• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.18-23
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• 2016

Objective: Newborn screening leads to improved treatment and disease outcomes, but false-positive newborn screening results may impact include parental stress and anxiety, perception of child as unhealthy, parent-child relationship dysfunction, and increased infant hospitalizations. The purpose of this study was to investigate of the false positive rates and the causative factors of false positive results in Tandem Mass Spectrometry (TMS) in single center. Methods: Records were reviewed for all 18,872 subjects who were born in Cheill General Hospital, during January 1st, 2012 to December 31st, 2014. 17,292 neonates (91.62%) were tested for tandem mass screening almost in 2-5th day of life. Newborn babies whose first results were abnormal had been tested repeatedly by same methods in 7-14 day. If the results were abnormal again, further evaluation was performed. TMS analysis included data for the 43 disorders screened for using TMS broken down into three categories: fatty acid oxidation disorders, organic acidurias, and aminoacidopathies. The impact of several factors on increased false positive rates was analyzed using a multivariate analysis: time from birth to sample collection, birth weight, birth height, BMI, gender, gestational age, delivery type. Results: Males of the subjects were 8942 (51.7%), female 8350 (48.3%), the mean gestational age was $38.6{\pm}1.7$ weeks, the average birth weight $3,155.6{\pm}502.4g$, the average birth height $49.1{\pm}2.9cm$, and the average BMI $13.0{\pm}3.8(kg/m^2)$. Vaginal delivery cases were 9713 (56.2%), caesarean section 7,579 (43.8%). The average date of the inspection was $2.8{\pm}1.1$ days. 224 cases were identified as TMS positive. All the subjects were false positive (222/17,292, 1.30%) except 2 cases (1 male; benign phenylketonuria and 1 female; Short chain acyl-CoA dehydrogenase deficiency). The false positive rates were 0.61% in fatty acid oxidation disorders, 0.25% in organic acidurias, and 0.45% in aminoacidopathies. In our study, the date of inspection got late, the false positive rates got higher. Because almost the cases of late test date were in treatment in neonatal intensive care unit so their test date was affected by their medical conditions. False positive rate was higher in extreme immaturity${\leq}27$ weeks than newborns of gestational age >27 weeks [OR=6.957 (CI=1.273-38.008), p<0.025] and extremely low birth weight<1,000 g than newborns of birthweight ${\geq}1,000g$ [OR=5.616 (CI=1.134-27.820), p<0.035]. Conclusion: False positive rate of TMS was 1.30% in Cheil General Hospital. Lower gestational age and birth weight impacted on increased false positive rates. Better understanding of factors that influence the reporting of screening tests, and the ability to modify these important factors, may improve the screening process and reduce the need for retesting. of screening tests, and the ability to modify these important factors, may improve the screening process and reduce the need for retesting.

• 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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.10 no.1
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• pp.47-50
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• 2010

• 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.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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.40-43
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• 2015

Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is an autosomal recessive mitochondrial disorder of fatty acid oxidation associated with mutations in the ACADS gene. While patients diagnosed clinically have a variable clinical presentation, patients diagnosed by newborn screening are largely asymptomatic. We describe here the case of a 1-year-old male patient who was detected by newborn screening and diagnosed as SCAD deficiency. Spectrometric screening for inborn errors of metabolism at 72hrs after birth showed elevated butyrylcarnitine (C4) level of 1.69 mol/L (normal, <0.83 mol/L), C4/C2 ration of 0.26 (normal, <0.09), C5DC+C60H level of 39 mol/L (normal, <0.28 mol/L), and C5DC/C8 ration of 7.36 (normal, <4.45). The follow-up testing at 18 days of age were performed: liquid chromatography tandem mass spectrometry (LC-MS/MS), urine organic acids, and quantitative acylcarnitine profile. C4 carnitine was elevated as 0.91; urine organic acid analysis showed elevated ethylmalonic acid as 62.87 nmol/molCr (normal, <6.5), methylsuccinate 6.81 nmol/molCr (normal, not detected). Sequence analysis of ACADS revealed a homozygous missense mutation, c.164C>T (p.Pro55Leu). He is growing well and no episodes of seizures or growth retardation had occurred.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.23 no.2
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• pp.39-44
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• 2023

Hereditary tyrosinemia type 1 (HT-1) is a metabolic disorder caused by biallelic pathogenic variants in the fumarylacetoacetate hydrolase (FAH) gene, which impairs the function of the FAH enzyme, resulting in the accumulation of tyrosine's toxic metabolites in hepatocytes and renal tubular cells. As a consequence, individuals with HT-1 exhibit symptomatic manifestations. Rapid diagnosis and treatment of HT-1 can prevent short-term death and long-term complications. A 15-day-old boy presented to the outpatient department with elevated levels of tyrosine on his newborn screening tests conducted at the age of 3 and 10 days, respectively. Further blood tests revealed increased levels of alpha-fetoprotein and amino acids including tyrosine and threonine. Urine organic acid tests indicated a significant elevation in tyrosine metabolites, as well as the presence of succinylacetone (SA), which led to the diagnosis of HT-1. Two pathogenic and likely pathogenic variants of FAH compatible with HT-1 were also detected. He began a tyrosine-restricted diet at one month old and received nitisinone (NTBC) at two months old. With continued treatment, the patient's initially elevated AFP level, detection of SA in the urine, and mild hepatomegaly showed improvement. During four years and seven months of treatment, there were no exceptional complications apart from an increase in tyrosine levels and a delay in speech. We report a case of tyrosinemia type 1 detected through newborn screening, treated with dietary restriction and NTBC, with a good prognosis.

• Journal of Yeungnam Medical Science
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• v.30 no.1
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• pp.21-24
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• 2013

Hemolytic disease in a newborn that causes early jaundice is common. It is often due to the Rh (D) and ABO incompatibility, but rarely due to unexpected antibodies. Among these unexpected antibodies, the anti-$Di^a$Dia antibody rarely occurs. The anti-$Di^a$ antibody was observed in the serum and red-cell eluate of an infant, and in the serum of his mother. The frequency of the appearance of the $Di^a$ antigen in the Korean population is estimated to be 6.4-14.5%. This paper reports a case of hemolytic disease in a newborn associated with the anti-$Di^a$ antibody. A full-term male infant was transferred to the authors' hospital due to hyperbilirubinemia the day after his birth. The laboratory data indicated a hemoglobin value of 11.6 g/dL, a reticulocyte count of 10.6%, a total bilirubin count of 14.4 mg/dL, a direct bilirubin count of 0.6 mg/dL, and a positive result in the direct Coombs' test. Due to the identification of an irregular antibody from the maternal serum, an anti-$Di^a$ antibody was detected, which was also found in the eluate made from the infant's blood. The infant had been treated with phototherapy and intravenous immunoglobulin since the second day after his birth and was discharged due to an improved condition without exchange transfusion. Therefore, in cases of iso-immune hemolytic disease in a newborn within 24 hours from birth who had a negative result in an antibody screening test, the conduct of an anti-$Di^a$ antibody identification test is recommended due to the suspicion of an anti-$Di^a$ antigen, followed by early administration of intravenous immunoglobulin.

• 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.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.14-20
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• 2018

Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic disorders caused by specific lysosomal enzyme deficiencies leading to the sequential degradation of glycosaminoglycans, causing substrate accumulation in various cells and tissues and progressive multiple organ dysfunction. The rare disease medical care team at Mackay Memorial Hospital in Taiwan has been dedicated to the study of MPSs for more than 20 years. Since 1999, more than 50 academic papers focusing on MPSs have been published in international medical journals. Topics of research include the following items regarding MPSs: incidence, natural history, clinical manifestations, gene mutation characteristics, cardiac function, bone mineral density, sleep studies, pulmonary function tests, hearing assessments, percutaneous endoscopic gastrostomy, anesthetic experience, imaging analysis, special biochemical tests, laboratory diagnostics, global expert consensus conferences, prenatal diagnosis, new drug clinical trials, newborn screening, and treatment outcomes. Of these published academic research papers, more than half were cross-domain, cross-industry, and international studies with results in cooperation with experts from European, American and other Asian countries. A cross-specialty collaboration platform was established based on high-risk population screening criteria with the acronym "BECARE" (Bone and joints, Eyes, Cardiac and central nervous system, Abdomen and appearance, Respiratory system, and Ear, nose, and throat involvement). Through this platform, orthopedic surgeons, rheumatologists, ophthalmologists, cardiologists, rehabilitation physicians, gastroenterologists, otorhinolaryngologists, and medical geneticists have been educated with regards to awareness of suspected cases of MPSs patients to allow for a further confirmative diagnosis of MPSs. Because of the progressive nature of the disease, an early diagnosis and early multidisciplinary therapeutic interventions including surgery, rehabilitation programs, symptom-based treatments, hematopoietic stem cell transplantation, and enzyme replacement therapy, are very important.