Journal of The Korean Society of Inherited Metabolic disease
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v.12
no.2
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pp.108-112
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2012
Glycogen storage disease type III (GSD type III, OMIM #232400) is a rare autosomal recessive disease caused by a deficiency of the glycogen-debranching enzyme (GDE) with a mutation in the AGL gene (OMIM *610860). It is known to be bifunctional enzyme, that is, having two independent catalytic activities; 1,4-${\alpha}$-D-glucan 4-${\alpha}$-D-glycosyltransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33) that occur at separate active sites on a single polypeptide chain. Most patients with GSD type III usually have symptoms related to decreased glycogenolysis in liver and muscles, such as hepatomegaly, hypoglycemia, failure to thrive, hyperlipidemia, muscle weakness and cardiomyopathy (type IIIa), however some patients show symptoms restricted to liver (type IIIb). GSD type III is diagnosed by enzyme test through liver or muscle biopsy or mutation analysis of the AGL gene. We report the case of GSD type III proven by gene study after liver biopsy, which revealed c.476delA, c.3444_3445insA in exon 6, 27 of AGL gene in Korean patient.
Seo, Joo-Hyun;Ma, Dae-Sung;Kim, Yong;Seo, Tae-Beom;Kang, Yong-Heack;Lee, Sang-Nam;Han, Gui-Young
Proceedings of the SAREK Conference
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2007.11a
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pp.570-575
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2007
The thermal performance of the air receiver filled with porous material for 5kWt dish solar collector installed in Inha University, Korea, is experimentally investigated. The diameter of the parabolic dish is 3.2 m, and its focal length is 2 m. It consists of 10 small pieces of glasses which have their own curvatures, and the effective reflecting area is 5.9 m2. The reflectivity of the glass is 0.95, and the thermal capacity of the system is about 5 kW thermal. The aperture diameter of the cylindrical-shape receiver which is made of stainless steel is 100 mm, and the height is 210 mm. A quartz window is installed at the receiver aperture to minimize the convective heat loss and prevent air leakages. In order to increase the heat transfer area, porous material (nickel-alloy) is inserted into the receiver. Air flows into the upper part of the receiver, which is the opposite side of the aperture. After the air flows through the inside receiver, that goes out of the receiver through 3 exits which are located near the aperture. The volumetric flow rates of air are varied from 600 to 1200 L/min. The thermal efficiency of the receiver ranges from 82% - 92% depending upon the flow rate. The results show that the system efficiency and receiver efficiency increase as the volume flow rate increases as expected. These results from the experiment will be useful for the applications to air heating receivers and solar reactors.
Journal of The Korean Society of Inherited Metabolic disease
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v.16
no.1
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pp.24-33
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2016
Mucopolysaccharidosis type VI (MPS VI) is a rare disease caused by the mutation of ARSB with prevalence range from 1/5,000 in northeast Brazil to 1/2,057,529 births in Czech Republic. In Asia, there is only one published figure in Taiwan of about 1/833,000 births. The exact prevalence in the Korean population is unknown, but we estimated the incidence of MPS VI is about 0.03/100,000 live births. Enzyme replacement therapy (ERT) with recombinant human Arylsulfatase B (rhASB) is a modality for the treatment of MPS VI that reduces the excretion of urine glycosaminoglycan (GAG) and improves joint motion, pulmonary function, and endurance. We presented the clinical features, molecular analysis and outcome of ERT in three Korean MPS VI patients. All patients had the typical characteristic clinical features of MPS IV. Short stature, dysostosis multiplex, corneal opacity and valvular heart disease were found at first presentation, while restrictive lung disease and carpal tunnel syndrome developed later in all patients. Molecular analysis demonstrated novel missense and nonsense mutation in the patients, including p.Ile 67Ser, p.Gly328Arg, $p.Arg191^*$, p.Asp352Asn, and p.Gly17Asp. After ERT, urine GAG was decreased in all patients. Skeletal involvement, corneal opacity, heart valve abnormalities and pulmonary function were not improved with ERT, but it had a better outcome on regarding joint motion and endurance. One patient underwent allogeneic bone marrow transplantation (BMT) prior to ERT, but their clinical response was not improved much after BMT. This study demonstrates clinical phenotypes and molecular analysis of the severe form of MPS VI in Korean patients.
Lim, Gina;Lee, Joo Hoon;Park, Young Seo;Kim, Kun Seok;Won, Hye-Sung
Clinical and Experimental Pediatrics
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v.52
no.4
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pp.464-470
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2009
Purpose : This study assessed the incidence and outcome of congenital anomalies of the kidney and urinary tract (CAKUT) detected by prenatal ultrasonography Methods : There were 906 cases of CAKUT detected by prenatal ultrasonography and postnatally confirmed at the Asan Medical Center from October 1989 to October 2007. We investigated the incidence and outcome of these cases by reviewing medical records retrospectively. Results : The order of incidence was hydronephrosis, multicystic dysplastic kidney (MCDK), duplex kidney, vesico-ureteral reflux (VUR), single kidney, hydroureteronephrosis, ectopic kidney, polycystic kidney, ureterocele, and posterior urethral valve (PUV). There were 520 cases (57.4%) of hydronephrosis, and 20% of these needed an operation due to significant obstruction. MCDK was associated with other CAKUT in 25.4% of all cases. Approximately 57.9% of duplex kidney cases needed surgical treatment due to ureterocele and VUR. VUR had a male: female ratio of 10:1. Two out of seven cases of autosomal recessive polycystic kidney had progressed to chronic renal failure. Patients with PUV were relatively uncommon, and one out of nine cases progressed to end-stage renal disease. Conclusion : CAKUTs detected by prenatal ultrasonography were composed of various anomalies, and almost all of them had a good outcome without any intervention. However, in some cases, recurrent urinary tract infection or renal failure occurred, especially in bilateral cases. For further management, a long-term multicenter study is needed to investigate the precise incidence and outcome of each anomaly in the general population.
Lee, Saeromi;Ahn, Chang Hyuk;Joo, Jin Chul;Song, Ho Myeon;Park, Jae Roh
Journal of Korean Society of Environmental Engineers
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v.36
no.12
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pp.828-836
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2014
The purpose of this study evaluates the water quality of artificial deep pool (ADP) during the late spring and summer. we monitored the water quality, as pH, dissolved oxygen (DO), temperature and conductivity at two stations (St. 1. open water, St. 2. in the ADP). The water quality in the ADP is very stable, and temperature and DO are lower than the open water (average value; temperature $1.4{\sim}3.2^{\circ}C$, DO 2.4~3.6 mg/L). In particular, daily variation of temperature in the open water showed above $4^{\circ}C$, but ADP remained stable. The water quality was analyzed using two-way analysis of variance (ANOVA). The results of the analysis showed difference about temperature, pH, DO, conductivity (two-way ANOVA, p<0.05). The ADP has created an aqua environment in thermal and DO gradients by depth. About 1.2 m, Temperature and DO were sharply decreased. The Rhodeus uyekii is dominant species in pond of this study. The ADP offers optimum water temperature ($16.5{\sim}18.5^{\circ}C$) to the Rhodeus uyekii about spawning. Consequently, the ADP offers stable habitat than open water for fish and aquatic organisms during the summer. It is also a good shelter for fish from a thermal stress.
To study the incidence and epidemiological factors of uterine cervical cancer in medical underserved area females, the questionnaire survey and Pap. smear for uterine cervical cancer was done on total 330 women who lived in Ullungdo from 5th to 12th August, 1998. The results were summarized as follows: The age distribution of subjects was 50s (24.5%), 60s (24.5%) and their educational level was “no schooling” (14.2%) and “elementary school” (42.7%). The first coital age of subjects was 19∼21yrs (30.0%), 16∼18yrs (13.9%) and the first pregnancy age was 22∼24yrs (36.7%) and 19∼21yrs (30.0%). The frequency of total pregnancy of subjects was over 5 times (52.1%). The frequency of total delivery was “3∼4 times” (35.5%) and “5∼6 times” (15.2%). 68.8% of subjects had experience of abortion and 80.0% of their husband were on the phimosis. 172 (52.1%) subjects had gynecological symptoms, their symptoms were leukorrhea (48.3%), pruritus (21.5%) and leukorrhea with pruritus (20.3%). 63.9% of total subjects have been received Pap. smear and the frequency of their Pap. smear was “only 1 time” (44.1 %), “irregularly” (30.3%) and the reason of respondents who have not been received Pap. smea. was “no specific symptom” (51.3%). Among the 330 women screened there were negative (45.8%), inflammation (47.3%), trichomoniasis and candidiasis (1.8%), atypical cells (4.5%) and dysplasia (0.6%).
Enzyme substitution with recombinant phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) is currently being explored for treatment of phenylketonuria (PKU), an autosomal recessive genetic disorder with mutations of the gene encoding phenylalanine-4-hydroxylase (EC 1.14.16.1). However, oral administration of PAL is limited because of proteolytic digestion in the gastrointestinal tract. The aim of this study was to determine the biochemical properties of PAL and delinate the susceptibility of wild-type PAL to pancreatic proteolysis by exploring several mutants, and to develop therapeutic drugs with PAL for PKU. The specific activity of PAL was assayed and its optimal pH, temperature stability, and intestinal protease susceptibility were investigated. Its $V_{max}$ values for phenylalanine and tyrosine were 1.77 and $0.47{\mu}mol$/ min/mg protein, respectively, and its $K_m$ values were $4.77{\times}10^{-4}$ and $4.37{\times}10^{-4}\;M$, respectively. PAL showed an optimal pH at 8.5, corresponding to the average pH range of the small intestine. It showed no loss of activity at $-80^{\circ}C$ for 5 months and possessed 93.4% of its activity under $4^{\circ}C$ for 4 wks. PAL was susceptible to chymotrypsin digestion and, to a lesser extent, to trypsin, elastase, carboxypeptidase A, and B. The trypsin and chymotrypsin cleaving sites were mutated to investigate protection from pancreatic digestion and the specific activities of these mutants were evaluated. The six mutants displayed low specific activities compared to the wild-type, suggesting that the primary trypsin and chymotrypsin cleaving sites may be essential for catalytic reaction. The PAL mutants could therefore be applied as a pretreatment modality without susceptibility to proteolytic attack, however, additional modification for enhancing enzymatic activity is needed to reduce the Phe levels effectively.
Journal of The Korean Society of Inherited Metabolic disease
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v.15
no.1
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pp.29-34
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2015
Citrullinemia type1 is an autosomal recessive disorder of the urea cycle characterized by neonatal or late onset of hyperammonemia caused by a deficiency of the enzyme argininosuccinate synthetase (ASS). An ASS1 deficiency demonstrates fatal clinical manifestations that are characterized by the neonatal metabolic coma and early death when untreated. It causes a broad spectrum of effects, ranging from a mild disorder to a severe mental retardation, epilepsy, neurologic deficits. An acute neonatal form is the most common. Infants are normal at birth followed by an acute illness characterized by vomiting, lethargy, seizures and coma. These medical problems are life-threatening in many cases. A later onset form is less frequent and may be milder than the neonatal form. This later-onset form is associated with severe headaches, visual dysfunction, motor dysfunction, and lack of energy. Citrullinemia type1 is caused by mutations in the ASS1 gene located on chromosome 9q34.1 that encodes argininosuccinate synthetase, the third enzyme of the urea cycle catalyzing the formation of argininosuccinic acid from citrulline and aspartic acid. The enzyme is distributed in tissues including liver and fibroblasts. This mutation leads to hyperammonemia, arginine deficiency and elevated citrulline level. In the urea cycle, argininosuccinate synthetase catalyses the conversion of citrulline and aspartate to argininosuccinate.. Here, we describe a female newborn patient with lethargy, rigidity and hyperammonemia who was diagnosed as citrullinemia type1 with a c.[421-2A>G], c.[1128-6_1188dup] mutation.
Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.
Sohn, Young Bae;Ahn, Sunhyun;Jang, Ja-Hyun;Lee, Sae-Mi
Journal of The Korean Society of Inherited Metabolic disease
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v.19
no.1
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pp.20-25
/
2019
Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (OMIM#201475) is an autosomal recessively inherited metabolic disorder of mitochondrial long-chain fatty acid oxidation. The clinical features of VLCAD deficiency is classified by three clinical forms according to the severity. Here, we report a case of later-onset episodic myopathic form of VLCAD deficiency whose diagnosis was confirmed by plasma acylcarnitine analysis and" multigene panel multigene panel sequencing. A 34-year old female patient visited genetics clinic for genetic evaluation for history of recurrent myopathy with intermittent rhabdomyolysis. She suffered first episode of rhabdomyolysis with acute renal failure requiring hemodialysis at twelve years old. After then, she suffered several times of recurrent rhabdomyolysis provoked by prolonged exercise or fasting. Physical and neurologic exam was normal. Serum AST/ALT and creatinine kinase (CK) levels were mildly elevated. However, according to her previous medical records, her AST/ALT, CK were highly elevated when she had rhabdomyolysis. In suspicion of fatty acid oxidation disorder, multigene panel sequencing and plasma acylcarnitine analysis were performed in non-fasting, asymptomatic condition for the differential diagnosis. Plasma acylcarnitine analysis revealed elevated levels of C14:1 ($1.453{\mu}mol/L$; reference, 0.044-0.285), and C14:2 ($0.323{\mu}mol/L$; 0.032-0.301) and upper normal level of C14 ($0.841{\mu}mol/L$; 0.065 -0.920). Two heterozygous mutation in ACADVL were detected by multigene panel sequencing and confirmed by Sanger sequencing: c.[1202G>A(;) 1349G>A] (p.[(Ser 401Asn)(;)(Arg450His)]). Diagnosis of VLCAD deficiency was confirmed and frequent meal with low-fat diet was educated for preventing acute metabolic derangement. Fatty acid oxidation disorders have diagnostic challenges due to their intermittent clinical and laboratorial presentations, especially in milder late-onset forms. We suggest that multigene panel sequencing could be a useful diagnostic tool for the genetically and clinically heterogeneous fatty acid oxidation disorders.
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