Neonatal Medicine

The Korean Society of Neonatology (대한신생아학회)
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A Novel Argininosuccinate Synthetase Gene Mutation in a Korean Family with Type I Citrullinemia

Citrullinemia Type I 환자의 가족에서 발견된 새로운 Argininosuccinate Synthetase 유전자 돌연변이

  • Ahn, Byoung-Whan (Department of Pediatrics, Daegu Fatima Hospital) ;
  • Kim, Hyun-Jeung (Department of Pediatrics, Daegu Fatima Hospital) ;
  • Park, Hyung-Doo (Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Won-Duck (Department of Pediatrics, Daegu Fatima Hospital)
  • 안병환 (대구파티마병원 소아청소년과) ;
  • 김현정 (대구파티마병원 소아청소년과) ;
  • 박형두 (성균관대학교 의과대학 삼성서울병원 진단검사의학과) ;
  • 김원덕 (대구파티마병원 소아청소년과)
  • Published : 2010.11.30
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Abstract

Citrullinemia type I is an urea cycle defect caused by mutations in the argininosuccinate synthetase (ASS1) gene. We report a novel argininosuccinate synthetase gene mutation in a Korean family with type I citrullinemia. Metabolic evaluation revealed significant hyperammonemia. Amino acid/acylcarnitine screening using tandem mass spectrometry showed high level of citrulline. Plasma amino acid analysis showed high level of citrulline and the urine organic acid analysis showed makedly increased level of orotic acid. To confirm diagnosis of citrullinemia we did mutation analysis of the ASS1 gene. The patient was found to have mutations of c.689G>C (p.G230A) and c.892G>A (p.E298K), which were new types of argininosuccinate synthetase gene mutation have never been reported in Korea. We report a novel case of argininosuccinate synthetase 1 gene mutation and suggest that the gene study to the family members is necessary to carry out when a patient is diagnosed as citrullinemia.

Citrullinemia는 요소 회로 이상으로 argininosuccinate synthetase의 결핍으로 기인한다. 저자들은 citrullinemia type I 환자와 그의 가족에서 새롭게 발견된 돌연변이를 경험하여 이를 보고하고자 한다. 환아는 광범위 신생아 선천성 대사이상 선별검사에서 citrulline이 고도의 증가 소견과 혈청 암모니아는 $982{\mu}mol/L$까지 증가 소견을 보였다. 혈청 아미노산 분석결과 citrulline 1,581 nmol/mL로 현저한 증가 소견을 보였으며 또한 소변 유기산 분석 검사결과 orotic acid가 3,566 mmol/mol Cr로 매우 증가된 소견을 보였다. Citrullinemia 확진을 위하여 환아와 가족에 대하여 ASS1 gene 검사를 시행하였다. 환아는 c.689G>C (p.G230A)와 c.892G>A (p.E298k)의 변이가 발견되어 ASS1 gene의 돌연변이에 의한 citrullinemia type I 으로 진단되었으며, 두 가지 돌연변이는 아직 국내에 보고된 적 없는 새로운 것으로 확인되었다. 국내에서 새롭게 발견된 citrullinemia type I 유전자를 보고하며 citrullinemia를 보인 경우 확진 및 유전상담을 위하여 가족 유전자 검사를 시행하는 것이 필요하다고 생각한다.

Keywords

References

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