• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.1-7
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• 2023

Inherited metabolic disorders (IMD) are a group of disorders involving various metabolic pathways. Genetic diagnosis of IMD has been challenging because of extremely heterogeneous nature and extensive laboratory and/or phenotype overlap. Conventional genetic diagnosis was a gene-by-gene approach that needs a priori information on the causative genes that might underlie the IMD. Recent implementation of next-generation sequencing (NGS) technologies has changed the process of genetic diagnosis from a gene-by-gene approach to simultaneous analysis of targeted genes possibly associated with the IMD using gene panels or using whole exome/genome sequencing (WES/WGS) covering entire human genes. Clinical NGS tests can be a cost-effective approach for the rapid diagnosis of IMD with genetic heterogeneity and are becoming standard diagnostic procedures.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.2
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• pp.65-71
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• 2015

Since the secretion of specific chiral isomers in urine (or plasma) is very crucial to diagnose some inborn metabolic disorders, clinical application of dual column achiral differential method has been performed for the absolute configuration of chiral compounds. Extracted from the acidified urine with diethyl ether, carboxylic functional group of organic acid (stereoisomers of the volatile) was derivatized with (-)-menthylation or (S)-(+)-3-methyl-2-butylation and followed by O-trifluoroacylation. Each of the enantiomers was accurately separated from the library matched double column (achiral) with a retention index (I). In various inborn metabolic disease urines, absolute chirality was identified correctly in the urine (10 patients) with inborn metabolic disease (including secretion of D, L- lactic acid, D, L-3-hydroxybutyric acid, and D, L-2-hydroxyglutaric acid). In this study, we identified and isolated the volatile diastereomer as a useful diagnostic marker, this successful application to urine specimens may be useful for diagnostic classification of inherited metabolic disorders.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.4 no.1
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• pp.61-63
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• 2004

• 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.17 no.2
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• pp.39-47
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• 2017

Purpose: A sensitive gas chromatography mass spectrometry (GC-MS) method was developed for screening of fatty acid oxidation disorders. Methods: The assay utilized a simple protein precipitation with sulfosalicylic acid followed by tert-butyl dimethylsilyl (TBDMS) derivatization of hydroxyl functional group by N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA). Results: Calibration curves of spiked pooled plasma showed a linear relationship in the range of 0.01 ng -2 mg with correlation coefficient value greater than 0.98. Limits of detection (LOD) and limits of quantification (LOQ) were found in the range of 0.9-8.8 ng and 9-88 ng, respectively. Conclusion: The new developed method might be useful for a rapid, sensitive screening of inherited fatty acid oxidation disorders. In addition, the method expected to be one of the alternative method for screening newborns of metabolic disorders in the laboratories where expensive MS/MS is unavailable.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.108-115
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• 2005

Inherited metabolic diseases (IMD) comprise a large class of genetic diseases involving disorders of metabolism. The majorities are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others. Because of the multiplicity of conditions, many different diagnostic tests are used for screening of IMD. Molecular genetic diagnosis is the detection of pathogenic mutations in DNA and/or RNA samples and is becoming a much more common practice in medicine today. The purpose of molecular genetic testing in IMD includes diagnostic testing, pre-symptomatic testing, carrier screening, prenatal diagnosis, preimplantation testing, and population screening. However, because of the complexity, difficulty in interpreting the result, and the ethical considerations, an understanding of technical, conceptual, and practical aspects of molecular genetic diagnosis is mandatory.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.23-26
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• 2005

• Journal of The Korean Society of Inherited Metabolic disease
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• v.24 no.1
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• pp.10-16
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• 2024

Congenital Disorders of Glycosylation (CDG) represent a complex group of inherited metabolic disorders resulting from defects in multiple pathways of glycosylation, a critical biochemical process for protein functionality and cellular communication. This review provides a comprehensive overview of CDG, including its history, epidemiology, classification, diagnostic complexities, and therapeutic developments. Despite advancements in understanding CDG and identifying over 160 subtypes, challenges remain due to the diverse clinical manifestations and multi-systemic involvement. Targeted therapy is available for only a few CDGs, but promising treatments are being investigated. Ongoing research is vital to developing targeted treatments and improving patient outcomes.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.10-18
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• 2014

Recent advances in the diagnosis and treatment of inborn errors of metabolism have improved substantially the prognosis of many of these diseases, if diagnosed early enough before irreversible damage occurs. This makes it essential that the practicing pediatrician, especially neonatologists be familliar with the clinical presentations and systematic approaches of these disorders. Characteristic clinical presentations, methods of systematic approach and typing of various disorders is discussed in this review. The signs of neurological dysfunctions of many IEMs manifesting in the neonatal period is very nonspecific, such as poor feeding, poor sucking, apnea or tachypnea, vomiting, hypertonia, hypotonia, seizure, letharginess, consciousness change and coma. Many other non-metabolic severe disorders of neonatal period such as neonatal sepsis and intracerebral hemorrhage share these nonspecific symptoms. Hyperammonemia, metabolic acidosis, ketosis and hyperlatic acidemia are observed in many of these conditions but there are exceptions in which conditions all basal laboratory tests are normal, such as NKH, sulfite oxidase deficiency and peroxisomal disorders. According to the results of basal laboratory tests, IEMs in the neonatal period can be categorized in to 6 types. Grouping of IEMs into 6 types will make confirmatory tests and early emergency treatment more efficient.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.1
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• pp.1-8
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• 2022

Long-chain fatty acid oxidation disorders (LC-FAOD) are an autosomal recessive inherited rare disease group that result in an acute metabolic crisis and chronic energy deficiency owing to the deficiency in an enzyme that converts long-chain fatty acids into energy. LC-FAOD includes carnitine palmitoyltransferase type 1 (CPT1), carnitine-acylcarnitine translocase (CACT), carnitine palmitoyltransferase type 2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), and trifunctional protein (TFP) deficiencies. Common symptoms of LC-FAOD are hypoketotic hypoglycemia, cardiomyopathy, and myopathy. Depending on symptom onset, the disease can be divided as neonatal period, late infancy and early childhood, adolescence, or adult onset, but symptoms can appear at any time. The neonatal screening test (NBS) can be used to identify the characteristic plasma acylcarnitine profiles for each disease and confirmed by deficient enzyme analysis or molecular testing. Before introduction of NBS, the mortality rate of LC-FAOD was very high. With NBS implementation as routine neonatal care, the mortality rate was dramatically decreased, but severe symptoms such as rhabdomyolysis recur frequently and affect the quality of life. Triheptanoin (Dojolvi^®), the first drug for pediatric and adult patients with molecularly confirmed LC-FAOD, has recently been approved by the US Food and Drug Administration in 2020. In this review, the diagnosis of LC-FAOD and treatment including triheptanoin are summarized.