• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.2
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• pp.46-52
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• 2022

Inborn errors of metabolism (IEM) are very rare and genetically transmitted diseases and have man y different symptoms related with multisystemic involvement. More rarely, endocrinopathies can be an early and first symptom of IEM, but presents with signs of later complications in adolescent or adulthood. The mechanisms of endocrine dysfunction in IEM are poorly understood. Hypogonadotropic hypogonadism is common in hemochromatosis, adrenoleukodystrophy, galactosemia, and glycogen storage disease. Many girls with classic galactosemia are at high risk for premature ovarian insufficiency (POI), despite an early diagnosis and good control. Mitochondrial diseases are multisystem disorders and are characterized by hypo- and hypergonadotrophic hypogonadism, thyroid dysfunction and insulin dysregulation. Glycogen storage disorders (GSDs), especially type Ia, Ib, III, V are assocciated with frequent hypoglycemic events. IEM is a growing field and is not yet well recognized despite its consequences for growth, bone metabolism and fertility. For this reason, clinicians should be aware of these diagnoses and potential endocrine dysfunction.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.21 no.1
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• pp.1-6
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• 2021

Among the various etiologies of cardiomyopathy, inborn errors of metabolism (IEM) is one of the underlying causes, especially in the pediatric population. The accurate identification of the IEM of cardiomyopathy may lead to better prognosis through disease-specific management. Therefore, clinicians should always keep in mind the possibility that IEM may be one of the underlying etiologies of cardiomyopathy, and carry out multi-systematic clinical approach to diagnosis of IEM. This review covers the pathophysiology, clinical presentations, typical laboratory findings, diagnosis, and proper treatment of each type of IEM-induced cardiomyopathy in pediatric patients to gain a deeper understanding of this subject.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.6
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• pp.518-527
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• 2021

Purpose: The incidence of hepatic steatosis among children has been increasing; however, data distinguishing simple steatosis from a more complex disorder are lacking. Methods: This study identified the etiologies resulting in hepatic steatosis through a retrospective review of pediatric liver biopsies performed in the last 10 years. A total of 158 patients with hepatic steatosis proven by histopathological evaluation were enrolled in the study, and baseline demographic features, anthropometric measurements, physical examination findings, laboratory data, ultrasonographic findings, and liver histopathologies were noted. Results: The two most common diagnoses were inborn errors of metabolism (IEM) (52.5%) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) (29.7%). The three most common diseases in the IEM group were glycogen storage disorders, Wilson's disease, and mitochondrial disease. The rates of consanguineous marriage (75.6%; odds ratio [OR], 26.040) and positive family history (26.5%; OR, 8.115) were significantly higher (p=0.002, p<0.001, respectively) in the IEM group than those in the NAFLD/NASH group. Younger age (p=0.001), normal anthropometric measurements (p=0.03), increased aspartate aminotransferase levels (p<0.001), triglyceride levels (p=0.001), and cholestatic biochemical parameters with disrupted liver function tests, as well as severe liver destruction of hepatic architecture, cholestasis, fibrosis, and nodule formation, were also common in the IEM group. Conclusion: Parents with consanguinity and positive family history, together with clinical and biochemical findings, may provide a high index of suspicion for IEM to distinguish primary steatosis from the consequence of a more complex disorder.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.123-134
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• 2014

Recent advances in the diagnosis and treatment of inborn errors of metabolism (IEM) have improved substantially the prognosis of many of these diseases, if diagnosed early enough before irreversible damage occurs. Diseases of inborn errors of metabolism are so diverse over several hundred disease up to now and may be several thousand in near future, and these diversities of IEMs make clinicians embarassed. 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. But after neonatal period, the signs of neurological deficits become specific and localized. The results of routine basal laboratory tests such as metabolic acidosis, hyperammonemia, lactic acidemia, ketonemia or hyperuricemia can give very important clinical clues for the diagnosis of IEMs. Even no abnormal findings on routine laboratory test could be very important clue for NKH, sulfite oxidase deficiency and peroxisomal disorders. These various clinical manifestations of these diverse diseases can be categorized and summarized. This makes it essential that the practicing clinicians be familiar with the clinical presentations and symptomatic and systematic approaches of these disorders. Characteristic clinical presentations, methods of symptomatic and systematic approach and typing of various disorders is discussed in this review.

• 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 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.

• 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.