• 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.

• Clinical and Experimental Pediatrics
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• v.45 no.10
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• pp.1263-1272
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• 2002

Purpose : Rett syndrome(RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000-15,000 female births worldwide. It was initially described by Andreas Rett in 1966. RTT involves developmental regression characterized stereotypic hand movements, tremors, gait apraxia, seizures, deceleration of head growth after the age of 6-18 months. The disease-causing gene was identified as MECP2 on chromosome Xq28. We carried out mutational analysis of MECP2 genes in RTT patients. Methods : Whole blood(5 cc) of 34 sporadic RTT patients was collected in EDTA-anticoagulated tubes. Genomic DNA was extracted from peripheral blood using the E.Z.N.A. blood DNA kit. Four exons of the MECP2 gene were amplified by PCR in 34 Korean with RTT. We carried out PCR divided the exon three into two parts and the exon four into five parts. Primer sequences designed by Amir et al. in 1999 were almost used(AF030876). Sequencing primers used were the same as PCR. DNA sequencing reactions were performed using an ABI 377 DNA sequencer and ABI PRISM dye terminator cycle sequencing reaction kit(Perkin-elmer). The results were compared with the normal DNA sequence(X99686). To confirm the change of sequence on novel mutations, RFLP analysis was performed. Results : The MECP2 mutations were detected in 23(67.6%) of the 34 patients. The mutations consisted of 12 different types including nine missense and three nonsense mutations. Of these, three (L100V, G161E and T311M) mutations were newly identified. Most of the mutations discovered are located within MBD(39.1%) and TRD(39.1%). In this study, three(T158M, R270X, R306C) mutations were identified high frequency. Conclusion : MECP2 gene was also an important cause of Korean RTT patients. MECP2 gene study is an important tool for diagnosis of Korean RTT patients.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.103-111
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• 1985

Childhood epilepsy which has high prevalence rate and inception rate is one of the commonest problem encountered in pediatrician. In contrast with epilepsy of adult, in childhood epilepsy, more variable and varying manifestations are found because the factors of age, growth and development exert their influences in the manifestations and the courses of childhood epilepsy. Moreover epileptic children have associated problems such as physical and mental handicaps, psychologicaldisorders and learning disability. For these reasons pediatrician who deals with epileptic children experiences difficulties in making diagnosis and managing them. In order to improve understanding and management of childhood epilepsy, authors reviewed 103 cases of epileptic patients seen at pediatric department of Yeungnam University Hospital retrospectively. The patients were classified according to the type of epileptic seizure. Suspected causes of epilepsy, associated conditions of epileptic patients, age incidence and the findings of brain CT were reviewed. Large numbers of epileptic patients (61.2%) developed their first seizures under the age of 5. The most frequent type of epileptic seizure was generalized ionic-clonic, tonic, clonic seizure (49.5%), followed by simple partial seizure with secondary generalization (17.5%), simple partial seizure (7.8%), a typical absence (5.8%) and unclassified seizure (5.8%). In 83.5% of patients, we could not find specific cause of it, but in 16.5% of cases, history of neonatal hypoxia (4.9%), meningitis (3.9%), prematurity (1.9%), small for gestational age (1.0%), CO poisoning (1.0%), encephalopathy (1.0%), DPT vaccination (1.0%), cerebrovascular accident (1.0%) and neonatal jaundice (1.0%) were found, 30 cases of patients had associated diseases such as mental retardation, hyperactivity, delayed motor milestones or their combinations. The major abnormal findings of brain CT performed in 42 cases were cortical atrophy, cerebral infarction, hydrocephalus and brain swelling. This review stressed better designed classification of epilepsy is needed and with promotion of medical care, prevention of epilepsy is possible in some cases. Also it is stressed that childhood epilepsy requires multidisplinary therapy and brain CT is helpful in the evaluation of epilepsy with limitation in therapeutic aspects.

• Journal of Veterinary Clinics
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• v.10 no.1
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• pp.111-130
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• 1993

Lead toxicity was evaluated in forty-five cats on a balanced diet, Treated with 0(control), 10, 100(low), 1, 000, 2, 000, and 4, 000(high) ppm of lead acetate orally on a body weight basis. The objectives were to establish toxic dosage level of leaf in cats, to characterize changes in behavior and clinical pathology, and to demonstrate what blood lead concentrations correlate with the known dosages of lead. Some high dose cats showed projectile vomiting, hyperactivity, and seizures. The growth rates did not appear to be altered in any of the dosed groups. Normal blood lead concentration in cats were lower than that of humans, dogs, and cattle. Blood lead concentrations of 3 to 20$\mu\textrm{g}$/100$m\ell$ could be termed a 'subclinical' range in the cat. Clinical lead toxicity in cats may have blood lead concentrations ranging 20 to 120$\mu\textrm{g}$/100$m\ell$. Zinc protoporphyrin concentrations were proportional to lead dosages and a significant ZPP elevation, greater than 50$\mu\textrm{g}$/100$m\ell$, may be indicative of clinical lead toxicity. The enzyme aminolevulinic acid dehydratase showed an inverss dose response relationship for all lead dosages and a significant ZPP elevation, greater than 50$\mu\textrm{g}$/100$m\ell$, may be indicative of clinical lead toxicity. The enzyme aminolevulinic acid dehydratase showed an inverse dose response relationship for all lead dosages and appears to be a good indicator of lead exposure in cats. Urinary aminolevuliruc acid concentrations generally increased with lead dosage, but individual values varied. Hair lead concentrations rose proportionately to lead dosages. Lead at least in high doses appears to inhibit chemotactic activity of polymorphonuclear cells and monocytes. No consistent dose response relationships were observed in hemoglobin, RBC, WBC, neutrophil, lymphocyte, monocyte, and eosinophil counts. There were no consistent dose related changes in total protein, plasma protein, BUN, and ALT values. Reticulocyte counts did not increase significantly in most lead dosage levels, and are probably of little value in diagnosing lead toxicity in cats. The fact that no significant changes were found in nerve conduction velocities may support that there was no segmental demyelination resulting from lead ingestion. The lethal dose in cats appear to range from 60 to 150mg/kg body weight. A reliable diagnosis of lead poisoning can be made utilizing blood lead, ZPP, and ALAD, and hair lead.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.72-79
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• 2007

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.

• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.215-220
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• 2018

Purpose: Few reports have described the prognostic factors affecting the occurrence of subsequent unprovoked seizure in patients who present with febrile seizure (FS) after 6 years of age. We investigated the prognostic factors affecting the development of unprovoked seizures after FS among patients from Jeju Island. Methods: We included patients who developed FS after 6 years of age, who presented to our outpatient clinic between January, 2011 and June, 2017. Clinical data were obtained through chart reviews and phone call interviews. We used logistic regression analysis to analyze the risk factors associated with the occurrence of subsequent unprovoked seizure. Results: Of the 895 patients who presented to our hospital due to their febrile seizure, 83 developed FS after 6 years of age. Among them, 3 patients were prescribed antiepileptic drugs before the onset of the unprovoked seizure, and 4 patients developed an unprovoked seizure before 6 years of age. Thus, overall, 76 patients were included in the study. 51 patients developed first FS before 6 years of age. In the remaining patients, the first FS developed after 6 years of age. The mean observational period since the last outpatient follow-up visit was 3.2 years (median 3.04 years, range: 1.42-4.71 years). Among them, 21% developed an unprovoked seizure. Logistic regression analysis showed that electroencephalographic (EEG) abnormalities served as an independent risk factor for a subsequent unprovoked seizure. Conclusion: EEG is the proper diagnostic tool to predict the risk of a subsequent unprovoked seizure in patients with FS after 6 years of age.

• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.197-204
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• 2018

Purpose: West syndrome is a severe form of age-specific epilepsy that typically affects infants younger than 2 years of age with mitochondrial disease. We aimed to examine age-specific characteristics of the syndrome in these patients. Methods: We retrospectively analyzed 54 patients with West syndrome diagnosed with mitochondrial disease between March 2006 and March 2016. We compared treatment strategies and diagnostic and clinical variables between patients with early-onset (<6 months of age) and late-onset (${\geq}6$ months of age) seizures. Results: Seizure was the first symptom in 30 (90.9%) and 13 (65%) patients of the early-onset and late-onset groups, respectively (P=0.046). Delayed development was observed in 3 (9.1%) and 7 (35%) patients of the early-onset and late-onset groups, respectively (P=0.023). Lactate levels were normal in 17 patients (55%) of the early-onset group and 5 (25%) of the late-onset group (P=0.036), while initial brain magnetic resonance imaging (MRI) findings were normal in 23 (67.6%) and 8 (40%) patients of the early-onset and late-onset groups, respectively. Final MRI findings were abnormal in 32 patients (94.1%) of the early-onset group and 18 (90%) of the late-onset group (P=0.036). Although ketogenic diets reduced seizure frequency in both groups, the difference was not significant. Conclusion: There is no significant difference in epilepsy-related variables when patients are divided based on a cut-off age of 6 months. However, differences in the first symptom at onset and MRI findings were observed. Although lactate levels were not of significant diagnostic value in the early-onset group, they may be in the late-onset group.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.45-49
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• 2010

Purpose: Several radiopharmaceuticals were used for cisternography. But recently, due to more short acquisition time, high resolution than other radiopharmaceuticals like In-111 DTPA, we were using Tc-99m DTPA in cisternography. Using of Tc-99m DTPA for intrathecal, was not officially recognised by the FDA. And there are matters of aseptic meningitis, muscular tetany, seizures by inappropriate radiopharmaceuticals handling. So, it is necessary to prevent adverse reactions while handling the radiopharmaceuticals using in cisternography. Therefore, this study aims to evaluation of usefulness and procedures for safety of radiopharmaceuticals in cisternography. Materials and Methods: Subjects were 12radioactive tracer vials using in cisternography in 2008 Dec. 16 - 2009 Dec. 30. (1) Radioactive tracer Vial test - We were measured NaPertechnetate radiation dose and volume, normal saline volume for dilution, source volume and dose activity for patient injection. And then, calculated mass of pure DTPA. (2) Bacterial endotoxin test - We performed pyrogen test using by negative/positive control vials which was added normal saline 0.2 mL and added normal saline 0.1 mL, Tc-99m DTPA 0.1 mL in test control vial. And then, reacted by digital hot plate in $37.5^{\circ}C$ for 1 hour and compared of gel-clot in each control vials. (3) Compliance safety procedure - We were checked safety issues and wrote out a safety procedure exam sheet. Results: (1) Radioactive tracer Vial test - Mass of DTPA per dose for patient injection (mg) was 0.88 (mg) on average, and Mass of DTPA per volume for patient injection (mg) was 0.74 (mg) on average. (2) Bacterial endotoxin test - All control test vials showed negative reactions. (3) Compliance safety procedure - We were checked safety issues and wrote out a safety exam sheet in all the exams. So, there were no adverse reactions. Conclusion: We could examine easier to safety tests using by Techscan - DTPA (Mallinckrodt): CaNa3. Each test results were passed the safety tests and there are no adverse reactions. The use of Tc-99m DTPA for cisternography, always has been become an issue. Since it has occur adverse reaction while examine the cisternography using by Tc-99m DTPA, it needs to set up the 'Standard Operating procedures'.

• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.490-496
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• 1998

Purpose: We evaluated brain perfusion SPECT findings of MELAS syndrome and mitochondrial myopathy in correlation with MR imaging in search of specific imaging features. Materials and Methods: Subjects were five patients (four females and one male; age range, 1 to 25 year) who presented with repeated stroke-like episodes, seizures or developmental delay or asymptomatic but had elevated lactic acid in CSF and serum. Conventional non-contrast MR imaging and Tc-99m-ethyl cysteinate dimer (ECD) brain perfusion SPECT were Performed and imaging features were analyzed. Results: MRI demonstrated increased T2 signal intensities in the affected areas of gray and white matters mainly in the parietal (4/5) and occipital lobes (4/5) and in the basal ganglia (1/5), which were not restricted to a specific vascular territory. SPECT demonstrated decreased perfusion in the corresponding regions of MRI lesions. In addition, there were perfusion defects in parietal (1 patient), temporal (2), and frontal (1) lobes and basal ganglia (1) and thalami (2). In a patient with mitochondrial myopathy who had normal MRI, decreased perfusion was noted in left parietal area and bilateral thalami. Conclusion: Tc-99m ECD SPECT imaging in patients with MELAS syndrome and mitochondrial myopathy showed hypoperfusion of parieto-occipital cortex, basal ganglia, thalamus and temporal cortex, which were not restricted to a specific vascular territory. There were no specific imaging features on SPECT. The significance of abnormal perfusion on SPECT without corresponding MR abnormalities needs to be evaluated further in larger number of patients.