• Journal of Genetic Medicine
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• v.10 no.2
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• pp.81-87
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• 2013

Pseudohypoaldosteronism (PHA), a rare syndrome of systemic or renal mineralocorticoid resistance, is clinically characterized by hyperkalemia, metabolic acidosis, and elevated plasma aldosterone levels with either renal salt wasting or hypertension. PHA is a heterogeneous disorder both clinically and genetically and can be divided into three subgroups; PHA type 1 (PHA1), type 2 (PHA2) and type 3 (PHA3). PHA1 and PHA2 are genetic disorders, and PHA3 is a secondary disease of transient mineralocorticoid resistance mostly associated with urinary tract infections and obstructive uropathies. PHA1 includes two different forms with different severity of the disease and phenotype: a systemic type of disease with autosomal recessive inheritance (caused by mutations of the amiloride-sensitive epithelial sodium channel, ENaC) and a renal form with autosomal dominant inheritance (caused by mutations of the mineralocorticoid receptor, MR). In the kidneys, the distal nephron takes charge of the fine regulation of water absorption and ion handling under the control of aldosterone. Two major intracellular actors necessary for the action of aldosterone are the MR and the ENaC. Impairment of the intracellular aldosterone signal transduction pathway results in resistance to the action of mineralocorticoids, which leads to PHA. Herein, ion handling the distal nephron and the clinico-genetic findings of PHA are reviewed with special emphasis on PHA type 1.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.42-48
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• 2012

Pompe disease is a rare lysosomal glycogen storage disorder caused by a total or partial deficiency of the acid ${\alpha}$-glucosidase (GAA) enzyme due to the GAA gene mutations. The classic infantile form of Pompe disease is a rapidly progressive multi-organ disease with hypotonia, generalized muscle weakness, and hypertrophic cardiomyopathy, usually leading to death in the first 2 years of life. Enzyme replacement therapy with recombinant human GAA has been shown to be effective and subsequently yielded promising results. Here, we present clinical and genetic characteristics of three Korean non-classic infantile Pompe patients, and the short term efficacy of enzyme replacement therapy. Considering that enzyme replacement therapy can change the natural course of infantile Pompe disease, early diagnosis and early initiation of treatment is critical to improving patient outcomes.

• Clinics in Shoulder and Elbow
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• v.12 no.1
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• pp.84-88
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• 2009

Purpose: Calcium pyrophosphate dihydrate crystal deposition disease(CPPD) is a disease of the elderly and extremely rare in young individuals. If young people develop CPPD crystal deposition disease, it may be associated with metabolic diseases, such as hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's disease, hypothyroidism, and gout. Materials and Methods: Therefore, in young-onset CPPD crystal deposition disease, an investigation of any predisposing metabolic conditions is warranted. Conclusion: We report a case of a young female patient who presented with idiopathic CPPD crystal deposition disease at 25 years of age.

• Clinical and Experimental Pediatrics
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• v.57 no.7
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• pp.329-332
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• 2014

3-methylcrotonyl-coenzyme A carboxylase (3MCC) deficiency is an autosomal recessive disorder in which leucine catabolism is hampered, leading to increased urinary excretion of 3-methylcrotonylglycine. In addition, 3-hydroxyisovalerylcarnitine levels increase in the blood, and the elevated levels form the basis of neonatal screening. 3MCC deficiency symptoms are variable, ranging from neonatal onset with severe neurological abnormality to a normal, asymptomatic phenotype. Although 3MCC deficiency was previously considered to be rare, it has been found to be one of the most common metabolic disorders in newborns after the neonatal screening test using tandem mass spectrometry was introduced. Additionally, asymptomatic 3MCC deficient mothers have been identified due to abnormal results of unaffected baby's neonatal screening test. Some of the 3MCC-deficient mothers show symptoms such as fatigue, myopathy, or metabolic crisis with febrile illnesses. In the current study, we identified an asymptomatic 3MCC deficient mother when she showed abnormal results during a neonatal screening test of a healthy infant.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.1
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• pp.14-23
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• 2020

Classic galactosemia is a rare genetic disorder in Korea and the mutation spectrum in Koreans differs from that of Caucasians and non-Caucasian Americans. Classic galactosemia is considered a metabolic complication that is preventable by early detection via newborn screening and dietary treatment. In this most recent case of Korean galactosemia, the patient showed early initiation of clinical symptoms, which manifested during the neonatal period. The patient achieved normalization via diet management to correct metabolic complications. In addition, we assessed the characteristics of mutations in 25 Korean galactosemia cases via a literature review of studies associated with classic galactosemia.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.2
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• pp.104-107
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• 2012

Alpha-methylacetoacetic aciduria is a rare inborn metabolic disorder, caused by acetyl-CoA acetyltransferase-1 deficiency. This enzyme acts on the last step of isoleucine metabolism. It dissociates 2-Methyl-3-Hydroxybutyryl-CoA into propionyl-CoA and acetyl-CoA. ACAT1 is the causative gene. Most patients manifest recurrent ketotic metabolic acidosis, but some patients can be identified in their presymptomatic period by newborn screening. Urinary organic acid profile is characterized by increased amounts of 2-Methyl-3-Hydroxybutyric acid, tiglylglycine, and 2-methyl acetoacetic acid. In this report, a Korean patient with alpha-methylacetoacetic aciduria is described. This is the first Korean case report confirmed by genetic testing.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.3
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• pp.77-84
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• 2017

Purpose: From the early 1990's, use of Tandem mass spectrometry in neonatal screening test, made early stage detection of disorders that was not detectable by the previous methods of inspection. This research aims to evaluate the frequency of positive results in national neonatal screening test by Tandem mass spectrometry and its usefulness. Methods: A designated organization for inherited metabolic disorder executed neonatal screening test on newborns using Tandem mass spectrometry from January 2006 to December 2015, followed by the investigation of these data by the Planned Population Federation of Korea (PPFK), and this research analyzed those inspected data from the PPFK. Results: Among total childbirth of 4,590,606, from January 2006 to December 2015, 3,445,238 were selected for MS/MS and conduction rate was 75.1%. 261 out of the selected 3,445,238 were confirmed patients and for last decade, detection rate of total metabolic disorder was 1/13,205. In 261 confirmed patients, 120 had an amino acid metabolic disorder and its detection rate was 1/28,710 and 110 had an organic acid metabolic disorder and detection rate was 1/31,320. Also, 31 had a fatty acid metabolic disorder and detection rate was 1/13,205. Conclusion: Inherited metabolic disorder is very rare. Until now, it was difficult to precisely grasp an understanding on the national incidence of inherited metabolic disorder, due to lack of overall data and inconsistent and incomplete long-term result analysis. However, this research attempted to comprehensively approach the domestic incidence, by analyzing previous 10 years of data.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.9-17
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• 2015

Glycogen storage disease (GSD) type Ia is rare inborn metabolic disorder, caused by glucose-6-phosphatase deficiency. It characterized by hepatomegaly, hypoglycemia, lactic acidosis, hypertriglyceridemia, and hyperuricemia and it is usually manifested in the infantile period. In addition, it is also associated with growth failure, pubertal delay, anemia, platelet dysfunction, osteopenia, and pulmonary hypertension. Hepatocellular adenoma and renal dysfunction are frequent late complications. Delayed diagnosis and inappropriate therapy lead to many complications such as growth failure, osteoporosis, refractory gout, renal failure, hepatocellular carcinoma (HCC), and pulmonary hypertension. Here, two Korean sisters diagnosed with GSD Ia, aged 33 and 36 respectively, were described and compared to recent articles about four adults with late diagnosis of GSD Ia. One sister had typical manifestations of GSD Ia including short stature (height, 145 cm), multiple hepatic adenoma, chronic kidney disease stage IV, and severe osteoporosis, whereas the older sister had normal stature (162 cm), one tiny hepatic nodule, and normal renal function. Direct sequencing of G6PC in two sisters identified a homozygous splicing mutation, c.645G>T, which is a prevalent mutation in Korea. Interestingly, our cases and four adults from recent reports had asymptomatic mild hypoglycemia and various manifestations including renal failure, HCC, fatty liver, or uncontrolled hyperlipidemia. These adult cases represent not only heterogenous phenotype to genotype within family members with GSD Ia but also long-term complications such as gouty arthritis, renal failure, and osteoporosis in untreated adult GSD Ia patients. In addition, lactic academia and hypertriglyceridemia are good markers of GSD Ia to distinguish from metabolic disease.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.1
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• pp.24-30
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• 2017

Gorham-Stout disease is a rare disorder characterized by lymphovascular proliferation and destruction of osseous matrix. The etiology of this condition remains poorly understood. Chylothorax as a consequence of lymphatic leakage in thoracic cage may cause a severe life-threatening complication, accompanying respiratory difficulty. Currently, there is no standard management for this extremely rare condition. Here we describe a patient affected by Gorham-Stout disease successfully managed by the combined treatment of mTOR inhibitor and beta-blocker. A previously healthy 11-year-old female developed dyspnea and chest pain with a massive pleural effusion. The ligation of right thoracic duct and bilateral pleurodesis temporarily decreased her pleural effusion, which was aggravated repetitively and required frequent admission and tube thoracotomies. Along with bilateral pleural adhesiolysis with thoracotomy, the combined treatment of oral beta-blocker and mTOR inhibitor was commenced. After 1 month of oral medication, her pleural effusion was not increased and she was free of respiratory difficulty on room air without chest tubes. Over eleven months of treatment, no serious adverse reaction was noted and her condition has been stable with no further admission required.

• Clinical and Experimental Pediatrics
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• v.55 no.10
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• pp.397-402
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• 2012

Pelizaeus-Merzbacher disease (PMD) is a rare, X-linked recessive disorder characterized by dysmyelination in the central nervous system. PMD results from deletion, mutation, or duplication of the proteolipid protein gene (PLP1) located at Xq22, leading to the failure of axon myelination by oligodendrocytes in the central nervous system. PMD may be suspected when there are clinical manifestations such as nystagmus, developmental delays, and spasticity, and genetic analysis can confirm the diagnosis. Further diagnostic manifestations of the disease include a lack of myelination on brain magnetic resonance (MR) imaging and aberrant N-acetyl aspartate (NAA) and choline concentrations that reflect axonal and myelination abnormalities on phroton MR spectroscopy. We report 5 cases of PMD (in 1 girl and 4 boys). PLP1 duplication was detected in 2 patients. Brain MR analyses and MR spectroscopy were performed for all the patients. The brain MR images showed white matter abnormalities typical of PMD, and the MR spectroscopic images showed diverse patterns of NAA, creatinine, and choline concentrations. We propose that MR spectroscopic analysis of metabolic alterations can aid the PMD diagnosis and can contribute to a better understanding of the pathogenesis of the disease.