• Clinical and Experimental Pediatrics
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• 제49권11호
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• pp.1125-1139
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• 2006

In 1991, the Ministry of Health & Social affairs adopted a nationwide service program for neonatal screening of phenylketonuria, galactosemia, maple syrup urine disease, homocystinuria, histidinemia & congenital hypothyroidism for newborns delivered from low class pregnant women registered in health centers. Government decreased the test items from six to two, PKU & congenital hypothyroidism to increase test numbers with same budget from 1995. Government decided to test PKU & hypothyroidism for all newborns from 1997. 78 laboratories wanted to participate for neonatal screening test in 1999. Government didn't decide laboratory center for a certain district and placed responsibility on free competition. Government are planning to test 573,000 newborns from 1998, Government decided to screen 6 items PKU, congenital hypothyroidism, maple syrup urine disese, homocystinuria, galactosemia and congenital adrenal hyperplasia from 2006. 17 laboratores are participating now. The cost of screening test is supported by both the federal government and local government on a 40-60 basis. In case a patient with an inherited metabolic disease is diagnosed by screening of government program, special milk is provided at government's expense. Interlaboratory quality control was started 6 times a year from 1994. According to the government project, 3,707,773 newborns were screened. 86 PKU, 718 congenital hypothyroidism were detected. So incidence of PKU is 1/43,114 and congenital hypothyroidism is 1/4,612. Maeil dairy company produced new special formula for PKU, MMA and PA, MSUD, urea cycle disorder, homocystinuria, isovaleric acidemia from Oct. 1999. The cost benefit of performing screening procedures coupled with treatment has been estimated to be as high as 1.77 times in PKU, 11.11 times in congenital hypothyroidism than cost without screening. We are trying to increase the budget to test all newborns for Tandem mass sereening & Wilson disease from 2008. Now it is a very important problem to decrease laboratory numbers of neonatal screening in Korea. So we are considering 4-5 central laboratories which cover all newborns and are equipped with tandem mass spectrometer & enzyme immunoassay for TSH, 17OHP & enzyme colorimetric assay for galactose.

• 대한유전성대사질환학회지
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• 제15권2호
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• pp.98-100
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• 2015

경쇄 acyl-CoA 탈수소효소 결핍증(short chain acyl-CoA dehydrongenase deficiency, SCAD)은 미토콘드리아에 존재하는 효소 중 하나인 경쇄 acyl-CoA 탈수소효소(short chain acyl-CoA dehydrongenase, SCAD)의 결핍으로 인하여 지방산 산화의 장애를 초래하는 대사질환이다. 이 질환의 임상증상은 성장 부전, 대사성 산증, 저혈당, 발달 지연, 발작 및 신경 근육 증상, 근력 저하 등 매우 다양하다. 저자들은 무증상 신생아에서 신생아 선별검사를 통해 혈청 C4-butyrylcarnitine이 증가하고 소변의 ethylmalonic acid가 증가된 소견이 관찰되어 경쇄 acyl-CoA 탈수소효소 결핍증을 진단하였다. 생후 8개월까지 특이 증상 없이 추적관찰 중으로 정상적인 성장과 발달을 보였기에 이에 증례를 보고하는 바이다.

• Clinical and Experimental Pediatrics
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• 제59권sup1호
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• pp.45-48
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• 2016

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare autosomal recessive mitochondrial disorder of fatty acid ${\beta}$-oxidation, and is associated with mutations in the acyl-CoA dehydrogenase (ACADS) gene. Recent advances in spectrometric screening for inborn errors of metabolism have helped detect several metabolic disorders, including SCADD, without symptoms in the neonate period. This allows immediate initiation of treatment and monitoring, so they remain largely symptomless metabolic disease. Here, we report a 15-month-old asymptomatic male, who was diagnosed with SCADD by newborn screening. Spectrometric screening for inborn errors of metabolism 72 hours after birth revealed an elevated butyrylcarnitine (C4) concentration of $2.25{\mu}mol/L$ (normal, < $0.99{\mu}mol/L$). Urinary excretion of ethylmalonic acid was also elevated, as detected by urine organic acid analysis. To confirm the diagnosis of SCADD, direct sequencing analysis of 10 coding exons and the exon-intron boundaries of the ACADS gene were performed. Subsequent sequence analysis revealed compound heterozygous missense mutations c.164C>T (p.Pro55Leu) and c.1031A>G (p.Glu344Gly) on exons 2 and 9, respectively. The patient is now growing up, unretarded by symptoms such as seizure and developmental delay.

• Preventive Nutrition and Food Science
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• 제21권2호
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• pp.104-109
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• 2016

In the current study, we investigated the longitudinal association between dietary acid load and the risk of insulin resistance (IR) in the Tehranian adult population. This longitudinal study was conducted on 925 participants, aged 22~80 years old, in the framework of the third (2006~2008) and fourth (2009~2011) phases of the Tehran Lipid and Glucose Study. At baseline, the dietary intake of subjects was assessed using a validated semi-quantitative food frequency questionnaire, and the potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were calculated at baseline. Fasting serum insulin and glucose were measured at baseline and again after a 3-year of follow-up; IR was defined according to optimal cut-off values. Multiple logistic regression models were used to estimate the risk of IR according to the PRAL and NEAP quartile categories. Mean age and body mass index of the participants were 40.3 years old of $26.4kg/m^2$, respectively. Mean PRAL and NEAP scores were -11.2 and 35.6 mEq/d, respectively. After adjustment for potential confounders, compared to the lowest quartile of PRAL and NEAP, the highest quartile was accompanied with increased risk of IR [odds ratio (OR)=2.81, 95% confidence interval (CI)=1.32~5.97 and OR=2.18, 95% CI=1.03~4.61, respectively]. Our findings suggest that higher acidic dietary acid-base load, defined by higher PRAL and NEAP scores, may be a risk factor for the development of IR and related metabolic disorders.

• Childhood Kidney Diseases
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• 제22권2호
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• pp.52-57
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• 2018

Purpose: Rhabdomyolysis is a metabolic disorder in which the content of damaged muscle cells is released into plasma. Its manifestations include asymptomatic, myalgia, gross hematuria, and complications of acute kidney injury. Because of limited data on rhabdomyolysis in children, we performed this study to determine clinical characteristics of rhabdomyolysis in children. Methods: We retrospectively reviewed the records of patients with rhabdomyolysis who were treated at the Pusan National University Children's hospital from January 2011 to July 2016. The diagnostic criteria were serum myoglobin level of ${\geq}80ng/mL$, exclusive of acute myocardial injury, cardiac arrest, and brain damage. Results: Forty-five patients were enrolled; mean age, $116{\pm}68$ months. Of these, 35 were boys and 10 were girls. Twenty-six patients experienced myalgia and 12 patients showed gross hematuria. Among these, seven patients initially had both myalgia and gross hematuria. The most common causes of rhabdomyolysis were infection, physical exertion, prolonged seizures, metabolic abnormalities, and drug addiction. Acute kidney injury (AKI) was the most common complication, followed by disseminated intravascular coagulation. Thirty-seven patients improved with sufficient fluid supply but two patients underwent hemodialysis due to deterioration of kidney function. Gross hematuria, positive occult blood test, and positive urine protein were more common in patients with AKI than in those without AKI. Conclusions: In children, infection was the most common cause of rhabdomyolysis. Most patients recovered by sufficient fluid therapy. However, in severe cases, especially in patients with underlying kidney disease, hemodialysis may be necessary in the present study.

• 대한유전성대사질환학회지
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• 제1권1호
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• pp.23-27
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• 2001

Fanconi-Bickel Syndrome (FBS) is a rare autosomal recessive disorder of carbohydrate metabolism recently demonstrated to be caused by mutations in the GLUT 2 gene for the glucose transporter protein 2 expressed in liver, pancreas, intestine, and kidney. This disease is characterized by hepatorenal glycogen accumulation, both fasting hypoglycemia as well as postprandial hyperglycemia and hyperglactosemia, and generalized proximal renal tubular dysfunctions. We report the first Korean patient with FBS diagnosed based on clinical manifestations and identification of a novel mutation in the GLUT 2 gene. She was initially diagnosed having a neonatal diabetes mellitus due to hyperglycemia and glycosuria at 3 days after birth. In addition, newborn screening for galactosemia revealed hypergalactosemia. Thereafter, she has been managed with lactose free milk, insulin therapy. However, she failed to grow and her liver has been progressively enlarging. Her liver functions were progressively deteriorated with increased prothrombin time. Liver biopsy done at age 9 months indicated micronodular cirrhosis with marked fatty changes. She succubmed to hepatic failiure with pneumonia at 10 months of age. Laboratory tests indicated she had generalized proximal renal tubular dysfuctions; renal tubular acidosis, hypophosphatemic rickets, and generalized aminoaciduria. Given aforementioned findings, the diagnosis of FBS was appreciated at age of 2 months. The DNA sequencing analysis of the GLUT 2 gene using her genomic DNA showed a novel mutation at 5th codon; Lysine5 Stop (K5X).

• 대한유전성대사질환학회지
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• 제15권3호
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• pp.110-117
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• 2015

All infants should be screened for phenylketonuria (PKU) within the three days of life, in order to allow timely dietary intervention to protect children with PKU from neurologic damage in Korea. A commonly used cut-off level for diagnosis of PKU is $240{\mu}mol/L$ (4 mg/dL). Up to 2% of cases of hyperphenylalaninemias (HPA) detected by the screening test will account for a disorder of $BH_4$ metabolism. Therefore, analysis of blood or urinary pterins is essential, backed up with measurement of DHPR activity, as this allows differentiation of $BH_4$ disorders. A $BH_4$ loading test and measurement of neurotransmitters in CSF provide further important information to the severity of $BH_4$ deficiency and $BH_4$ loading test can detect patients with $BH_4$ deficiency and $BH_4$ responsive PKU. Several protocols for $BH_4$ loading test have been described, involving treatment with $BH_4$ for periods ranging from 1 day to 1 month, and using doses of $BH_4$ of 10-20 mg/kg. There is general agreement that a reduction on blood phenylalanine of at least 30% in response to $BH_4$ loading indicates a clinically significant effect, although in some tests a lower cut-off value may be defined for individual patients, or no specific cut-off value is proposed. The frequency of $BH_4$ responsiveness is highest in patients with mild HPA and mild to moderate PKU resulting from PAH mutations with residual activity.

• 대한유전성대사질환학회지
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• 제15권3호
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• pp.155-159
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• 2015

시트룰린혈증 2형은 SLC25A13 유전자 변이에 의한 시트린 결핍증으로 생기는 상염색체 열성 유전질환으로 고암모니아혈증, 시트룰린혈증, 저혈당증, 갈락토즈혈증 등의 생화학적 이상소견이 동반 되는 질환이다. 임상적으로 영아형인 '시트린 결핍증에 의한 신생아 간내 담즙정체(NICCD)', 소아형인 '시트린 결핍에 의한 성장 부진과 이상지방혈증(FTTDCD)', 성인형인 '성인기 발병 시트룰린혈증 2형(CTLN2)'의 세 가지 형태로 나타난다. 그 중 NICCD는 영아기 발생 간내 담즙 정체, 간 기능 장애, 저단백혈증, 저혈당증, 성장부진, 지방간 등의 증상이 나타나고 임상증상, 생화학적 검사이상을 통해 질환을 의심한 후 SLC25A13 유전자 분석 검사를 통해 확진 할 수 있다. 저자들은 생후 35일에 시트룰린혈증으로 방문한 영아에서 NICCD와 부합되는 생화학적 검사 소견과 SLC25A13 유전자 염기서열 분석 검사상 c.[1817G>A]과 [?] (p.[W606*];[?])이형접합변이로 NICCD를 진단하였기에 보고하는 바이다.

• 대한유전성대사질환학회지
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• 제11권1호
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• pp.88-98
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• 2011

Lesch-Nyhan syndrome is a X-linked recessive disorder caused by a deficiency of the enzyme hypoxanthine-guanidine phosphoribosyltransferase (HPRT), enzyme to recycle purines. Case history: born induced vaginal delivery at 40 weeks complicated by premature membrane ruputure, body weight 2.820 gm. He showed failure to thrive showing severe protein aversion like milk products and pink daper. Developmental delay revealing rolling over at 10.5 month, followed by regression. Seizure at 2 months, His poor oral feeding was lifelong problem. Weak crying, spastic, choreoathetoid movement. Self mutilating behavior noted and diagnosed at age 3 years. No family history of consanguinity and neurological disorders. Method: Laboratory test, physical exam, imaging study and molecular. Clinical follow up Treat ment with allopurinol. Result: uric acid 10.5 mg/dL (N 3.5-7.9), APRT 151.1uM/ min/ml pro(25.7-101), HPRT 7.6 (N 233.5-701) and c.151C>T hemizygote (p,Arg51X). Abdominal sonogram showed staghorn calculi in both kidneys, brain MRI brain atrophy. Clinical follow up showed, seizure at 2 mo, developmental delay (head control and, rolling over at at 11mo, pointing body part at 2 yr 7 mo, eye hand coordination at 2 y 11mo,creeping at 3 y 7 mo, speaking words at 6 y 6 mo ),and developmental regression at 3 yr of age. Sleeping problem including insomnia and severe constipation. Self mutilating behavior (lip bite) started at 2.5 yr, neurologic sx including intermittent upward gaze accompanied by swallowing difficulty at 3 y 7 mo grand mal seizure at 4.5 yr and spastic extremity and trunchal hypotonia and choleoathetoid movement and ataxia at 6.5 yr. Scoliosis with severe spasticity at 9 yr 9 mo. Acute life threatening episode with irregular breathing at 9 yr and 9 mo, Emaciation and nephrolithiasis and recurrent pneumonia. Died suddenly at 10 yr 3 mo. Conclusion: life long feeding problem, chronic gut motility dysfunction, sleeping difficulty and progressing neurologic deterioration and nephrolithiasis despite normal serum uric acid maintence by allopurinol treatment.

• 대한유전성대사질환학회지
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• 제12권1호
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• pp.42-48
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• 2012

폼페병은 GAA 유전자의 돌연변이로 인해 acid ${\alpha}$-glucosidase (GAA) 효소가 완전 혹은 부분적으로 결핍되어 발생하는 드문 리소좀 축적질환의 하나이다. 전형적인 영아형 폼페병은 다기관을 침범하여 빠르게 진행하는 질환으로, 근긴장도 저하, 전신적인 근력 감퇴 및 비후성 심근병증이 주된 임상 양상이며 치료를 받지 않으면 보통 1-2세경에 사망에 이르게 된다. 재조합 GAA 효소 대체 요법은 이러한 영아형 폼페병 환자에서 병의 진행 경과를 늦추고 예후를 호전시키는데 효과적임이 이미 확인되었다. 본 연구에서는 단일 기관에서 경험한 비후성 심근병증으로 발현된 혈연 관계가 없는 세 명의 한국인 폼페병 환자의 임상 양상 및 유전학적 양상과 더불어 단기간의 효소 대체 요법 효과를 보고하고자 한다. 효소 대체 요법이 도입된 이래 영아형 폼페병의 자연 경과가 매우 호전된 바, 보다 조기에 진단하여 효소 대체 요법을 시작하는 것이 환자의 예후를 호전시키고 합병증을 최소화하는데 결정적일 것으로 생각된다.