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

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

A Fatal Case of Neonatal Onset Carbamoyl Phosphate Synthetase I Deficiency with Homozygous CPS1 Mutation

동종 접합자 CPS1 돌연 변이를 동반한 신생아 발병형 Carbamoyl Phosphate Synthetase 1 결핍증의 치명적 사례

  • Yun, Jung Ha (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Shin, Seung Han (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Ko, Jung Min (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Ee-Kyung (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Han-Suk (Department of Pediatrics, Seoul National University College of Medicine)
  • 윤정하 (서울대학교 의과대학 소아과학교실) ;
  • 신승한 (서울대학교 의과대학 소아과학교실) ;
  • 고정민 (서울대학교 의과대학 소아과학교실) ;
  • 김이경 (서울대학교 의과대학 소아과학교실) ;
  • 김한석 (서울대학교 의과대학 소아과학교실)
  • Published : 2018.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Carbamoyl phosphate synthetase I (CPS1) deficiency is a rare autosomal recessive urea cycle disorder that causes hyperammonemic crisis. CPS1 is the first enzyme encoded by the CPS1 gene, which catalyzes the first step of the urea cycle. In CPS1 deficiency, ammonia, the toxic metabolite produced by the interruption of the urea cycle, is accumulated in the blood and brain, leading to hyperammonemic encephalopathy and irreversible brain damage. Here, we report a fatal case of neonatal-onset CPS1 deficiency in a 4-day-old girl presenting with recurrent seizures, who was revealed to be homozygous for c.1529delG ($p.Gly510Alafs^*5$).

Carbamoyl phosphate synthetase I (CPS1) 결핍은 상염색체 열성 유전을 하는 드문 요소회로 대사 이상 질환으로, 요소회로의 첫번째 단계 효소인 CPS1 결핍에 의해 고암모니아혈증이 발생하여 신경학적 이상을 초래하게 되는 질환이다. CPS1 결핍은 신생아기부터 성인까지 여러 시기에 발현될 수 있으나, 주로 신생아기에 증상이 발현하고, 신생아기에 증상이 발생할 경우 치명적인 고암모니아혈증이 발생하여 예후가 불량하여 사망에 이를 수 있다. 본 증례는 고암모니아혈증이 발견되어 투석 및 집중 치료하였음에도 심한 뇌손상이 빠르게 진행되어 사망한 신생아로, CPS1 유전자의 동종 접합자 변이를 확인하여 확진 되었으며 이후 시행한 가족 검사에서 부모와 생존한 자매가 모두 이종 접합자 보인자로 확인되어 보고하는 바이다.

Keywords

References

  1. Summar ML. Molecular genetic research into carbamoyl-phosphate synthase I: molecular defects and linkage markers. J Inherit Metab Dis 1998;21 Suppl 1:30-9. https://doi.org/10.1023/A:1005349306311
  2. Kurokawa K, Yorifuji T, Kawai M, et al. Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency. J Hum Genet 2007;52:349-54. https://doi.org/10.1007/s10038-007-0122-9
  3. Haberle J, Shchelochkov OA, Wang J, Katsonis P, Hall L, Reiss S, et al. Molecular defects in human carbamoy phosphate synthetase I: mutational spectrum, diagnostic and protein structure considerations. Hum Mutat 2011;32:579-89. https://doi.org/10.1002/humu.21406
  4. Diez-Fernandez C, Haberle J. Targeting CPS1 in the treatment of Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea cycle disorder. Expert Opin Ther Targets 2017;21:391-9. https://doi.org/10.1080/14728222.2017.1294685
  5. Summar ML, Koelker S, Freedenberg D, Le Mons C, Haberle J, Lee HS, et al. The incidence of urea cycle disorders. Mol Genet Metab 2013;110:179-80. https://doi.org/10.1016/j.ymgme.2013.07.008
  6. Keskinen P, Siitonen A, Salo M. Hereditary urea cycle diseases in Finland. Acta Paediatr 2008;97:1412-9. https://doi.org/10.1111/j.1651-2227.2008.00923.x
  7. Nakamura K, Kido J, Mitsubuchi H, Endo F. Diagnosis and treatment of urea cycle disorder in Japan. Pediatr Int 2014;56:506-9. https://doi.org/10.1111/ped.12439
  8. Choi R, Park HD, Yang M, Ki CS, Lee SY, Kim JW, et al. Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing. Ann Lab Med 2017;37:58-62. https://doi.org/10.3343/alm.2017.37.1.58
  9. Funghini S, Thusberg J, Spada M, Gasperini S, Parini R, Ventura L, et al. Carbamoyl phosphate synthetase 1 deficiency in Italy: clinical and genetic findings in a heterogeneous cohort. Gene 2012;493:228-34. https://doi.org/10.1016/j.gene.2011.11.052
  10. Uchino T, Endo F, Matsuda I. Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J Inherit Metab Dis 1998;21 Suppl 1:151-9. https://doi.org/10.1023/A:1005374027693