• 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.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.

• The Journal of the Korean life insurance medical association
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• v.18
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• pp.107-110
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• 1999

The disorders of congenital metabolic errors causing mental retardation can be prevented by early diagnosis and treatment. We analysed 144,000 neonatal blood samples for phenyketonuria(PKU), maple syrup urine disease(MSUD), homocystinuria(HCU) and histidinuria(HE) by bacterial inhibition method, and galactosemia(GAL) by Paigen method. In our survey, the positive were 4 samples in PKU(4mg/dl;2, 6mg/dl;1, 8mg/dl;1), 8 samples in MSUD(4mg/dl;2, 6mg/dl;2, 8mg/dl;3, 10mg/dl;1), 4 samples in HCU(4mg/dl;2, 6mg/dl;2), 4 samples in Galactosemia(4mg/dl;2, 6mg/dl;1, 8mg/dl;1), respectively. while, no one was positive in HE. The frequncy rate were 1/36,000 for PKU, HCU and GAL, 1/18,000 for MSUD, respectively. But those for HE couldn't be detected in our survey. In this study, the hightest frequency rate was 1/18,000 of MSUD, following were 1/36,000 for PKU, HCU and GAL, respectively. As results our data, it is our opinion that neonatal screening should be performed in terms of national policies for ealy diagnosis and theraphy.

• Clinical and Experimental Pediatrics
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• v.54 no.10
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• pp.425-428
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• 2011

Ornithine transcarbamylase (OTC) deficiency is well known as the most common inherited disorder of the urea cycle, and 1 of the most common causes of hyperammonemia in newborns. We experienced a case of a 3-day-old boy with OTC deficiency who appeared healthy in the first 2 days of life but developed lethargy and seizure soon afterwards. His serum ammonia level was measured as > $1,700{\mu}g/dL$ (range, 0 to $45{\mu}g/dL$). Continuous renal replacement therapy (CRRT) in the mode of continuous venovenous hemodiafiltration was immediately applied to correct the raised ammonia level. No seizure occurred after the elevated ammonia level was reduced. Therefore, CRRT should be included as 1 of the treatment modalities for newborns with inborn errors of metabolism, especially hyperammonemia. Here, we report 1 case of successful treatment of hyperammonemia by CRRT in a neonate with OTC deficiency.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.174-177
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• 2014

Isolated methylmalonic acidemia (MMA) is a group of autosomal recessive inborn errors of metabolism caused by impaired activity of methylmalonyl-coenzyme A mutase (MCM). Mutations in the gene encoding MCM (MUT ) is the most common cause of isolated MMA. In this report, we identify an asymptomatic 15 days old female who had elevated C3-acylcarnitine (C3) in the newborn screening. Her serum homocysteine was normal and urine methylmalonic acid was increased that suggested isolated MMA. She was maintained on a low-protein diet and carnitine supplementation. At 3 months of age, she was still asymptomatic and had normal growth. We analyzed MUT gene mutations. Two heterozygote mutations in the MUT gene were identified including c.323G>A and c.1672+2T>C (IVS8(+2)T>C. Among these, c.1672+2T>C (IVS8(+2)T>C) have not been described previously.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.2
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• pp.94-98
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• 2012

Purpose: Developmental delay and mental retardation are frequently occurring disorders that present major socio-economic burden on the affected individual's family and society. Both can be congenital or acquired. However, a large number of people are institutionalized without exact diagnosis and, as a result, have not received proper care. Methods: 508 subjects with mental retardation or developmental delay from six institutions in Chung Buk Province were clinically evaluated and screened for metabolic and endocrinologic problems between 2000 and 2012. Results: Clinical genetic disorders were observed in 52 (10.2%) subjects. Cerebral palsy attributed to 21% of the institutionalized. 18 (3.5%) were diagnosed with metabolic disorders and 13 (2.6%) exhibited secondary endocrinologic dysfunction. Over 16% showed metabolic evidence of malnutrition. Conclusion: 21% and 3.5% of the population institutionalized due to mental retardation or developmental delay were afflicted by preventable cerebral palsy and metabolic disorders, respectively. Through early identification of the causes and early treatment, it may be possible to prevent, reduce, or alleviate the disability of many institutionalized individuals. Further research is imperative for establishing guidelines for diagnostic investigation for mental retardation.

• 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 The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.35-42
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• 2018

Purpose: To follow up Korean patients with metabolic and endocrine disorders ascertained by Korea Genetics Research Center, and assess the long-term effectiveness of extended newborn screening program in Korea. Methods: From January 2000 to December 2017, tandem mass spectrometry and fluoroimmunoassay were employed in extended newborn screening (NBS). The NBS program obtained dried blood spots from 283,626 babies, 48 hours after birth, and screened for galactosemia, congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), and 50 preventable inborn errors of amino acid, fatty acid, and organic acid metabolism. Results: 28 cases of amino acid disorders, 75 cases of organic acid disorders, 27 cases of fatty acid disorders, 51 cases of urea cycle disorders, 127 cases of CH, 14 cases of CAH, and 15 cases of galactosemia were ascertained through NBS and subsequent confirmatory laboratory tests. Patients with amino acid metabolic disorders, galactosemia, CH, or CAH were more likely to have a better long-term outcome if detected early. Early management of MSUD led to much better outcome in over 90%. Despite early intervention, 32% of other organic acidemia cases still resulted in developmental delay and neurological problems. Fatty acid disorders showed varied results; those with EMA and MCAD had a good outcome, but those with VLCAD had serious neurological problems and considerably higher mortality. 75% with UCD experienced serious neurological complications and higher mortality. Conclusion: The nation-wide NBS program must be accompanied by comprehensive long-term management and physician and family education of inborn errors of metabolism for a better outcome.

• Korean Journal of Clinical Laboratory Science
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• v.48 no.2
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• pp.68-73
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• 2016

Ammonia is very toxic, and causes neuronal damage via excitotoxicity, oxidative stress, and inflammation. Because the liver is the primary organ for ammonia metabolism, compromised liver function can result from inborn errors of metabolism. Measurement of blood ammonia has some limitations. Recently, several laboratories examined possible concurrent increases in plasma ammonia. However, the collection, handling, storage, and analysis of blood samples are all potential sources of error. For evaluation of rapidity and reliability of measurement of blood ammonia, the DRI-CHEM 100 (Fuji Film Co., Japan) and COBAS 8000 (Roche Diagnostic Ltd., Switzerland) analyzer were used for analysis of ammonia level values. The results of this study detected a high correlation between analyzer. Therefore, one-step measurement was suitable for ammonia analysis. After sampling of the ammonia in the time slot for measurement an increase to 46.5, 57.4, and 79.0 (${\mu}g/dL$) was observed at 30, 90, and 180 minutes. In addition, specific capacity of the ammonia, 7, 10, and 13 (${\mu}L$), was measured as 39, 46, and 43 (${\mu}g/dL$), respectively, and the FDC-100 analyzer was more effective in $10{\mu}L$ (p<0.001). In conclusion, the evaluated analysis may offer useful information for clinical application.

• 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.