00625 or 0.0125mg per kg body weight (day 3 thru 14) and p-chlorophenylalanine at 50 mg per kg body weight (day 5 thru 14) at 9:00 a.m. and 9:00 p.m. At the times measured (6,10 and 14 days) plasma phenylalanine/tyrosine (P/T) ratios were elevated from a normal value of the or less to values ranging from 6 to 15. During the second week after birth a staggering gait, abnormal stance and decreased social behavior were also observed. None of these PKU-like characteristics were apparent in the three control groups receiving (a) no phenylalanine or inhibitors, (b) phenylalanine alone, or (c) inhibitors alone. The establishment of these primary biochemical characteristics of phenylketonuria by stomach intubation of phenylalanine and a combination of low dose levels of enzyme inhibitors to infant rats provides an experimental system which should he valuable for extensive biochemical, histological and behavioral studies in phenylketonuria.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.104-110
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• 2009

Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutations in the phenylalanine catabolic enzyme, phenylalanine hydroxylase (PAH). The use of phenylalanine ammonia-lase (PAL) by oral and parenteral routes as a therapeutic drug for PKU has been severely limited due to inactivation by intestinal proteolysis and immune reactions. PEGylation was applied to PAL to reduce the degrees of antigenicity and proteolytic inactivation. Kinetic experiments with native PAL and pegylated PALs were performed, and pH stability, temperature stability, and protease susceptibility were evaluated. Enzyme linked immunosorbent assay (ELISA) was carried out to measure the immune complex between pegylated PALs and antiserum that had been extracted from a PAL-immunized mouse. Pegylated PAL, especially branched pegylated PAL (10 kDa, 1:32), was more active for phenylalanine and more stable in pancreatic proteases than native PAL. Native PAL was optimal at pH 8.5, corresponding to the average pH range of the small intestine; the same finding was noted for pegylated PALs. All linear and branched pegylated PALs had low reactivity with mouse antiserum, especially the 1:16 formulation with linear 5-kDa PEG and the 1:32 formulation with branched 10-kDa PEG. Therefore, we suggest the 1:32 formulation with branched 10-kDa PEG as the most promising formulation for enzyme replacement therapy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.29-34
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• 2002

• Proceedings of the Korean Nutrition Society Conference
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• 2001.05a
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• pp.236.1-236
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• 2001

• Journal of The Korean Society of Inherited Metabolic disease
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• v.4 no.1
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• pp.5-12
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• 2004

Purpose Phenylketonuria is an inborn error of metabolism, which is inherited as an autosomal recessive trait. PKU is resulting from deficiency of phenylalanine hydroxylase. PAH gene spans about 90 kb on chromosome 12q and comprises 13 exons. In order to define the genetic basis of PKU and the frequencies and distribution of PAH mutations in the Korean population, we analyzed PAH gene in independent 80 patients with PKU. Methods All 13 exons including exon-intron boundaries and 2 kb of 5' upstream region of the PAH gene were analyzed by PCR-direct sequencing methods. Results PAH gene analysis revealed 39 different mutations including 10 novel mutations. The novel mutations consisted of 9 missense mutations (P69S, G103S, N207D, T278S, P281A, L293M, G332V, S391I and A447P) and a novel splice site variant (IVS10-3C>G). R243Q, IVS4-1G>A, and E6-96A>G were the most relevant mutations and they accounted in the whole for 38% of the mutant alleles identified in this study. We also observed that. $BH_4$ responsibility was. associated with genotype of R241C, R53H and R408Q. Conc1ustion Our present study with 80 participants extends the previous results to more comprehensive understanding of PAH allele distribution and frequency in Koreans. Although Korean mutation profile of PAH is similar to those of the nearest oriental populations (Japanese, Chinese, and Taiwanese), several different characteristic features are revealed. The characterization of the genotype-phenotype relationship was also performed. Our data would be very useful information for diagnosis, genetic counseling and planning of dietary and therapeutic strategies in Korean PAH patients.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.89-94
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• 2002

Purpose : This study was performed to determine the safety and efficacy of recently developed specific formulas for phenylketonuria(PKU) patient by observing the growth and developmental pattern and serum phenylalanine level. Methods : We observed 14 patients diagnosed with PKU at Soon Chung Hyang University Hospital fed with formula for 1 year by checking daily diet diary and plasma aminoacids, Hb, Hct, WBC, Platelet count, ferritin, GOT, GPT, protein, albumin, globulin and urinalysis. Results : The 14 patients all liked the formula and height, weight and head circumference showed normal growth. Hemoglobin levels were in normal range, but 4 out of the 14 patients showed ferritin level lower than 12 ng/mL and needed iron supplements. Serum albumin, liver enzyme levels, urinalysis showed within normal range. The plasma phenyalanine levels were normal ranged 0.7-15.6 mg/dL. Adverse reactions such as rash, diarrhea or constipation were not observed. Conclusion : We confirmed that the specific formulas for PKU patients developed in Korea, PKU-1 and PKU-2 showed favorable results In development and treatment of PKU patients and could be used safely to children.