• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.199-204
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• 2009

Purpose : Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. Method : We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. Results : Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7 %) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). Conclusion : These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.55-62
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• 2017

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by beta-glucosidase deficiency. An 18 month-old male with hepatosplenomegaly, anemia, thrombocytopenia, and growth retardation referred to our hospital. The patient showed neurological symptoms, such as supranuclear gaze palsy and developmental delay. Bone marrow biopsy performed to rule out malignancy and the results revealed no malignant cell; however, abnormal histiocytes suggesting storage disease was noted. Based on hepatosplenomegaly, bicytopenia and unexplained neurologic manifestations, enzyme activity and genetic analysis were conducted emergently with a strong suspicion of GD. Beta-glucosidase activity in leukocyte was decreased. GBA sequencing to confirm the diagnosis revealed compound heterozygous pathogenic variants (i.e., c.754T>A, c.887G>A), both previously reported as the cause of neuronopathic GD. Under the diagnosis of type 3 GD, the patient immediately received enzyme replacement therapy (ERT). After 17 months of ERT, the size of spleen decreased, and hemoglobin and platelet count returned to normal. In addition, the activity of chitotriosidase and angiotensin converting enzyme decreased. However, myoclonic movement and generalized seizure occurred at the age of 19 months and antiepileptic drug was started. Other neurological deterioration including supranuclear gaze palsy and developmental delay also persisted. A new therapy to overcome neurologic problems should be developed for patients with type 3 GD.

• 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.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.1
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• pp.29-35
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• 2020

Joubert syndrome (JS) is a rare genetic disorder that is characterized by ataxia, hypotonia, developmental delay, respiratory abnormalities such as apnea-hyperpnea, and abnormal eye movements. The pathognomonic diagnostic finding is the "molar tooth sign" (MTS) on brain magnetic resonance imaging (MRI), described as cerebellar vermis hypoplasia or dysplasia, thick and horizontally oriented superior cerebellar peduncles, and an abnormally deep interpeduncular fossa. JS is characterized by genetic heterogeneity: pathogenic variants in over 30 genes have been identified to date. The CEP290 protein, which is on chromosome 12q21.3, is most frequently mutated in patients with JS, especially with renal involvement. Here, we report a case of JS in a 14-year-old male patient with end-stage renal disease. To the best of our knowledge, this is the first Korean report of a patient with JS due to CEP290 mutation (c.6012-12T> A) whose diagnosis was confirmed after repetitive MRI. We suggest consultation with an experienced neuro-radiologist and follow-up MRI studies to detect a "hidden" MTS if clinical findings suggest a diagnosis of JS. Furthermore, even in the absence of an MTS, whole exome sequencing should be considered.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.1
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• pp.1-13
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• 2020

Purpose: Gaucher disease (GD), which is the most prevalent lysosomal storage disorder worldwide, is caused by mutations in the glucocerebrosidase gene (GBA). GD is divided into three clinical subtypes based on the appearance of neurological symptoms. Type 1 GD is a chronic non-neuronopathic disease, and types 2 and 3 are acute neuronopathic and chronic neuronopathic forms, respectively. Neuronopathic GD types 2 and 3 are characterized by increased levels of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the brain, leading to massive loss of neurons. Methods: DNA damage and subsequent apoptosis of H4 cells were observed following neuroglioma H4 cell culture with GlcCer or GlcSph. Neuronal cell apoptosis was more prominent upon treatment with GlcSph. Results: When H4 cells were treated with GlcSph in the presence of tubacin, a histone deacetylase 6 inhibitor (HDAC6i), attenuation of both DNA damage and a reduction in the protein expression levels of GlcSph-induced apoptosis-associated factors were observed. Conclusion: These findings indicated that GlcSph played a prominent role in the pathogenesis of neuronopathic GD by inducing apoptosis, and that HDAC6i could be considered a therapeutic candidate for the treatment of neuronopathic GD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.2
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• pp.87-92
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• 2015

Mucopolysaccharidosis (MPS) is an inherited disease entity associated with lysosomal enzyme deficiencies. MPS type 2, also known as Hunter syndrome, has a characteristic morphology primarily involving x-l inked recessive defects and iduronate-2-sulfatase gene mutation. The purpose of this case report is to provide important clues to help pediatricians identify Hunter syndrome patients earlier (i.e., before the disease progresses). A 30-month-old boy showed developmental delay and decreased speech ability. Physical examinations revealed a flat nose and extensive Mongolian spots. Brain magnetic resonance images (MRIs) showed bilateral multiple patchy T2 hyperintense lesions in the periventricular and deep white matter, several cyst-like lesions in the body of the corpus callosum, and diffuse brain atrophy, which were in keeping with the diagnosis. Based on these findings, the patient was suspected of having MPS. In the laboratory findings, although the genetic analysis of IDS (Iduronate-2-sulfatase) did not show any pathogenic variant, the enzymatic activity of IDS was not detected. We could confirm the diagnosis of MPS, because other sulfatases, such as ${\alpha}$-L-iduronidase, were detected in the normal range. Early enzymatic replacement therapy is essential and has a relatively good prognosis. Therefore, early diagnosis should be made before organ damage becomes irreversible, and brain MRIs can provide additional diagnostic clues to help distinguish the disorder.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2057-2061
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• 2012

Backgrounds: Deficiency or excess of trace elements can induce body metabolic disorders and cellular growth disturbance, even mutation and cancerization. Since there are few studies of the effect of trace elements in bladder carcinoma in China, the aim of this study was thus to assess variation using a case control approach. Methods: To determine this, 81 patients with bladder carcinoma chosen as a study group and 130 healthy persons chosen as a control group were all assayed for urinary and serum trace elements (calcium [Ca], zinc [Zn], copper [Cu], selenium [Se]) using an atomic absorption spectrophotometer, and the results were analyzed by independent sample t tests. The correlative factors on questionnaires answered by all persons were analyzed by logistic regression. Results: The results showed urinary Ca, Zn and serum Cu levels of the study group to be significantly higher (P<0.05) than those of he control group. Serum Ca and Se levels of study group were significantly lower (P<0.05) than those of control group. Conclusion: There were higher urinary Zn and serum Cu concentrations in bladder carcinoma cases. Bladder carcinoma may be associated with Ca metabolic disorder, leading to higher urinary Ca and lower serum Ca. Low serum Se and smoking appear to be other risk factors for bladder carcinoma in China.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.6 no.1
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• pp.15-23
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• 2006

Purpose: Glycogen storage disease type III (GSD-III), is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme is amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), which is responsible for the debranching of the glycogen molecule during catabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different patients. In this study, we analyzed mutations of the AGL gene in three unrelated Korean GSD-III patients and discussed their clinical and laboratory implications. Methods: We studied three GSD-III patients and the clinical features were characterized. Sequence analysis of 35exons and part exon-intron boundaries of the AGLgene in patients were carried out by direct DNA sequencing method using genomic DNA isolated from patients' peripheral leukocytes. Results: The clinical features included hepatomegaly (in all patients), seizures (in patient 2), growth failure (in patients 1), hyperlipidemia (in patients 1 and 3), raised transaminases and creatinine kinase concentrations (in all patients) and mild EKG abnormalities (in patients 2). Liver transplantation was performed in patient 2due to progressive hepatic fibrosis. Administration of raw-corn-starch could maintain normoglycemia and improve the condition. 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 with c.1510_1511insT (p.Y504LfsX10), and patient 3 with c.3416 T>C (p.L1139P) and c.l735+1 G>T (Y538_R578delfsX4) mutations. Except R428K mutation, 4 other mutations identified in3 patients were novel. Conclusion: GSD-III patients have variable phenotypic characteristics resembling GSD-Ia. The molecular defects in the AGL gene of Korean GSD-III patients were genetically heterogeneous.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.101-109
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• 2015

Classic galactosemia (OMIM #230400) is an autosomal recessive inherited metaboic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) due to mutations in the GALT gene. If untreated, classic galactosemia is a potentially lethal disease presenting with poor feeding, vomiting, jaundice, liver failure, increased bleeding tendency, and septicemia leading to death within a few days after birth. Since 2006, expansion of newborn screening has been enabled the early diagnosis and early intervention of classic galactosemia in Korea. However, newborn screening, followup testing for confirmatory diagnosis and intervention for galactosemia continue to present challenges. In Korea, the prevalence of the classic galactosemia is considered relatively low compared to that of western countries. And the genotype is also clearly different from those of other population. Therefore, our own guideline for confirmatory diagnosis and intervention is needed. Here, the diagnostic algorithm for galactosemia after positive newborn screening result in Korea has been proposed. Considering the low prevalence and different mutation spectrum in Koreans, the early mutation analysis of GALT gene could be a useful tool for the accurate diagnosis and making any treatment decision.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.58-63
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• 2012

Classical galactosemia (OMIM# 230400) is an autosomal recessive disorder of carbohydrate metabolism, due to a complete loss in galactose-1-phosphate uridyltransferase (GALT; E.C.2.7.7.12) enzyme activity. It caused by mutations in the GALT gene (OMIM$^*$ 606999) that is located at chromosome 9p13. The GALT enzyme deficiency results in a build-up of galactose and galactose-1-phosphate, causing life threatening complications such as feeding problems, failure to thrive, hepatocellular damage, bleeding and sepsis. However, Duarte galactosemia, a variant form of GALT deficiency, has residual GALT enzyme activities in erythrocytes and do not have manifest the symptoms of classical galactosemia. Since the advent of newborn screening (NBS) for galactosemia, we rarely encounter such overwhelmingly ill newborns. The positive NBS with no symptoms indicates the possibility of Duarte galactosemia besides a simple false positive and it has to be differentiated from classical galactosemia which is a medical emergency. In Korea, detection rate of Duarte galactosemia is very low and its genetic information is restrictive, too. We report a case of monozygotic twins with D/G galactosemia compound heterozygote in proven by the mutational analysis of GALT gene, which revealed N314D polymorphism and -119 to -116 delGTCA.