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

대한유전성대사질환학회 (The Korea Society of Inherited Metabolic Disease)
권호 표지

반복적인 저혈당으로 엑솜 시퀀싱을 통해 31개월에 진단된 Citrin 결핍증 1례

A Case of Citrin Deficiency Presenting with Recurrent Hypoglycemia: Diagnosed by Targeted Exome Sequencing

  • 김치우 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 황정윤 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 양아람 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 김진섭 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 이태헌 (녹십자 지놈 유전체 연구소) ;
  • 장자현 (녹십자 지놈 유전체 연구소) ;
  • 조성윤 (성균관대학교 의과대학 삼성서울병원 소아청소년과) ;
  • 진동규 (성균관대학교 의과대학 삼성서울병원 소아청소년과)
  • Kim, Chiwoo (Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Hwang, Jeongyun (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) ;
  • Lee, Taeheon (Green Cross Genome Corporation) ;
  • Jang, Ja-Hyun (Green Cross Genome Corporation) ;
  • 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)
  • 발행 : 2017.08.30
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초록

Citrin 결핍증은 요소회로 이상 질환 중 하나로, 7q21.3에 위치한 SLC25A13 유전자에 돌연변이로 발생하는 상염색체 열성 유전질환이다. 세 가지 표현형 중에 신생아 간내 담즙 정체형, 제 2형 시트룰린혈증은 잘 알려졌지만, 성장부진과 이상지질혈증형은 최근에 밝혀지고 있는 표현형으로 아직 우리나라에 보고된 적이 없다. 성장부진과 이상지질혈증형에서는 경미할 수는 있으나 식욕감소, 피곤함, 성장부진, 저혈당, 시트룰린 상승, 이상지질혈증, 젖산염/피루브산염 상승과 같은 이상이 관찰될 수 있다. 또한 저혈당으로 내원하였을 때 일반적인 검사로는 원인 규명이 어려울 수 있다. 저자들은 생후 30개월에 반복적인 저혈당으로 내원하여 소변 유기산 분석, 호르몬 검사와 같은 대사 이상 검사에서 명확한 특정 진단명이 의심되지 않아, 생후 31개월에 targeted exome sequencing을 통해 복합이형접합 SLC25A13 유전자 돌연변이[c.852_855del (p.Met285Profs*2), c.1177+1G>A]를 발견하여 성장부진과 이상지질혈증으로 발현한 citrin 결핍증을 우리나라에서 최초로 진단하여 보고하는 바이다.

Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene on chromosome 7q21.3, and a type of urea cycle disorder that causes hyperammonemia. Although neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, a type of citrin deficiency, have been described well in many articles for several decades, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), the other type of citrin deficiency, has been only identified recently. There was previously no case report about FTTDCD in Korea. Patients with FTTDCD could present with loss of appetite, fatigue, failure to thrive, hypoglycemia, hypercitrullinemia, dyslipidemia, and an increased lactate/pyruvate ratio. Routine evaluation may not reveal the cause of hypoglycemia caused by citrin deficiency. We recently had a case that presented with recurrent hypoglycemia in a 30-month-old boy. Chemistry profiling, urine organic acid analysis, plasma acylcarnitine analysis, and hormone studies indicated values within the normal range or non-specific findings. Mutation analysis to identify the cause of hypoglycemia identified the subject as a compound heterozygote carrying each of the c.852_855del ($p.Met285Profs^*2$), and c.1177+1G>A mutant alleles. We report here on this unusual case of citrin deficiency presenting with FTTDCD for the first time in Korea.

키워드

참고문헌

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