Neonatal Medicine

The Korean Society of Neonatology (대한신생아학회)
권호 표지
DOI QR코드

DOI QR Code

Three Cases of Mitochondrial Disorders in the Neonatal Period

신생아기에 진단된 미토콘드리아 질환 3례

  • Kim, Yoon-Hee (Departments of Pediatrics, College of Medicine, Yonsei University) ;
  • Lee, Young-Mock (Departments of Pediatrics, College of Medicine, Yonsei University) ;
  • Namgung, Ran (Departments of Pediatrics, College of Medicine, Yonsei University) ;
  • Kim, Jeong-Eun (Departments of Pediatrics, College of Medicine, Yonsei University) ;
  • Lee, Soon-Min (Departments of Pediatrics, College of Medicine, Yonsei University) ;
  • Park, Kook-In (Departments of Pediatrics, College of Medicine, Yonsei University) ;
  • Kim, Se-Hoon (Departments of Pathology, College of Medicine, Yonsei University) ;
  • Lee, Jin-Sung (Departments of Clinical Genetics, College of Medicine, Yonsei University)
  • 김윤희 (연세대학교 의과대학 소아과학교실) ;
  • 이영목 (연세대학교 의과대학 소아과학교실) ;
  • 남궁란 (연세대학교 의과대학 소아과학교실) ;
  • 김정은 (연세대학교 의과대학 소아과학교실) ;
  • 이순민 (연세대학교 의과대학 소아과학교실) ;
  • 박국인 (연세대학교 의과대학 소아과학교실) ;
  • 김세훈 (연세대학교 의과대학 병리학교실) ;
  • 이진성 (연세대학교 의과대학 임상유전과)
  • Published : 2010.11.30
⟨ Previous Next ⟩

Abstract

Little is known about neonatal mitochondrial disease, though mitochondrial metabolic disorders may often present in the neonatal period because of the high energy requirement of neonate. In newborn period, common presentations are not specific and the disease course may be rapid and fatal. In this study, we report three cases of neonatal mitochondrial disease. The first case was strongly suspected because of sudden seizure and mental change with severe lactic acidosis, and multiorgan failure. Plasma lactate/pyruvate (L/P) ratio was increased to 55.6 with marked lactic aciduria and increased plasma alanin up to 2,237 nmol/mL. In the second patient, a peritoneal dialysis was performed for acute adrenal and renal failure, but metabolic acidosis persisted. Plasma L/P ratio was increased to 23.9, and MRC I (mitochondrial respiratory chain defect) was diagnosed through the enzymatic analysis of the muscles. The third case showed repetitive episode of lactic acidosis during the first two months of life, hypotonia, failure to thrive and feeding difficulties. We found markedly increased cerebrospinal fluid L/P ratio up to 57 though plasma L/P ratio(19.4) was borderline with increased plasma lactate. The lactate peak was prominent in brain magnetic resonance spectroscopy (MRS). MRC II was confirmed through muscle biopsy. Plasma lactate level and lactate peak of brain MRS were normalized after conservative treatment.

신생아에서의 미토콘드리아 질환은 임상 증상이 다양하고 비특이적이라 진단이 어렵고, 치명적으로 생존율이 낮기 때문에 이에 대한 연구는 미비하다. 본 연구에서는 신생아기에 미토콘드리아 질환 소견으로 치료한 3례를 보고하였다. 증례 1은 갑작스럽게 발생한 강직성 경련, 의식 소실 및 심한 대사성 산증과다기관 기능 부전으로 미토콘드리아 병증이 의심되었다. 혈장내 젖산/피루브산염 비가 55.6, 아미노산 검사에서는 알라닌 2,237 nmol/ml로 증가되었다. 증례 2에서는 급성 부신기능부전과 급성 신부전으로 복막 투석을 하였으나 대사성 산증이 지속되었다. 혈장 내 젖산/피루브산염 비가 23.9였고, 근 조직을 이용한 효소 분석에서 1번 복합체의 호흡 사슬 결함이 진단되었다. 증례 3은 출생 후 2개월간 반복되는 대사성 산증과 기면, 수유 곤란 소견을 보였다. 혈장 내 젖산/피루브산염 비가 19.4로 정상 범위의 경계에 있었으나 뇌척수액 검사상 젖산/피루브산염 비가 57로 현저하게 증가된 소견을 보였고, 뇌 자기 공명 분광경 검사에서 lactate peak 소견을 보였다. 근 조직을 이용한 효소 분석에서 2번 복합체의 호흡 사슬 결함이 진단되었다. 세증례 모두에서 미토콘드리아 질환 소견으로 비타민, 조효소 Q10 및 L-카르니틴을 투여하였다.

Keywords

References

  1. Sue CM, Hirano M, DiMauro S, De Vivo DC. Neonatal presentations of mitochondrial metabolic disorders. Semin Perinatol 1999;23:113-24. https://doi.org/10.1016/S0146-0005(99)80045-7
  2. Stern HJ. Lactic acidosis in paediatrics: clinical and laboratory evaluation. Ann Clin Biochem 1994;31( Pt 5):410-9. https://doi.org/10.1177/000456329403100502
  3. Haas RH, Parikh S, Falk MJ, Saneto RP, Wolf NI, Darin N, et al. Mitochondrial disease: a practical approach for primary care physicians. Pediatrics 2007;120:1326-33. https://doi.org/10.1542/peds.2007-0391
  4. DiMauro S, Schon EA. Mitochondrial respiratory-chain diseases. N Engl J Med 2003;348:2656-68. https://doi.org/10.1056/NEJMra022567
  5. Garcia-Cazorla A, De Lonlay P, Nassogne MC, Rustin P, Touati G, Saudubray JM. Long-term follow-up of neonatal mitochondrial cytopathies: a study of 57 patients. Pediatrics 2005;116:1170-7. https://doi.org/10.1542/peds.2004-2407
  6. Bernier FP, Boneh A, Dennett X, Chow CW, Cleary MA, Thorburn DR. Diagnostic criteria for respiratory chain disorders in adults and children. Neurology 2002;59:1406-11. https://doi.org/10.1212/01.WNL.0000033795.17156.00
  7. Wolf NI, Smeitink JA. Mitochondrial disorders: a proposal for consensus diagnostic criteria in infants and children. Neurology 2002;59:1402-5. https://doi.org/10.1212/01.WNL.0000031795.91814.D8
  8. Morava E, van den Heuvel L, Hol F, de Vries MC, Hogeveen M, Rodenburg RJ, et al. Mitochondrial disease criteria: diagnostic applications in children. Neurology 2006;67:1823-6. https://doi.org/10.1212/01.wnl.0000244435.27645.54
  9. Rustin P, Chretien D, Bourgeron T, Gerard B, Rotig A, Saudubray JM, et al. Biochemical and molecular investigations in respiratory chain deficiencies. Clin Chim Acta 1994;228:35-51. https://doi.org/10.1016/0009-8981(94)90055-8
  10. Russell DJ. Gross motor function measure (GMFM-66 & GMFM- 88) users manual. London: Mac Keith, 2002.
  11. Zinn AB. Inborn errors of metabolism. In: Fanaroff AA, Martin RJ, Walsh MC, editors. Fanaroff and Martins neonatal-perinatal medicine: diseases of the fetus and infant. 8th ed. Philadelphia: Mosby Elsevier, 2006:1597-658.
  12. Eng C, Kiuru M, Fernandez MJ, Aaltonen LA. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer 2003;3:193-202. https://doi.org/10.1038/nrc1013
  13. Higuchi M, Kudo T, Suzuki S, Evans TT, Sasaki R, Wada Y, et al. Mitochondrial DNA determines androgen dependence in prostate cancer cell lines. Oncogene 2006;25:1437-45. https://doi.org/10.1038/sj.onc.1209190
  14. Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer 2002;1:9. https://doi.org/10.1186/1476-4598-1-9
  15. Simonnet H, Alazard N, Pfeiffer K, Gallou C, Beroud C, Demont J, et al. Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. Carcinogenesis 2002;23:759-68. https://doi.org/10.1093/carcin/23.5.759
  16. Rustin P, Rotig A. Inborn errors of complex II-- unusual human mitochondrial diseases. Biochim Biophys Acta 2002;1553:117-22. https://doi.org/10.1016/S0005-2728(01)00228-6
  17. Chinnery P, Majamaa K, Turnbull D, Thorburn D. Treatment for mitochondrial disorders. Cochrane Database Syst Rev 2006: CD004426.
  18. Rahman S, Hanna MG. Diagnosis and therapy in neuromuscular disorders: diagnosis and new treatments in mitochondrial diseases. J Neurol Neurosurg Psychiatry 2009;80:943-53. https://doi.org/10.1136/jnnp.2008.158279