• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.1
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• pp.47-51
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• 2016

Propionic acidemia (PA) is an autosomal recessively inherited disorder of the organic acid metabolism. It is caused by a deficiency of propionyl-CoA carboxylase (PCC). PCC is a heteropolymeric enzyme composed of ${\alpha}$- and ${\beta}$-subunits. The clinical symptoms of PA are heterogeneous and present vomiting, dehydration, hypotonia, and lethargy, and it can result in death. The typical presentations of neonatal onset PA are life-threatening metabolic acidosis and hyperammonemia. Here, we described a case of neonatal onset PA with mild clinical presentations. She was born to a healthy mother without complications. No significant illness was observed until nine days after birth. She started exhibiting poor oral feeding, vomiting, lethargy, and hypotonia at ten days old. Her laboratory results showed mild hyperammonemia and acidosis. The initial diagnosis was neonatal sepsis and she was treated with antibiotics. However, her clinical symptoms didn't improve. So we considered a metabolic disease. She was given nothing by mouth and intravenous hydration and nutrition support was performed. Propionylglycine and 3-hydroxypropionic acid were showed high concentrations in urine by gas chromatograph mass spectrometry (GC-MS). C3 level of acylcarnitine analysis elevated 10.4 uM/L (range, 0.200-5.00) in plasma. We took gene analysis for PA to be based on the symptoms and laboratory results. We detected PCCB gene mutation and diagnosed PA. She survived without severe neurologic defects and complications and was hospitalized only three times with upper respiratory tract infections for 7 years. We report a case of a ten days old neonate with PA presenting without severe metabolic acidosis and hyperammonemia who was effectively treated with early aggressive care and conventional methods.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.3
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• pp.165-170
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• 2015

Ornithine transcarbamylase (OTC) deficiency is a rare X-linked genetic disorder of urea synthesis in newborns. It is the most common urea cycle disorder and leads to elevated levels of ammonia in the blood. Excessive ammonia can cause various symptoms, including vomiting, lethargy, and coma. Boys have a more serious form of OTC deficiency than girls. If not treated immediately, severe OTC deficiency can lead to neurologic abnormalities, hyperammonemic coma, and death. Because late-onset OTC deficiency, which is more common in girls, presents mild symptoms, it is easy to miss diagnosis and prompt treatment. We describe an 11-month-old girl who presented periodic vomiting, intermittent lethargy, and seizure. She was diagnosed with OTC deficiency by elevated serum ammonia and urine orotic acid levels. Genetic analysis of the OTC gene revealed a missense mutation in exon 5 (c.418G>C). We reported an experience of exact diagnosis and successful treatment of late-onset OTC deficiency in our patient.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.16 no.3
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• pp.148-154
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• 2016

A urea cycle disorder is a condition caused by a defect of the enzymes in the urea cycle, and deficiency of ornithine transcarbamylase (OTC), which converts carbamoyl phosphate and ornithine into citrulline, is the most common type of the disorder. OTC deficiency induces the accumulation of precursors of urea, ammonia, and glutamine, leading to neurological symptoms including hypotonia, respiratory failure, seizure, lethargy, and coma and sometimes to death. Because OTC deficiency is inherited in an X-linked manner, typical symptoms such as vomiting, poor feeding, and lethargy appear mainly in male neonates. We recently had a case that presented with neonatal onset lethargy, vomiting, and apnea in a 4-day-old boy. He was diagnosed with OTC deficiency by biochemical phenotype, including hyperammonemia and an increased orotic acid level in the urine. Genetic analysis of the OTC gene showed a novel mutation c.780_781insCAGGCAGTGT (p.Ile261Glnfs*35). He was treated for hyperammonemia using continuous venovenous hemofiltration (CVVH) at 118 hours after birth. After 4 days of CVVH, his consciousness and blood ammonia concentration were normalized, and he was discharged at the age of 53 days. At around 12 months of age, bilateral femur fractures and osteomyelitis occurred in this patient. Two months after the fracture, he died of septic shock, insulin-resistant hyperglycemia, and multi-organ failure.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.1
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• pp.23-29
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• 2018

Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare autosomal recessive urea cycle disorder characterized by hyperammonemia. CPS1D is caused by mutations in the CPS1 gene on chromosome 2q35. Based on the age of onset, there are two phenotypes: the neonatal type and the delayed-onset type. The severity of clinical manifestation depends on the degree of CPS1 residual enzymatic activity, and can result in hyperammonemia and neurological dysfunction. We report a case of CPS1D in a neonate who developed vomiting, decreased consciousness and hyperammonemia at 25th day after birth. She showed excellent response to treatment including hydration, ammonia-lowering drugs and a low-protein diet without hemodialysis. Her growth, development and neurological outcomes were fair at the last follow-up at 17 months of age.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.35-39
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• 2015

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common mitochondrial fatty acid oxidation disorder which is inherited as an autosomal recessive pattern. MCAD deficiency is caused by mutations in the ACADM gene; medium-chain acyl-CoA dehydrogenase gene (ACADM; OMIM 607008) on chromosome 1p31 which encodes MCAD, the mitochondrial enzyme which catalyzes the first reaction in beta-oxidation of fatty acids with medium-chain length. Here, we describe one Korean pediatric case of MCAD deficiency, which was diagnosed during newborn screening by tandem mass spectrometry and confirmed by molecular analysis. The level of hexanoyl (C6), octanoyl (C8), decenoyl (C10:1) carnitine, and C8/C2 ratio was elevated. Homogenous c.1189T>A (p.Tyr397Asn) mutation of ACADM gene was identified by direct sequencing. He has been asymptomatic and has shown normal growth and development by 25 months of age without any intervention. There was no episode of metabolic acidosis during follow-up period.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.49-54
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• 2015

Multiple epiphyseal dysplasia (MED) is one of the more common skeletal dysplasias. MED is characterized by joint pain and stiffness, a waddling gait, and/or mild short stature in childhood. Radiographic findings include delayed and irregular ossification of the epiphyses in multiple joints. Mutations in at least six different genes (COMP, MATN3, COL9A1, COL9A2, COL9A3, and DTDST) can cause MED, and it can be either dominant or recessive inheritance. Molecular diagnosis is important for accurate prognosis and genetic counselling. COMP mutation is the most common form of MED in Western. But, MATN3 mutation was reported as the most common type of MED in Korea. Here, we describe a boy who was diagnosed as MED by clinical and radiological features. Hip radiograph of the patient was suggested MATN3 mutation. But knee radiograph was suggested COMP mutation. MATN3 and COMP mutations direct sequencing, but were no mutation. So we tested whole exome sequencing, but significant variant was not detected as known MED six genes mutations. The patient was diagnosed as having MED clinically and radiologically. Further study to identify the other responsible genes for MED is needed.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.15 no.1
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• pp.44-48
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• 2015

Mucopolysaccharidosis (MPS) IIIA is a lysosomal storage disorder caused by abnormalities of the enzyme Heparan N-sulfatase that is required for degradation of heparan sulfate. The patient in this study was a 5 year-old boy who presented with macrocephaly and developmental delay. Urinary excretion of glycosaminoglycan was increased (26 g/moL creatinine, reference range: <7 g/moL creatinine) and a distinct band of heparan sulfate was shown in electrophoresis. Heparan N-sulfatase activity was significantly decreased in skin fibroblasts (0.2 pmoL/min/mg protein, reference range: 9-64 pmoL/min/mg protein). PCR and direct sequencing analysis of the SGSH gene showed compound heterozygous mutations: c.1040C>T (p.S347F) and c.703G>A (p.D235N). This is the first report for a Korean patient with MPS IIIA who was confirmed by biochemical investigation and molecular genetic analyses.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.10 no.1
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• pp.59-66
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• 2010

Enzyme replacement of therapy (ERT) is one of the most promising therapeutic strategies for the treatment of lysosomal storage disorders. ERT is available in three types of Mucopolysaccharidosis (MPS): for MPS I (Aludrazyme$^{(R)}$), MPS II (Elaprase$^{(R)}$) and MPS VI (Naglazyme$^{(R)}$) patients who are over 5 years old. But recently, early diagnosis can be done by expert clinicians and even in prenatal case. We describe the case of ERT under 5 years old MPS patients. Up to June, 2010 in Samsung Medical Center, there are 6patients who were diagnosed as MPS and started ERT under 5 years old. 3 patients were MPS I, 3 patients were MPS II. 2 patient who was diagnosed as MPS I was female and others were male. Their age at diagnosis were 4 to 37month-old (4, 13, 16, 25, 27, 37 month-old) and they are now 9 to 60 month-old (9, 39, 32, 81, 60 month-old). The youngest patient was started ERT at 4 month-old and others were started at their 13 to 49 month-old (13, 29, 27, 28, 49 month-old). First manifested symptoms of patients were macrocephaly, kyphosis and coarse face appearance. Especially, in 2 of them, one was MPS I and the other was MPS II had elder brother with same disease. And the youngest one was diagnosed by the iduronate-2-sulfatase (IDS) gene analysis from chorionic villi sampling. His mother knew that she was a heterozygous carrier of IDS gene mutation because her younger brother died from MPS II. All of them confirmed as MPS by the enzyme assay in leukocytes and fibroblast skin culture. We started ERT with ${\alpha}$-L-iduronidase(Aldurazyme$^{(R)}$) to MPS I and did recombinant human iduronate-2-sulfatase (Elaprase$^{(R)}$) to MPS II patients as recommended dose as over 5 years old. But for MPS II patient who was 4 month old, we started ERT by recombinant human IDS (Elaprase$^{(R)}$) with reduced dose 0.1 mg/kg and increased dose every 2 weeks by 0.1mg/kg up to 0.5mg/kg IV infusion. During ERT, all patients had no adverse effects and the excretion of GAGs were decreased. We have evaluated other clinical symptoms such as liver/ spleen volume, heart function and neurologic evaluation. We describe a successful ERT to MPS I and MPS II patient under 5 years old without any adverse event. It indicates that ERT in young children are well tolerated and that it has several effects which may confer clinical benefits with long-term therapy.

• Proceedings of the KOR-BRONCHOESO Conference
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• 1991.06a
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• pp.28-28
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• 1991

후두암의 수직절제 수술후의 후두 재건 목적은 기관절개를 통하지 않고 후두를 통한 호흡이 가능하도록 하면서 연하시 기도흡인을 피하기 위한 sphincter 능력의 보존, 그리고 발성이 가능하도록 성대진동 mechanism을 재건하는데 있다. 오늘날 수많은 후두학자들에 의해서 고안 개발된 다양한 재건 방법이 있다. 연자는 광범위한 후두절제에 따른 큰 결손을 메우기 위해 bulky하면서도 점막 상피의 재생이 용이한 재건 피판으로 흉유돌근골막 피판을 이용하여 후두 결손부를 재건하여 보았다. 방법은 성견 3마리를 대상으로하여 thiopental sodium 정맥주사로 전신마취를 시행한 후 설골에서부터 흉골상까지 경부 정중앙의 피부를 절개하고 후두를 노출시켜 후두 수직절제술을 시행하였다. 흉유돌근과 흉골에 부착된 골막을 박리하여 흥유돌근골막 피판을 제작한 후 골막이 후두강 안쪽으로 되도록하여 골막연과 후두점막을 봉합하였다. 그리고 3, 5, 9개월에 후두적출술을 시행하여 병리조직학적 및 수술후 경과를 관찰하였다. 3실험견 모두 기관절개술 없이 후두를 통한 호흡이 가능하였고 흡입성 폐렴이나 피하기종등의 합병증없이 창상이 치유되었으며 발성도 양호하였다. 이식된 골막위로 신생혈관의 출현과 함께 점막재생이 잘되 있었다. 단지 봉합사 주위에 소량의 육아종이 관찰되었다. 조직학적으로는 섬유조직위로 편평상피가 재생되었으며 성문하부에서는 일부 섬모가 있는 호흡기 점막도 관찰되고 골막하부에 신생골 형성은 관찰할 수 없었다. 골막 피판은 그 유연성 때문에 결손부위의 점막연에 맞춰도 tension이 없고 공기 누출이 되지 않게 봉합이 가능할 뿐 아니라 점막이 재생할 수 있는 frame-work의 역할을 하는 것으로 사료되었다. 이상과 같은 사실로 미루어 흉유돌근 자체가 견실하고 골막에 혈류공급이 잘되어 창상치유에 좋을 뿐 아니라 큰 후두결손부의 재건이 가능하리라고 사료되었다.로서 몇가지 앞으로의 치료지침에 도움이 되는 결과를 얻었기에 보고하는 바이다. 1) 성별 분포는 남자 16(39 %), 여자 25 (61%)이었으며 1 : 1.5의 빈도를 보였다. 2) 연령 분포는 20대와 30대에서 남녀 모두 25명으로 대부분을 차지하였다. 3) 부식제의 종류는 빙초산이 26명 (63.4 %)으로 대부분을 차지하였고 염산 7 (17.1 %) Lye 3 (0.7 %) 의 순이었다. 4) 음독후 12시간내에 식도경술을 받은 환자가 3명(0.7 %) 12-24시간에 받은 환자가 17명(41.5 %), 24 - 48시간에 받은 환자가 11명(26. 8%)으로 48시간 내에 시행받은 환자가 전체의 75.6%를 차지하였다. 5) 식도경 검사상 나타난 식도화상은 Grade I 11명 (26.8%) G.ade II 18(43.9%) Grade III 7명(17.1%) 이었으며 Grade II 인 경우가 18명(43.9%)로 가장 많았으며 Grade I 11명(26.8 %), Grade III 7명 (17.1 %) Normal 5명 (12.2 %) 순이었다. 6) 조기 식도경 검사에서 41명중 oral cavity burn이 없었던 경우가 15명(36. 1 %) 이었으며, oral cavity burn이 있었던 26명중 5명(19 .2 %)에서 Esophageal burn이 없었다 특히 Esophageal burn의 Grade II, III 25명 중 9명(29.6 %)에서 oral cavity burn이 없었다. 7) 식도 부식중 환자의 치료 원칙으로 Grade I, II, III에서 항생제 및 보존적 치료를 하였으며 Grade I에선 oral feeding을 시켰고 Steroid는 경우에 따라 투여하였으며 Grade III에선 원칙적으로 사용치 않았다. 식도조영술은 Grade I II III에서 3주 후에 모두 시행하였다. 8) 3주 후 식도조영술을 실

• Journal of The Korean Society of Inherited Metabolic disease
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• v.18 no.2
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• pp.55-61
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• 2018

Orinithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle with resulting hyperammonemia, which is medical emergency in newborns.We recently had a case of a boy that presented with lethargy, seizure, hyperammonemia and hypocalcemia in neonatal period. He was diagnosed with OTC deficiency by two consequent ways which are initial biochemical phenotype including hyperammonemia and an increased orotic acid in his urine and genetic analysis of the OTC gene. The OTC gene showed a novel hemizygous mutation c.913C>T (p.Pro305Ser). He was treated by low protein intake, sodium benzoate, phenylbutyrate sodium, L-arginine, and continuous renal replacement therapy (CRRT). After discharge, he has a relatively good prognosis without notable developmental delay. For good prognosis, the duration of hyperammonemia should be shorten. And it can be reached by an early diagnosis. For early detection of OTC deficiency, targeted exome sequencing will be a important role as well as biochemical tests.