Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
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The Ornithine Transcarbamylase (OTC) Deficiency Identified by a Novel Mutation

새로운 유전자 돌연변이로 확진된 Ornithine Transcarbamylase (OTC) 결핍증 1례

  • Song, Ari (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Kiwuk (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yang, Aram (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Jinsup (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Hyung-Doo (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Cho, Sung Yoon (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jin, Dong-Kyu (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 송아리 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 이기욱 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 양아람 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 김진섭 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 박형두 (성균관대학교 의과대학 삼성서울병원 진단검사의학과) ;
  • 조성윤 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 진동규 (성균관대학교 의과대학 삼성서울병원 소아청소년과)
  • Published : 2016.12.31
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Abstract

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.

요소 회로 대사 이상은 요소 합성에 관련된 효소의 결핍으로 인해 발생하는 질환으로, ornithine과 carbamylphosphate로부터 citrulline을 생성하는 과정에 관여하는 효소인 OTC 결핍증이 가장 흔하다. OTC 결핍증은 ammonia, glutamate, glutamine, alanine 등의 축적되면서 고암모니아 혈증 및 고글루타민 혈증으로 인한 신경학적 증상이 나타나게 되며, 근긴장 저하, 호흡 부전, 경련, 기면, 혼수로 진행하여 사망에 이르게 된다. 저자들은 생후 4일 경부터 구토와 함께 의식의 저하를 보인 환자에서 직열 질량 분석법을 통해 OTC 결핍증을 진단하였고, 증상 발생 31시간 만인 생후 118시간 째에 지속적 정정맥 혈액여과(continuous venovenous hemofiltration, CVVH)을 적용하여 고암모니아 혈증을 치료하였다. 또한 직접염기서열분석법을 통해 780번과 781번 염기 사이에 CAGGCAGTGT가 삽입되는 변이(c.780_781insCAGGCAGTGT (p.Ile261Glnfs*35))를 발견하였다. 환자는 4일 간의 CVVH 이후 혈중 암모니아 농도와 의식이 호전되어 생후 53일 째 퇴원하였으나, 생후 12개월 경 좌측 대퇴골의 골절과 골수염이 발생하였고, 이후 패혈증 쇼크, 고혈당, 다발성 장기부전으로 사망하였다. 이에 저자들은 OTC 결핍증 환자에서 CVVH 치료 및 패혈증과 당뇨를 경험하였고, 유전자 검사에서 이전에 보고된 바 없는 새로운 변이를 확인하였기에 증례를 보고하는 바이다.

Keywords

References

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