Isolated Glycerol Kinase Deficiency

최중완,이예승,배은주,오필수,박원일,이홍진,Choi, Joon Wan,Lee, Ye Seung,Bae, Eun Joo,Oh, Phil Soo,Park, Won Il,Lee, Hong Jin The Korean Society of Inherited Metabolic Disease 2013 대한유전성대사질환학회지 Vol.13 No.1

Glycerol kinase deficiency (GKD) is an X-linked recessive enzyme defect characterized biochemically by hyperglycerolaemia and glyceroluria. GK gene is located on the short arm of X chromosome 21.3 region tandemly with AHC gene, and DMD gene and there is a long deletion resulting in contiguous gene deletion syndrome. In Korea there was a report of contiguous gene deletion syndrome of adrenal hypoplasia congenita, glycerol kinase deficiency and Duchenne muscular dystrophy but no isolated glycerol kinase deficiency. This is the first case of isolated glycerol kinase deficiency confirmed by organic acid analysis and gene analysis in Korea. Glycerol kinase 결핍증(GKD)은 X-linked 열성유전되는 질환으로 생화학적으로 혈중 glycerol이 상승되고 소변으로 glycerol이 분비되는 질환이다. GK 유전자는 X chromosome 단완의 21.3 region에 위치하며, AHC gene과 DMD gene 사이에 직렬로 위치하고 있다. 만약 이부위에 긴 부분의 결손이 발생하면 이들 질환이 동시에 발생하게 되며, 이를 contiguous gene deletion syndrome이라고 부른다. 국내에서는 이 세 질환이 동시에 나타나는 contiguous gene deletion syndrome은 보고된 바 있으나 GK 결핍증만 단독으로 있었던 경우는 보고가 없었다. 저자들은 장염후의 고이화상태에서 저혈당과 의식의 혼탁으로 발현된 단독 GK 결손증을 보고하는 바이다.

소아청소년기의 케톤분해이상질환군

최중완,안석민,김영한,백준우,류혜원,배은주,이홍진,Choi, Joong Wan,Ahn, Seok Min,Kim, Young Han,Baek, Joon Woo,Ryu, Hye Won,Bae, Eun Joo,Lee, Hong Jin 대한유전성대사질환학회 2015 대한유전성대사질환학회지 Vol.15 No.3

Purpose: 3HB and AcAc are two ketone bodies that can be used as energy source in brain via succinyl-CoA:3-ketoacid CoA transferase (SCOT) and mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase, T2), called ketolysis. In case of malfunction of these enzymes, ketolysis cannot occur fluently causing various clinical manifestations. We want to know the numbers of patients and clinical manifestations of ketolytic defects in Korea. Material: For 67 patients of ketolytic defects out of 2794 patients that have done urine organic acid analysis, we analyzed clinical manifestations and age distribution. The study period was from January 2007 to September 2015. Method: To confirm persistency of ketonuria, repeated and loading organic acid analysis were done at least 1 week period interval. SPSS was used for statistical analysis. Result: Thirty patients in infantile period (2 M-2 Y), 31 patients in childhood period (2 Y-12 Y), 5 patients after adolescent period (>12 Y) and 1 in neonatal period were diagnosed during the study period. The most frequent chief complaint was seizure followed by seizure with developmental delay and developmental delay only. Conclusion: Ketolytic defects were not so rare in Korea. Major clinical manifestations are seizure and developmental delay or mental retardation. 목적: 우리나라 케톤분해이상질환군의 연령별분포, 임상양상 등을 알아보고자 본 연구를 시행하였다. 방법: 2007년 1월부터 2015년 9월 사이에 소변유기산분석을 시행하였던 2,794명의 환자 중에서 반복부하 유기산분석으로 진단된 67명의 케톤분해이상질환군환자들의 임상양상을 분석하였다. 결과: 케톤분해이상질환군 환자의 분포는 신생아기 1명, 영아기 30명, 소아기 31명, 청소년기 5명으로 나타났고, 가장 많은 주증상은 경련발작이었으며 발달지연을 동반한 경련발작, 발달지연 등이 뒤를 이었다. 결론: 우리나라의 발병빈도는 다른 나라에 비하여 높은 것으로 판단되며, 소아청소년과 의사들의 관심이 필요하다고 판단된다.

The corrected QT (QTc) prolongation in hyperthyroidism and the association of thyroid hormone with the QTc interval

이예성,최중완,배은주,박원일,이홍진,오필수 대한소아청소년과학회 2015 Clinical and Experimental Pediatrics (CEP) Vol.58 No.7

Purpose: Ventricular repolarization is assessed using the QT interval corrected by the heart rate (QTc) via an electrocardiogram (ECG). Prolonged QTc is associated with an increased risk of arrhythmias and cardiac mortality. As there have been few reports regarding the effects of hyperthyroidism on ventricular repolarization, we studied the association between serum free thyroxine (free T4 [fT4]) and thyroid stimulating hormone (TSH) levels and the QTc interval. Methods: Thirty-eight patients with hyperthyroidism (<30 years old) were included, and we used their clinical records and available ECGs (between August 2003 and August 2011) to evaluate the association between their fT4 and TSH levels and their QTc interval. In addition, we studied the ECGs of 72 age-matched patients with no hyperthyroidism (control group) and compared their data with that from the patients group. Results: The QTc duration in patients with hyperthyroidism was significantly prolonged compared to that in the control subjects (P<0.001). In addition, the number of hyperthyroid patients with abnormal prolonged QTc was significantly higher than that in the control group (P<0.001). Among the patients with hyperthyroidism, patients with prolonged QTc and borderline QTc had higher fT4 levels and there was positive correlation between their fT4 levels and their QTc interval (P<0.05). However, no correlation was observed between their TSH levels and their QTc interval. Conclusion: We report that hyperthyroidism is associated with QTc prolongation. The correlation between the fT4 levels and the QTc interval suggests that thyroid status is associated with QTc values and the risk of cardiac mortality.

한국인 소아청소년기 발달지연의 원인질환으로서의 유기산대사이상질환

이종윤,이예승,최중완,배은주,박원일,오필수,이홍진,Lee, Jong Yoon,Lee, Ye Seung,Choi, Joong Wan,Bae, Eun Joo,Park, Won Il,Oh, Phil Soo,Lee, Hong Jin 대한유전성대사질환학회 2012 대한유전성대사질환학회지 Vol.12 No.2

목적: 유기산대사이상질환군은 신경계의 급만성 손상을 일으킬 수 있는 선천성대사장애 질환군으로 현재까지 밝혀진 질환들만 60여 질환에 이르는 다양한 질환들이 포함되어 있는 질환군이다. 그동안 국내에서는 이에 대한 연구가 되지 못하였고, 정리된 바 없다. 이에 본 연구자들은 발달지연을 일으키는 유기산대사이상질환군에 대하여 알아보고자 본 연구를 시행하였다. 방법: 2007년 1월 1일부터 2011년 12월 31일까지 5년 동안 한림대학교 춘천성심병원 임상 유전학 연구소에 유기산분석이 의뢰된 3,345명의 환자들 중 발달지연의 정보가 있었던 738명의 환자들을 2개월에서 2세까지의 영아기, 12세까지의 소아기, 12세 이후의 청소년기의 3군으로 나눠서 발작의 유무에 따른 유기산혈증을 비교 분석하였다. 2개월 미만의 신생아기의 환자들은 제외하였다. 나머지 연령군의 경우는 발달지연만 있었던 군과 발달지연과 함께 발작이 있었던 경우에는 전신발작, 국소발작, 복합발작으로 나눠서 비교분석하였고, 발달지연만 있었던 군과 발달지연과 발작이 동시에 나타났던 군의 차이를 알아보았다. 결과: 전 연령군에서 발작의 유무와 상관없이 발달지연이 있었던 모든 환자를 정리하여보면 전체 환자는 738명이었고, 그중 398명(53.9%)은 유기산분석에서 정상소견을 보였고, 340명(46.1%)에서 유기산대사이상이 진단되었다. 가장 많았던 진단은 MRCD로 253명(34.3%)이었으며, 케톤체분해이상이 39명(5.3%)로 뒤를 이었고, 3-히드록시이소부티르산혈증이 26명(3.5%)이 있었으며, 제2형 글루타르산혈증이 8명(1.1%)이 있었고, 소수의 환자들이 진단된 경우로는 피루브산탈수소효소결핍증이 3명(0.4%), 3-메틸글루타르산혈증과 제1형 글루타르산혈증이 각각 2명(0.3%)씩 있었으며, 메틸말론산혈증, 에틸말론산혈증, 3-메틸크로토닐글리신혈증, HMG-CoA lyase 결핍증 및 지방산산화이상들이 각각 1명(0.1%), 씩 진단되었다(Table 5). 결론: 발달지연을 일으킬 수 있는 유기산대사이상질환군에서 가장 높은 빈도를 차지하고 있었던 것은 MRCD였으며, 그 뒤를 케톤체분해이상과 3-히드록시이소부티르산혈증이 잇고 있었으며, 그 외 다양한 질환들이 소수지만 진단되고 있으며, 이 질환들은 치료와 재발의 예방이 가능하다는 점에서 발달지연의 감별진단에 반드시 포함시켜야 된다고 판단된다. Purpose: Developmental delay is caused by very diverse etiologic diseases. Most chronic disorders has some influence on development. Chronic or acute disorders of CNS are main etiologic diseases of developmental delay. Up to now, over 60 diseases are included in organic acidopathies and most of them causes acute or chronic recurrent CNS damage and developmental delay. We have done this study to find out the importance of organic acidopathies causing developmental delay in Korean childhood and adolescent patients. Method: Retrograde analysis for 738 patients with developmental delay whose clinical informations are available and have done urine organic acid analysis for 5 years period, between Jan. 1st 2007 to Dec. 31th 2011. Statistical analysis was done with Student's t test using SPSS. Result: Out of 738 patients, 340 patients (46.1%) showed abnormalities on urine organic acid analysis. The most frequent disease was mitochondrial respiratory chain disorders (MRCD) (253, 34.3%), followed by ketolytic defects(39, 5.3%), 3-hydroxyisobutyric aciduria (26, 3.5%), glutaric aciduria type II (8, 1.1%), pyruvate dehydrogenase deficiency (3, 0.4%), 3-methylglutaric aciduria (2, 0.3%), glutaric aciduria type I (2, 0.3%), ethylmalonic aciduria (1, 0.15%), methylmalonic aciduria (1, 0.15%), HMG-CoA lyase deficiency (1, 0.15%), 3-methylcrotonylglycinuria (1, 0.15%), fatty acid oxidation disorders(1, 0.15%) and FAOD (1, 0.15%). Conclusion: Mitochondrial disorders are most frequent etiologic disease on all age group, followed by ketolytic defects and various organic acidopathies. The number and diversities of organic acidopathies emphasize meticulous evaluation of basic routine laboratory examinations and organic acid analysis with initial sample on every developmental patient.

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia

이예성,김희권,김혜림,이종윤,최중완,배은주,오필수,박원일,기창석,이홍진 대한소아청소년과학회 2014 Clinical and Experimental Pediatrics (CEP) Vol.57 No.5

Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonalresistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy(AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNASexons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia,hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature,obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeatedconvulsive episodes that started from the age of 2 months. A cranial computed tomography scanshowed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicatedmild mental retardation. Family history revealed that the patient’s maternal relatives, including hisgrandmother and 2 of his mother’s siblings, had features suggestive of AHO. Sequencing of the GNASgene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>Ttransversion results in an amino acid substitution from Gln to stop codon at codon 213 (p.Gln213*). Toour knowledge, this is a novel mutation in GNAS.