• Journal of Genetic Medicine
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• v.5 no.2
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• pp.111-118
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• 2008

Purpose: Neonatal screening tests are increasingly being used forearly diagnosis of inborn errors of metabolism (IEM) in the hope of avoiding the severe developmental delay, acute illness, and death that may result from these diseases. In this study, a cost-benefit analysis was performed on the neonatal screening of maple syrup urine disease, homocystinuria, galactosemia, and congenital adrenal hyperplasia in Korea. Materials and Methods: This study included 1,259,220 Korean newborns born between January 2005 to December 2007, who were screened for maple syrup urine disease, homocystinuria, galactosemia, and congenital adrenal hyperplasia. We calculated and compared the total costs in cases where these four screening tests were implemented, and those where they were not. Results: There were no benefits to screening for maple syrup urine disease or homocystinuria due to their low prevalence for these two tests, the costs exceeded the benefits at benefit:cost ratios of 0.5:1 and 0.6:1, respectively. In contrast, benefits far exceed costs at a ratio of 4.1:1 for galactosemia and 2.9:1 for congenital adrenal hyperplasia. The average benefit:cost ratio for all four tests was 2.0:1. Conclusion: Neonatal screening tests for maple syrup urine disease, homocystinuria, galactosemia, and congenital adrenal hyperplasia are financially viable.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.101-109
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• 2015

Classic galactosemia (OMIM #230400) is an autosomal recessive inherited metaboic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) due to mutations in the GALT gene. If untreated, classic galactosemia is a potentially lethal disease presenting with poor feeding, vomiting, jaundice, liver failure, increased bleeding tendency, and septicemia leading to death within a few days after birth. Since 2006, expansion of newborn screening has been enabled the early diagnosis and early intervention of classic galactosemia in Korea. However, newborn screening, followup testing for confirmatory diagnosis and intervention for galactosemia continue to present challenges. In Korea, the prevalence of the classic galactosemia is considered relatively low compared to that of western countries. And the genotype is also clearly different from those of other population. Therefore, our own guideline for confirmatory diagnosis and intervention is needed. Here, the diagnostic algorithm for galactosemia after positive newborn screening result in Korea has been proposed. Considering the low prevalence and different mutation spectrum in Koreans, the early mutation analysis of GALT gene could be a useful tool for the accurate diagnosis and making any treatment decision.

• Proceedings of the KAIS Fall Conference
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• 2009.05a
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• pp.599-602
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• 2009

본 연구는 2006년 3월부터 2007년 2월까지 일개 대학병원에서 출생한 고위험군 신생아 121명을 대상으로 청각선별검사인 자동화 유발이음향방사와 확진검사인 청성뇌유발전위검사를 실시하여 임상양상과 청각장애 발생률, 검사소요 시간에 대해 조사하였다. 결과는 다음과 같다. 1. 청각장애발생률은 전체 고위험군 신생아 121명 중 5명의 신생아가 난청으로 조기에 진단되었다. 2. 난청으로 확진 받은 신생아 5명의 관련 질병을 살펴보면 고빌리루빈혈증 2명, 저체중 1명, 구개열 1명, 다운증후군 1명이었다. 3. 난청으로 확진 받은 신생아 5명의 청력손실정도는 양측 고도난청 1명(70dB), 양측 중도난청 2명(55dB), 편측성 난청 2명으로 나타났다. 4. 검사소요 시간은 선별검사인 유발이음향방사 검사를 실시하는 데 소요된 총 시간의 평균은 $107.5{\pm}65.2$초였고, 확진검사인 청성뇌유발전위 검사를 실시하는 데 소요된 총 시간의 평균은 $1,500{\pm}90.1$초가 소요되었다. 5. 연구를 진행하는 도중 11명의 고위험군 신생아가 이사, 연락처 변경, 경제적 사정으로 추적검사에 참여하지 않았다. 신생아 난청은 다른 질병에 비해 발병률이 높은 선천성 질환으로서 모든 신생아를 대상으로 청각검사를 실시하여 난청의 조기진단에 대한 선별검사의 정착이 필요하다고 생각된다.

• Clinical and Experimental Pediatrics
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• v.49 no.10
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• pp.1056-1060
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• 2006

Purpose : As hearing ability affects language and cognitive development, early detection and intervention of congenital hearing defects is very important. We analyzed the result of newborn hearing screening using automated auditory brainstem response and estimated the incidence of congenital hearing defects in newborn infants in Korea. Methods : Hearing screening tests were done on 7,218 newborn infants who were delivered at Cheil General Hospital from July 1, 2004 to June 30, 2005. The first screening test was done on the second day of life with automated auditory brainstem response(AABR) using $ALGO{\bigcirc}^{(3)}$ Newborn hearing screener($Natus^{(R)}$ Medical Incorporated, San Carlos, USA) with 35 dB sound level. The newborn infants who did not pass the initial screening test took the second screening AABR test before discharge from the nursery. Infants who did not pass these screenings at the nursery were followed up at the Department of Otorhinolaryngology, Samsung Seoul Hospital. Results : Total 7,218 infants(83.3 percent of total 8,664 live births of the Cheil General Hospital) were screened in the nursery, and 55 of them failed to pass the newborn screening. Among 55 infants who were referred, six were lost during follow-up, and 14 were confirmed as hearing impaired. Six of them(42.8 percent) do not have any risk factors for hearing impairment. We can estimate that the incidence of hearing defects is about 1.9-2.8 per 1,000 live births. Conclusion : Automated auditory brainstem response is an effective tool to screen the hearing of newborn infants. Congenital hearing loss is more frequent than metabolic diseases on which screening tests are available in the newborn period. About 40 percent of infants who have hearing defects do not have any risk factors for hearing impairment. Therefore, universal newborn hearing screening must be recommended to all neonates.

• Clinical and Experimental Pediatrics
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• v.48 no.4
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• pp.387-394
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• 2005

Purpose : We performed this study to compare the TSH and free $T_4$ levels according to gestational age and birth weight, and to reevaluate the cut-off values in the neonatal screening test for congenital hypothyroidism. Methods : Total 2,133 neonates(1,749 healthy newborns and 384 sick neonates) were screened in Dankook University Hospital from May 2000 to January 2003. Neonates with abnormal TSH values (higher than $20{\mu}IU/mL$) or abnormal free $T_4$ levels(lower than 1 ng/dL) were recalled to recheck the thyroid function test. At that time, physical examinations and history-taking regarding perinatal problem, medication history, and mother's illness were undertaken. Results : Serum TSH and free $T_4$ values revealed no significant difference according to sex, delivery type, and Apgar score. The free $T_4$ levels showed statistically significant differences, with gestational age or birth weight(P<0.01). The recall rate of neonates due to abnormal screening test was 7.48 percent. Compared with original cut-off values, the recall rate of the new cut-off values setted to TSH higher than $20{\mu}IU/mL$ or free $T_4$ lower than 0.64 ng/dL decreased from 7.48 percent to 4.8 percent in the healthy group. But, it compromised sensitivity when applied to the sick group. Conclusion : In this study, neonatal free $T_4$ levels were significantly different according to birth weight, gestational age, and the presence of compromised condition. Although the recall rate by TSH > $20{\mu}IU/mL$ or free $T_4$ <1 ng/dL was relatively high, it was impossible to set up new cut-off values without compromising sensitivity. We think studies including a larger study population will be required to change the cut-off values.

• Journal of Genetic Medicine
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• v.5 no.1
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• pp.21-25
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• 2008

Purpose : In recent years, many countries have adopted newborn screening programs that use tandem mass spectrometry (MS/MS) to screen and the number of diseases screened has also increased. We began screening for inherited metabolic disorders using MS/MS in April, 2001. Our goal was to determine the overall prevalence of metabolic disorders and to assess the effectiveness of newborn screening by MS/MS in Korea. Methods : From April, 2001 to December, 2007, we screened newborns and high risk groups using MS/MS. Acylcarnitines and amino acids were extracted and butylated and were introduced into the inlet of MS/MS. Confirmatory testing including a repeat newborn screening, and urine organic acid and plasma amino acid analysis were performed on a case-by-case basis. Results : The total number of screened subjects 284,933 which comprised 251,799 neonates and 33,134 high risk subjects. The recall rate was 0.4% (1158 tests) and true positive cases were 117 (0.04%). Confirmed metabolic disorders (newborn/high risk group) were as follows; 78 (25/53) amino acid disorders, 27 (16/11) organic acid disorders, and 12 (5/7) fatty acid oxidation disorders. The estimated prevalence of inherited metabolic diseases in newborns was 1:5,000 and that in the total group was 1:2,000. Conclusion : Newborn screening by MS/MS improved the detection of many inherited metabolic disorders. We therefore propose that all newborns be screened by a MS/MS national program and followed-up using a systemic organization strategy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.2
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• pp.70-78
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• 2016

21-hydroxylase deficiency (21-OHD), most common form of congenial adrenal hyperplasia, is categorized into classical forms, including the salt-wasting (SW) and the simple virilizing (SV) types, and nonclassical (NC) forms based on the severity of the disease. Newborn screening for 21-OHD has been performed in Korea since 2006. $17{\alpha}$-hydroxyprogesterone (17-OHP) is a marker for 21-OHD and is measured using a radioimmunoassay or a fluoroimmunoassay. Premature and low birth weight infants are likely to give false positive 17-OHP findings, therefore, cutoff values for these infants should be determined based on gestational weeks or birth weight. ACTH simulation test is helpful when the 17-OHP shows equivocal increase, and it is gold standard for diagnosis of NC type. Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes. Molecular analysis of CYP21A2 is useful for confirming diagnosis of mild SV or NC type, predicting prognoses, and genetic counseling. In order to make newborn screening for 21-OHD more efficient, early detection of boy with SW type, early determination of girl with ambiguous genitalia, detection of NC type, and overcoming of false positive in premature and low birth weight infants should be considered. Above all, early treatment should be started when the patient is suspected as having 21- OHD clinically before confirming the diagnosis to prevent adrenal crisis. Here, author reviewed recent articles of guideline and proposed guideline for 21-OHD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.1-9
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• 2016

Newborn screening (NBS) is important if early intervention is effective in a disorder and if there are sensitive and specific biochemical markers to detect disorder. Methionine is a useful marker to detect abnormal methionine-homocysteine metabolism, especially homocystinuria which needs urgent medical intervention. However, hypermethioninemia could occur in other metabolic disorder including liver disease, tyrosinemia type I, methionine adenosyltransferase (MAT) I/III deficiency, glycine N-methyltransferase (GNMT) deficiency, or adenosylhomocysteine hydrolase deficiency. However, experience with NBS for homocystinurias and methylation disorders is limited. Especially, MAT I/III deficiency which is the most common cause of persistent hypermethioninemia have two inheritance, autosomal recessive (AR) and autosomal dominant (AD), and their clinical manifestation is different between AR and AD. Here, author reviewed recent articles of guideline and proposed guideline for homocystinuria and methylation disorder.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.2
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• pp.99-103
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• 2012

Tyrosinemia type I is an autosomal recessive inborn error of tyrosine metabolism that caused a mutation. Clinical symptoms include progressive liver damage with liver failure, coagulopathy, hypophosphataemic rickets, renal tubular dysfunction and a high risk of hepatocellular carcinoma. If left untreated, the affected infants may die from liver failure within the first year of life. PharmacoloIcal therapy with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) has offered an effective therapeutic option in addition to dietary restriction of tyrosine and phenylalanine. As prognosis of tyrosinemia type I is improving with early diagnosis and early treatments, it meets the criteria for a condition that would benefit from newborn screening. We report a case of tyrosinemia type I diagnosed by newborn screening and successive biochemical analysis of plasma and urine, treated by dietary restriction and NTBC.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.19 no.1
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• pp.1-11
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• 2019

Purpose: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. The purpose of the present study was to determine the incidence of CH in South Korea during the period from January 1991 to March 2004. Methods: Central data from each city branch of SCL (Seoul Clinical Reference Laboratories) in Yongin, South Korea, was gathered and collectively analyzed. Newborn screening (NBS) for CH was based on measuring the levels of neonatal thyroid stimulating hormone (TSH) and free T4 (a cut-off of 20 mIU/L and less than 0.8 ng/dL, respectively). Results: During the study period, 671,805 live births were screened for CH based on TSH and free T4 ELISA assays. A total of 159 newborns were deemed positive for CH out of 671,805, with a corresponding incidence of 1 in 4,225. When a cut-off of 20 mIU/L was used in TSH assays, the associated sensitivity, specificity, and positive predictive values (PPV) were 100.0%, 99.7%, and 10.8%, respectively. When a cut-off of 0.8 ng/dL in free T4 assays was used, the associated sensitivity, specificity, and PPV were 100.0%, 98.5%, and 3.9%, respectively. Conclusion: CH incidence in South Korea as evidenced by the results of NBS was compared with its incidence and comparable to the other countries prior to 2004.