• Clinical and Experimental Pediatrics
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• v.54 no.5
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• pp.183-191
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• 2011

Although antenatal diagnostic technique has considerably improved, precise detection and proper management of the neonate with congenital heart disease (CHD) is always a great concern to pediatricians. Congenital cardiac malformations vary from benign to serious conditions such as complete transposition of the great arteries (TGA), critical pulmonary and aortic valvular stenosis/atresia, hypoplastic left heart syndrome (HLHS), obstructed total anomalous pulmonary venous return (TAPVR), which the baby needs immediate diagnosis and management for survival. Unfortunately, these life threatening heart diseases may not have obvious evidence early after birth, most of the clinical and physical findings are nonspecific and vague, which makes the diagnosis difficult. High index of suspicion and astute acumen are essential to decision making. When patent ductus arteriosus (PDA) is opened Widely, many serious malformations may not be noticed easily in the early life, but would progress as severe acidosis/shock/cyanosis or even death as PDA constricts after few hours to days. Ductus dependent congenital cardiac lesions can be divided into the ductus dependent systemic or pulmonary disease, but physiologically quite different from each other and treatment strategy has to be tailored to the clinical status and cardiac malformations. Inevitably early presentation is often regarded as a medical emergency. Differential diagnosis with inborn error metabolic disorders, neonatal sepsis, persistent pulmonary hypertension of the newborn (PPHN) and other pulmonary conditions are necessary. Urgent identification of the newborn at such high risk requires timely referral to a pediatric cardiologist, and timely intervention is the key in reducing mortality and morbidity. This following review deals with the clinical presentations, investigative modalities and approach to management of congenital cardiac malformations presenting in the early life.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.42-46
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• 2016

Isovaleric acidemia is autosomal-recessively inherited and an inborn error of metabolism caused by abnormal leucine metabolism due to the genetic defect of IVD (Isovaleryl-CoA dehydrogenase). IVD corresponds to mitochondrial matrix enzyme that acts on converting isovaleryl-CoA into 3-methylcrotonyl-CoA in the leucine catabolism. The IVD gene is located at Chromosome 15q14-q15, particularly between base pair 40,405,485 and base pair 40,435,948. It consists of 12 exons and has been reported to cause over 50 diseases so far. We conducted IVD gene test on the patient with acute isovaleric acidemia and confirmed a new type of mutation for the first time. As a result of analyzing the IVD gene sequence, we found out that c.129T>G(p.Asn43Lys) and c.1033A>G(p.Asn345Asp) mutations exist as heterozygosity at Exon 1 and Exon 10 respectively, novel mutation.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.7-10
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• 2018

Rare diseases are life threatening or chronically debilitating diseases with a low prevalence (less than 2,000 people in a population), which includes lysosomal storage diseases. These diseases are often seen as unimportant especially in developing countries, such as Indonesia, due to small number of patients. National Rare Disease Center in Indonesia was pioneered almost 20 years ago and officially established in 2017 by the Indonesian Minister of Health. Lysosomal storage disease become the most commonly found inborn errors of metabolism (IEM) in Indonesia due to easily accessible diagnostic facilities. Currently there are 7 patients receiving ERT in this mixed-donation scheme, one patient with Gaucher disease and 6 patients with MPS type II. Few challenges for ERT in Indonesia include importation through special access scheme, preparation of ERT infusion in intensive care settting, and cost of treatment. Even with limited resources, healthcare professionals in Indonesia have been giving the best care possible for rare disease patients, especially to provide diagnostic facilities through collaboration and treatment options for treatable rare diseases. Improvements in care for rare disease patients are still needed.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.235-238
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• 2010

Fabry disease is a rare, X-linked inborn error of glycosphingolipid catabolism caused by a mutation in the gene encoding the ${\alpha}-galactosidase$ A (GLA) enzyme. We report two cases of Fabry disease in a 12-year-old boy who had acroparesthesia and in his elder brother with milder symptoms who were diagnosed by GLA activity assays and the presence of the GLA gene mutation.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.1
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• pp.48-53
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• 2014

Smith-Lemli-Opitz syndrome (SLO) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. Here, we describe Korean siblings with SLO who were diagnosed recently, and performed a review of literature about Korean cases with SLO to date. Microcephaly and syndactyly of the second and third toes are the most common physical finding in SLOS patients. Other malformations including growth failure, cleft palate or bifid uvula, various heart malformation, genital ambiguity in males are also accompanied. Not all patients showed low levels of serum cholesterol, so DHCR7 mutation analysis can be helpful to confirmative diagnosis. Two mutations on p.R352 locus (p.R352W and p.R352Q) are commonly identified in Korean SLO patients. Although rare in Korea, SLO should be considered in the differential diagnosis of growth failure with intellectual disability, especially in patients with multiple congenital anomalies.

• 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.13 no.1
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• pp.1-19
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• 2013

Inherited metabolic disorders are individually rare but as a whole, they are nor rare. Since Archibald Garrod introduced a concept of "inborn error of metabolism" or "chemical individuality", more than 600 diseases are currently known, affecting approximately one in 500 newborns cumulatively. They frequently manifest with acute, life-threatening crisis that requires immediate specific intervention or they present with insidious diverse symptoms and signs involving multiple visceral organs or tissues as well as central nervous system, hampering a correct diagnosis. In addition, many pediatricians are not familiar with all diagnostic and therapeutic strategies for diverse inherited metabolic disorders. However, the prognosis of affected children are heavily dependent on rapid and effective treatment. In this lecture, practical guidelines for the specific diagnosis based on diverse clinical features of inherited metabolic disorders will be described. Many sophisticated laboratory tests are available for the confirmatory diagnosis of each disease, which is challenging to general pediatricians with respect to knowledge about biochemical metabolite assay test, enzymatic test and DNA diagnostic tests. Sample collections, indications, methods and interpretation of results in varying laboratory tests will be listed as well.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.7-11
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• 2002

Isovaleric acidemia is an inborn error in metabolism due to a defect in isovaleryl-CoA dehydrogenase. Accumulation of serum isovaleric acid causes poor feeding, vomiting, lethargy, hypothermia, convulsion, mental retardation, etc. It is inherited as an autosomal recessive trait. Since the first reports of isovaleric acidemia by Tanaka et al in 1966, more than 60 cases have been reported. There are two clinically different presentations of isovaleric acidemia, with about half the patients presenting with an acute severe neonatal form and about half with a chronic intermittent form. The difference in clinical presentation may not be a consequence of differing severities of the causative mutation, but a result of the timing of application of catabolic stress or the ability to form isovalerylglycine. We described here clinical and organic acid analytical findings of in 3 cases isovaleric acidemia.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.5 no.1
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• pp.76-87
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• 2005

Various disorders cause hyperammonemia during childhood. Amongthem are those caused by inherited defects in urea synthesis and related metabolic pathways. These disorders can be grouped into two types: disorders of the enzymes that comprise the urea cycle, and disorders of the transporters or metabolites of theamino acids related to the urea cycle. Principal clinical features of these disorders are caused by elevated levels of blood ammonium. Additional disease-specific symptoms are related to the particular metabolic defect. These specific clinical manifestations are often due to an excess or lack of specific amino acids. Treatment of urea cycle disorders and related metabolic diseases consists of nutritional restriction of proteins, administration of specific amino acids, and use of alternative pathways for discarding excess nitrogen. Although combinations of these treatments are extensively employed, the prognosis of severe cases remains unsatisfactory. Liver transplantation is one alternative for which a better prognosis is reported.

• YAKHAK HOEJI
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• v.55 no.1
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• pp.56-63
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• 2011

Fabry disease (FD) is an X-linked inborn error of glycoshpingolipid metabolism resulting from mutation in the enzyme ${\alpha}$-galactosidase A gene. The disease is an X-linked lipid storage disorder and the lack of ${\alpha}$-Gal A causes an intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb-3). Measurement of Gb-3 in plasma has clinical importance for monitoring after enzyme replacement therapy for confirmed FD patients. Using electrospray ionization MS/MS we had developed, a simple, rapid, and highly sensitive analytical method for Gb-3 in plasma was used for the purpose of screening FD among high risk groups in Korean population. To date, no comprehensive results for FD screening have been performed and reported in Korea. We screened 1,100 outpatients from 13 hospitals (including clinics) to assess the incidence of FD among patients in high risk groups. For patients with borderline level amount of Gb-3, we repeated Gb-3 or performing complementary or confirmative assay with ${\alpha}$-Gal A activity and DNA mutaion analysis for confirmation diagnosis. Of 1,100 we diagnosed 3 FD with 2 classical type and 1 carrier (0.27%).