• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.31-38
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• 2023

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder caused by a deficiency in branched chain α-keto acid dehydrogenase (BCKAD). Between 1997, when Korea's MSUD case was first reported, and 2023, 14 cases were reported in the literature. 29% of the cases experienced developmental delay, and 29% expired. The prevalence of MSUD in Korea was estimated to be 1 in 230,000. Of 21 MSUD patients currently being treated at the Korea Genetics Research Center, 19 were detected through newborn screening program, and 2 were diagnosed by the symptoms. 14 MSUD patients had confirmed genetic mutations; 6 (43%) were BCKDHA and 8 (57%) were BCKDHB. In one case, a large deletion was observed. 4 patients had leucine levels above 2,000 (umo/L), and post-dialysis diet therapy was initiated in the newborn period. No patient required further dialysis as diet therapy and regular monitoring proved highly effective. Most MSUD patients were growing normally; weight and height growth were above the 50th percentile in 76% of the cases while BMI values were higher than normal in 71% of cases. Developmental delays were observed only in 2 cases (10%) and anticonvulsant use in 3 cases (14%). With newborn screening available to all Korean infants, early diagnosis and intervention should allow most patients to remain asymptomatic. However, ongoing surveillance, dietary management and continued patient compliance as well as rapid correction of acute metabolic decompensations remain critical to a favorable long-term prognosis.

• Childhood Kidney Diseases
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• v.3 no.1
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• pp.57-63
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• 1999

Purpose : To evaluate the diagnostic significance of simultaneous examination of hematuria and proteinuria in the urinary mass screening for early detection ot incipient renal diseases. Method and Object : During the period of 4 months from August to December in 1997, we did urinary mass screening on students of first grade of high school (16 years aged group) nationwide together with Korean Association of Health(KAH). In the first screening test, Comber-10 $N^{(R)}$ M dipsticks were used to detect proteinuria, hematuria, pyuria and nitrite simultaneously. Total 26,508 students (16 years aged group) from 33 high schools in every province in Korea, respectively, complied to the urinary mass screening. After then, one high school in Seoul was selected to reveal the true incidence of incipient renal diseases among students who showed hematuria in the initial screening through intensive examinations. Those who had hematuria and/or proteinuria visited the Paik hospital, and underwent blood tests and ultrasonographic examinations. The results were evaluated. Results 1) The initial screening revealed that the prevalence of proteinuria, hematuria, pyuria and positive nitrite urine, were $0.73\%,\;2.69\%,\;0.23\%\;and\;0.03\%$, respectively. 2) The first urinary screening among 875 students from one high school in Seoul selected fir the second test showed proteinuria, hematuria, pyuria and positive nitrite urine, were $0.91\%,\;4.68\%,\;0.34\%\;and\;0\%$, respectively. a) Total 8 among 875 students showed proteinuria, but one of them had orthostatic proteinuria and those remaining 7 students had transient proteinuria. b) There were 41 students who had hematuria in the initial screening. Among 33 who complied the second test, only one student showed asymptomatic isolated hematuria and those remaining students were normal. Conclusion : 1) Because of high false positive hematuria rate in the urinary mass screening, it dosen't seem to be appropriate that hematuria screening using dipsticks be included in the urinary mass screening. 2) A unified organization is needed from the fret that so various results of urinary mass screening came out. 3) Positive rates of pyuria and nitrite were so low that validity of urinary mass screening for urinary tract infection needs more studies.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.41-44
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• 2016

We report here a case of maternal 3-methylcrotonyl-coenzyme A carboxylase (3-MCC) deficiency in a Korean woman. Her 2 infants had elevated 3-hydroxyisovalerylcarnitine (C5-OH) on a neonatal screening test by liquid chromatography-tandem mass spectrometry (LC-MS/MS), but normal results were found on urine organic acid analysis. The patient was subjected to serial testing and we confirmed a maternal 3-MCC deficiency by blood spot and breast milk spot test by LC-MS/MS, serum amino acid analysis, urine organic acid and molecular genetic analysis that found c.838G>T (p.Asp280Tyr) homozygous mutation within exon 9 of the MCCB gene. Especially, we confirmed marked higher levels of C5-OH on breast milk spot by LC-MS/MS, in the case of maternal 3-MCC deficiency vs. controls.

• Journal of Preventive Medicine and Public Health
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• v.28 no.3 s.51
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• pp.543-550
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• 1995

The authors conducted a cross-setional study to evaluate the differences of screening test results between clerks and laborers in an occupational health center in Taegu, 1992. A total of 10, 207 workers was included in the study. Of these, male were 6,597 and female 3,610. Constitutional variables included were items of health examination and some confounding variables(sex, age, body weight and work duration). All analyses were conducted separately for each sex through the use of multiple logistic regression analysis on occupation, controlling for age, work duration, and body weight. Laborers showed abnormal hearing test more often than clerks in both sexes. The blood pressure that showed statistical significance in univariate analysis in both sexes lost its significance after controlling covariates. Liver function and urine protein had statistically significant differences between two occupational groups in males and visual correction did in females. The results suggest that there are differences clerks and laborers in some of screening tests and analytic studies are needed to identify the causes of the differences.

• 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.

• Toxicological Research
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• v.25 no.2
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• pp.59-69
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• 2009

Metabolomics which deals with the biological metabolite profile produced in the body and its relation to disease state is a relatively recent research area for drug discovery and biological sciences including toxicology and pharmacology. Metabolomics, based on analytical method and multivariate analysis, has been considered a promising technology because of its advantage over other toxicogenomic and toxicoproteomic approaches. The application of metabolomics includes the development of biomarkers associated with the pathogenesis of various diseases, alternative toxicity tests, high-throughput screening (HTS), and risk assessment, allowing the simultaneous acquisition of multiple biochemical parameters in biological samples. The metabolic profile of urine, in particular, often shows changes in response to exposure to xenobiotics or disease-induced stress, because of the biological system's attempt to maintain homeostasis. In this review, we focus on the most recent advances and applications of metabolomics in toxicological research.

• Neonatal Medicine
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• v.25 no.2
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• pp.58-65
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• 2018

Purpose: The purpose of this study is to describe the rate of cytomegalovirus (CMV) virolactia, and the prevalence of breast milk (BM)-transmitted postnatal CMV infection among premature infants after freeze-thawing (FT) and Holder pasteurization (HP) of breast milk. Methods: This is a single-center, retrospective study of 312 infants born at less than 32 weeks of gestation, or with a birth weight less than 1,500 g from January 2013 to June 2017. All infants were screened for CMV-specific immunoglobulin (Ig) G and IgM at birth. Initial CMV specific polymerase chain reaction (PCR) and CMV culture were performed on mothers' BM and babies' urine within the first 21 days of life. FT and HP of BM was used to prevent the transmission of CMV. For the surveillance of postnatal CMV infection, CMV culture and CMV specific PCR of urine from babies were repeated one to two months after the initial screening. Screening for viremia and viruria was performed if postnatal CMV infection was suspected. Results: Among 178 BM samples obtained from mothers of CMV-IgG-seropositive infants, 80 (44.9%) were CMV PCR positive. CMV deoxyribonucleic acid (DNA) was detected in five of the 22 BM samples (22.7%) obtained from the mothers of CMV-IgG seronegative infants. When CMV DNA load in BM was measured before and after HP, various results were shown. Sixty-three infants out of 232 (27.2%) were evaluated for postnatal CMV infection and four infants out of 63 (6.3%) were infected. Conclusion: Interventions to prevent BM-transmitted CMV infection can reduce the chance of postnatal CMV infection, but not completely eliminate it.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.142-149
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• 2003

Purpose : The urinary mass screening program for the detection of urinary abnormalities in school aged population has been performed in Seoul since 1981. Nation-wide urinary mass screening program was also performed since 1998. The aim of this study was to analyze the cause and nature of isolated proteinuria detected by chance on the urinary mass screening test in Busan and Kyungsangnam-do Province Methods : The medical records of 44 cases of isolated proteinuria detected by chance on the urinary mass screening test in Busan and Kyungsangnam-do Province, and evaluated for urinary abnormalities at the pediatrics outpatients renal clinics of Busan Paik Hospital from April 2002 to August 2003 were reviewed prospectively. Results : The cause and incidence of isolated proteinuria were as follows; transient proteinuria 4 cases(9.1%), orthostatic proteinuria 36 cases(81.8%) and persistent proteinuria 4 cases (9.1%). The total protein amount of the 24 hour urine were $121.0{\pm}136.4\;mg$ in transient proteinuria, $179.1{\pm}130.0\;mg$ in orthostatic proteinuria and $1532.8{\pm}982.5\;mg$ in persistent proteinuria. In the orthostatic proteinuria group, the total protein amount of the 24 hour urine was in the range of 40-616 mg. Spot urine protein/creatinine ratio(PCR) were $0.10{\pm}0.01$ in transient proteinuria, $0.61{\pm}0.61$ in orthostatic proteinuria and $4.35{\pm}4.04$ in persistent proteinuria. In the orthostatic proteinuria group, spot me PCR was in the range of 0.09-2.32. Renal biopsy was peformed in 4 children of the persisitent proteinuria group. They showed minimal change in 1 case, membranoproliferatiye glomerulonephritis in 2 cases and secondary renal amyloidosis in 1 case. Conclusion : The majority of isolated proteinuria which was detected by chance on school urinary mass screening were transient or orthostatic proteinuria. Even though the incidence of persistent proteinuria was much lower, it is necessary to take care of these children regularly and continuously, because persistent proteinuria itself is a useful marker of the progressive renal problems.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.45-48
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• 2016

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive mitochondrial disorder of fatty acid ${\beta}$-oxidation, and is associated with mutations in the acyl-CoA dehydrogenase (ACADS) gene. Recent advances in spectrometric screening for inborn errors of metabolism have helped detect several metabolic disorders, including SCADD, without symptoms in the neonate period. This allows immediate initiation of treatment and monitoring, so they remain largely symptomless metabolic disease. Here, we report a 15-month-old asymptomatic male, who was diagnosed with SCADD by newborn screening. Spectrometric screening for inborn errors of metabolism 72 hours after birth revealed an elevated butyrylcarnitine (C4) concentration of $2.25{\mu}mol/L$ (normal, < $0.99{\mu}mol/L$). Urinary excretion of ethylmalonic acid was also elevated, as detected by urine organic acid analysis. To confirm the diagnosis of SCADD, direct sequencing analysis of 10 coding exons and the exon-intron boundaries of the ACADS gene were performed. Subsequent sequence analysis revealed compound heterozygous missense mutations c.164C>T (p.Pro55Leu) and c.1031A>G (p.Glu344Gly) on exons 2 and 9, respectively. The patient is now growing up, unretarded by symptoms such as seizure and developmental delay.

• Mass Spectrometry Letters
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• v.4 no.4
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• pp.59-66
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• 2013

A metabolomics study was conducted to identify urinary biomarkers for breast cancer, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), analyzed by principal components analysis (PCA) as well as a partial least squares-discriminant analysis (PLS-DA) for a metabolic pattern analysis. To find potential biomarkers, urine samples were collected from before- and after-mastectomy of breast cancer patients and healthy controls. Androgens, corticoids, estrogens, nucleosides, and polyols were quantitatively measured and urinary metabolic profiles were constructed through PCA and PLS-DA. The possible biomarkers were discriminated from quantified targeted metabolites with a metabolic pattern analysis and subsequent screening. We identified two biomarkers for breast cancer in urine, ${\beta}$-cortol and 5-methyl-2-deoxycytidine, which were categorized at significant levels in a student t-test (p-value < 0.05). The concentrations of these metabolites in breast cancer patients significantly increased relative to those of controls and patients after mastectomy. Biomarkers identified in this study were highly related to metabolites causing oxidative DNA damage in the endogenous metabolism. These biomarkers are not only useful for diagnostics and patient stratification but can be mapped on a biochemical chart to identify the corresponding enzyme for target identification via metabolomics.