• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.1-8
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• 2015

Purpose: 3-methylcrotonyl CoA carboxylase deficiency (3MCCD) is leucine metabolic disorder caused by mutation in MCCC1 or MCCC2 gene. Clinical manifestations are variable, ranging from fatal neonatal onset to asymptomatic individuals. There is no retrospective study of Korean patients undergoing long-term treatment for 3MCCD. We reported this study to find out clinical symptoms and gene analysis of 3MCCD patients. Methods: This study was based on data of patients diagnosed with 3MCCD in Soonchunhyang university hospital between April 2009 and September 2013. We report clinical, enzymatic and mutation data of 3MCCD patients found by newborn screening. Results: In tandem mass spectrometry, 3-OH-isovalerylcarnitine (C5OH) of all patients increased. And all 7 patients were elevated 3-methylcrotonylglycine (3MCG) and 3-hydroxyisovaleric acid (3HIVA) in urine. MCCC mutation was identified in 2 patients and MCCC2 was mutated in 5 patients. We found mutation occurred in 8 different parts of nucleotide and such mutation caused 7 different types of changes in amino acid. All patients are on medication of L-carnitine and L-glycine. 4 patients are taking biotin. And 4 patients are eating leucine free formula. After starting treatment, there were no significant changes of urine 3MCG and 3HIVA levels. Conclusions: According to our data, MCCC2 gene mutation was more common than MCCC1 gene mutation. But the level of 3HIVA or 3MCG in urine has no correlation with phenotype. All patients has no symptoms and are shown normal development.

• Pediatric Infection and Vaccine
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• v.10 no.2
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• pp.200-207
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• 2003

Purpose : Malaria is known to have been eradicated for a few decades through persistent national health program in South Korea. However, malaria caused by Plasmodium vivax has started to reappear incidiously among military personnel near to DMZ since 1993. After then, the number of malarial cases have been increased abruptly year by year. We analyzed the children of indigenous malaria who were diagnosed by peripheral blood smear and malarial antibody test with regards to epidemiologic and clinical manifestations. Methods : The study 13 cases below 15 years of age, who were confirmed as vivax malaria during from January 2000 to August 2003. We retrospectively analyzed epidemiologic data, clinical manifestations, laboratory findings and therapeutic responses. Results : All of 13 cases were indigenous and tested positive for Plasmodium vivax. Of 13 patients, 9 were male and 4 were female. Mean age of onset was $9.5{\pm}3.6$ years old. Ilsan(n=9) was the most prevalent area, the most patients(n=11) were presented in summer (from June to August). A characteristic feature of periodic 3 day fever in patients with P.vivax infection was reported in only 2 among 13 cases. Thrombocytopenia was most prominent findings, which was accompanied by 12 of 13 patients and pancytopenia was appeared in 3 patients on this study. The therapeutic responses of hydroxycholoquine were very good in all cases, and abnormal laboratory findings were recovered and no relapse during follow-up period. Conclusion : Vivax malaria is indigenous in Korea near to DMZ, but recently endemic area seemed to be extended southward. Plasmodium vivax is the cause of indigenous malaria of children. As for children with high fever accompanying thrombocytopenia in endemic area of Korea, malaria must be included in differential diagnosis whether the type of fewer is periodic 3 day fever or not. Malaria antibody test is helpful as a screening test for malaria.

• Neonatal Medicine
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• v.18 no.1
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• pp.96-103
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• 2011

Purpose: Although infants with bronchopulmonary dysplasia (BPD) are at risk of developing secondary pulmonary hypertension (PH), which is associated with significant morbidity and mortality, little has been reported about the incidence, clinical course and prognosis of PH secondary to BPD in premature infants. This study was done to investigate the incidence, risk factors, clinical course, and the ultimate prognosis of PH developed secondary to BPD in very low birth weight infants (<1,500 g). Methods: Medical records of very low birth weight infant (VLBWI) admitted to Samsung Medical Center NICU from January 2000 to July 2007 were reviewed retrospectively. BPD was defined by Jobe's classification. The diagnosis of pulmonary hypertension was established as velocity of tricuspid valve regurgitation (TR) ${\geq}$3 m/s and a flattening of the intraventricular septum by conducting Doppler echocardiography. Results: The incidence of pulmonary hypertension was 6% in VLBWI with BPD and it developed in moderate to severe BPD. The diagnosis of pulmonary hypertension was made on postnatal 133 days (range 40-224 days) and the risk factors related to developing pulmonary hypertension were severe BPD, small for gestational age and outborn infants. The mortality rate was 57% and especially higher in severe BPD (70%). The time to recovery spent 3 months (range 1-10 months) in survived patients. Conclusion: Based on the results of this research, pulmonary hypertension secondary to BPD in VLBWI related to severity of BPD and had a poor prognosis. We expect that regular long-term echocardiography may be helpful in treating reversible in VLBWI with moderate to severe BPD.

• Clinical and Experimental Pediatrics
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• v.49 no.12
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• pp.1308-1314
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• 2006

Purpose : This study aimed to evaluate the usefulness of auditory evoked potential (AEP) in clarifying neuronal development in premature small for gestational age (SGA), and appropriate for gestational age (AGA) infants. Methods : A total of 183 premature infants who were born from August 2002 to July 2005, were examined with AEP. They were divided into three groups; AGA, symmetric-SGA and asymmetric-SGA group. Results : Statistically significant differences in the head circumference were observed in three groups. Among the risk factors, prevalence of hypoglycemia and hypoalbuminemia between AGA and asymmetric SGA infants were significantly different. V absolute peak latency (APL) in the right side of AGA infants was delayed were than that of asymmetric SGA infants. III-V interpeak latency (IPL) of asymmetric SGA infants was delayed more than that of symmetric SGA infants. Moreover, I-V IPL on both sides of symmetric SGA infants was shortened more than that of AGA infants. However, all the results of AEP were within the reference range, according to gestational age. Birth weight of, only asymmetric SGA, was related to the III APL on both sides and the III-V IPL on right side. Conclusion : This study shows that the values of APL and IPL of premature SGA infants are different than that of premature AGA infants. These data could be an indicator in evaluating the neurologic functions of small for gestational age infants.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.24 no.1
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• pp.37-42
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• 2024

Congenital adrenal hyperplasia (CAH) is a genetic disorder characterized by decreased cortisol secretion, with 21-hydroxylase deficiency being the most common type. It is uncommon for CAH to present primarily as cholestasis; therefore, when a patient presents with prolonged jaundice, it is difficult to suspect CAH immediately. In this report, we aim to share our experience with an exceptional case of 21-hydroxylase deficiency. A 28-day-old male visited the outpatient clinic due to prolonged jaundice and elevated 17α-hydroxyprogesterone (17-OHP) levels in the newborn screening test. Since he showed no other symptoms such as lethargy or vomiting, he underwent a routine blood test for jaundice and a retest of 17-OHP at the outpatient clinic. Two hours after the blood draw, he was found to have severe hyponatremia and hyperkalemia, so he was immediately admitted to the intensive care unit. After treatment with hydrocortisone, fludrocortisone, sodium chloride, and intravenous fluids, the cholestasis and electrolyte imbalances improved over time. He was diagnosed with 21-hydroxylase deficiency, salt-wasting type, which was confirmed by the ACTH stimulation test and genetic testing. It is important to make a prompt diagnosis of CAH to avoid missing critical timing. Therefore, CAH should not be overlooked, even if the patient does not exhibit typical symptoms.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.2
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• pp.79-85
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• 2016

Purpose: This study aimed to analyze genetic mutations, clinical manifestations, and treatment of patients with benign HPA in Korea. Methods: This case series study involved ten HPA patients who were referred to our hospital because of high phenylalanine concentration. We investigated their demographic features, clinical manifestations, and mutations of the PAH gene through direct DNA sequencing. Results: Among ten patients with benign HPA, two pairs of patients were related (father-daughter, mother-daughter relationship) cases, and all of them showed no specific clinical manifestations or notable past history. Their plasma phenylalanine levels ranged between 1.2 and 4.2 mg/dL. In the tetrahydrobiopterin (BH4) loading test, all patients were nonresponsive to BH4. In the confirmation test of PAH mutation analysis, we identified eleven different alleles out of twelve. The most common allele was R53H (c.158G> A). In addition, two novel PAH gene mutations, V423A (c.1268T>C) and V51A (c.152T>C), were identified. Although the patients did not receive any pharmacologic treatment or continuous phenylalanine restriction dietary therapy, their neurocognitive development was normal. Moreover, on serial outpatient follow-up tests, all patients maintained phenylalanine levels below 6 mg/dL. Conclusion: This study is the first in Korea to analyze benign HPA patients. All patients with benign HPA could maintain phenylalanine levels below 6 mg/dL with normal neurocognitive development, without continuous therapy. Therefore, performing mutation analysis and distinguishing benign HPA from phenylketonuria (PKU) are important to help improve life quality in patients with benign HPA by avoiding unnecessary lifelong therapy.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.2
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• pp.55-62
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• 2020

A 22-month-old girl who had taken iron supplements due to iron deficiency anemia, presented bloody mucoid stool for one month. She had a bruise at the right periorbital area due to minor trauma and hepatosplenomegaly. Laboratory studies showed anemia, thrombocytopenia, elevated alkaline phosphatase (ALP), hypophosphatemia, decreased haptoglobin, hypocomplementemia, negative direct/indirect Coomb's test, normal vitamin D3 level and high PTHi. Wrist x-ray showed no signs of rickets. The abdominal ultrasound showed only accessory spleen. Tandem mass spectrometry was normal. During follow up, bloody stool regressed after seven days of withdrawal of iron supplement and cow milk, and the total CO2 level had been within 15-20 mEq/L with normal anion gap. NGS (next generation sequencing) panel test for evaluation of renal tubular acidosis showed negative results. After low dose steroid and vitamin D supplements under the impression of hypocomplementemic vasculitis, thrombocytopenia, C3/C4, decreased haptoglobin, and elevated ALP level became normal. At 57 months of age, laboratory findings showed elevated liver enzyme, ALP and gamma-glutamyl transferase again. And liver cirrhosis with splenomegaly and diffuse renal disease were reported with abdomen CT scan. Liver biopsy reported macro- and micronodular cirrhosis. Urine organic acid profile showed elevated succinylacetone level. Whole exome sequencing revealed novel compound heterozygous mutations (NM_00137.2:c.107T>C, NM_00137, 2:c.614T>C) in FAH gene and confirmed by Sanger sequencing. Consequently, the patient was diagnosed as chronic hereditary tyrosinemia type I. She started low phenylalanine/tyrosine diet and nitisinone treatment. Our case had presented symptoms very slowly, which is the first case of chronic tyrosinemia type I in South Korea.

• Biomedical Science Letters
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• v.5 no.2
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• pp.181-190
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• 1999

To evaluate the usefulness of transforming growth factor-$\beta$1 (TGF-$\beta$1) as a new tumor marker, we determined the plasma TGF-$\beta$1 levels using sandwich ELISA assay in cancer patients. Patients with three most common adult cancers in Korea (stomach, liver and breast cancer) and children's cancers (leukemia and two kinds of solid tumor) were enrolled for the study. Furthermore, 39 individuals were subjected to age and sex-stratified plasma TGF-$\beta$1 analysis. No statistical difference was demonstrated with respect to age or sex. The mean plasma TGF-$\beta$1 level (16.0 ng/ ml) of stomach cancer patients was significantly higher than that (8.3 ng/ml) of controls. However, there was no difference among the mean plasma TGF-$\beta$1 levels of liver, breast cancer patients and controls. Seven of 16 patients (43.7%) with stomach cancer, one of 8 (12.5%) with liver cancer, and one of 7 (14.3%) with breast cancer showed higher TGF-$\beta$1 levels compared to controls. Plasma TGF-$\beta$1 concentrations of five leukemic children remained in the normal range regardless of the remission state. In contrast, initial high TGF-$\beta$1 levels from two children with solid tumors returned to normal range on surgical resection of tumors. From the above results, we could conclude that plasma TGF-$\beta$1 levels of apparently healthy individuals seem to be rather constant irrespective of difference in age or sex, and the plasma TGF-$\beta$1 has the limited value as a screening test for the diagnosis of aforementioned adult cancers because of its low sensitivity. Finally, additional studies need to be pursed for the large number of stomach cancer and pediatric solid tumor patients in order to reach a secure conclusion on the usefulness of plasma TGF-$\beta$1 as a tumor marker in these patients.