Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Inherited metabolic diseases in the urine organic acid analysis of complex febrile seizure patients

복합 열성경련 환자의 소변 유기산 분석에서 나타난 유전대사질환

  • Cheong, Hee Jeong (Department of Pediatrics, College of Medicine, Hallym University Chuncheon Sacred Heart Hospital) ;
  • Kim, Hye Rim (Department of Pediatrics, College of Medicine, Hallym University Chuncheon Sacred Heart Hospital) ;
  • Lee, Seong Soo (Department of Pediatrics, College of Medicine, Hallym University Chuncheon Sacred Heart Hospital) ;
  • Bae, Eun Joo (Department of Pediatrics, College of Medicine, Hallym University Chuncheon Sacred Heart Hospital) ;
  • Park, Won Il (Department of Pediatrics, College of Medicine, Hallym University Chuncheon Sacred Heart Hospital) ;
  • Lee, Hong Jin (Department of Pediatrics, College of Medicine, Hallym University Chuncheon Sacred Heart Hospital) ;
  • Choi, Hui Chul (Department of Neurology, College of Medicine, Hallym University Chuncheon Sacred Heart Hospital)
  • 정희정 (한림대학교 의과대학 소아과학교실) ;
  • 김혜림 (한림대학교 의과대학 소아과학교실) ;
  • 이성수 (한림대학교 의과대학 소아과학교실) ;
  • 배은주 (한림대학교 의과대학 소아과학교실) ;
  • 박원일 (한림대학교 의과대학 소아과학교실) ;
  • 이홍진 (한림대학교 의과대학 소아과학교실) ;
  • 최휘철 (한림대학교 의과대학 신경과학교실)
  • Received : 2008.07.29
  • Accepted : 2008.11.02
  • Published : 2009.02.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : Seizure associated with fever may indicate the presence of underlying inherited metabolic diseases. The present study was performed to investigate the presence of underlying metabolic diseases in patients with complex febrile seizures, using analyses of urine organic acids. Method : We retrospectively analyzed and compared the results of urine organic acid analysis with routine laboratory findings in 278 patients referred for complex febrile seizure. Results : Of 278 patients, 132 had no abnormal laboratory findings, and 146 patients had at least one of the following abnormal laboratory findings: acidosis (n=58), hyperammonemia (n=55), hypoglycemia (n=21), ketosis (n=12). Twenty-six (19.7 %) of the 132 patients with no abnormal findings and 104 (71.2%) of the 146 patients with statistically significant abnormalities showed abnormalities on the organic acid analysis (P<0.05). Mitochondrial respiratory chain disorders (n=23) were the most common diseases found in the normal routine laboratory group, followed by PDH deficiency (n=2) and ketolytic defect (n=1). In the abnormal routine laboratory group, mitochondrial respiratory chain disorder (n=29) was the most common disease, followed by ketolytic defects (n=27), PDH deficiency (n=9), glutaric aciduria type II (n=9), 3-methylglutaconic aciduria type III (n=6), biotinidase deficiency (n=5), propionic acidemia (n=4), methylmalonic acidemia (n=2), 3-hydroxyisobutyric aciduria (n=2), orotic aciduria (n=2), fatty acid oxidation disorders (n=2), 2-methylbranched chain acyl CoA dehydrogenase deficiency (n=2), 3-methylglutaconic aciduria type I (n=1), maple syrup urine disease (n=1), isovaleric acidemia (n=1), HMG-CoA lyase deficiency (n=1), L-2-hydroxyglutaric aciduria (n=1), and pyruvate carboxylase deficiency (n=1). Conclusion : These findings suggest that urine organic acid analysis should be performed in all patients with complex febrile seizure and other risk factors for early detection of inherited metabolic diseases.

목 적 : 발열을 동반한 발작은 소아기에 흔한 문제이며, 단순 열성경련은 간질로 진행되는 경우는 거의 없고 예후가 매우 좋다. 그러나 복합 열성경련과 신경학적인 이상이 동반된 경우, 간질의 가족력이 있는 경우 및 1시간이내의 짧은 발열에 동반된 경우 등은 간질로 진행될 위험이 높고 선천성 대사 질환과 같은 기저 질환이 있을 가능성이 높다. 따라서 본 연구는 복합 열성경련의 환아의 유기산 분석을 통하여 어떠한 대사 질환들이 있는지 알아보고자 시행되었다. 방 법 : 1997년 7월부터 2005년 6월까지의 8년 동안 발작을 주소로 유기산 분석이 의뢰되었던 환아 중에서 복합 열성경련으로 진단되었으며 정맥혈 가스 분석, 암모니아, 간 기능 검사, 소변 검사 등의 통상적인 검사를 시행한 정보가 있었던 278명을 후향적으로 분석하였다. 결 과 : 정보가 있었던 278명의 환자 중에서 기본 검사가 모두 정상인 경우는 132명이었고, 한 가지라도 비정상소견을 보였던 환자는 146명이었다. 가장 흔한 비정상소견은 산혈증으로 58명이었고, 고 암모니아혈증(55명), 저혈당(21명), 케톤산혈증(12명) 등의 순이었다. 통상적인 검사가 정상인 군에서 유기산분석이 비정상소견을 보인 경우는 26명으로 19.7%였으며, 호흡연쇄효소의 이상이 대부분을 차지하였다(23명). 통상적인 검사가 비정상소견을 보였던 146명 중 유기산 분석에서 비정상소견을 보인 경우는 104명으로 71.2%였으며, 통계적으로 의미 있게 높았다(P<0.05). 원인질환으로는 사립체호흡연쇄효소의 이상이 29명, 케톤분해장애가 27명, 피루브산탈수소효소 결핍증과 제2형 글루타르산혈증이 각각 9명의 순이었으며, 제3형 3-메칠글루타콘산혈증 6명, 비오틴분해효소 결핍증 5명, 프로피온산혈증 4명 등이 뒤를 잇고 있으며, 그 외 다양한 질환들이 1-2명씩 진단되었다. 결 론 : 복합 열성경련의 경우에는 정맥혈 가스 분석, 암모니아, 간 기능 검사, 소변 검사 등의 통상적인 검사를 반드시 시행하여야 하며, 비정상소견을 보이는 경우에는 반드시 소변 유기산 분석을 시행하여야 할 것으로 판단된다. 검사소견이 정상일지라도 상당수의 환자에서 호흡연쇄효소의 이상 환자들이 진단되고 있으므로 단순 열성경련이 아니라고 판단된 경우에는 유기산 분석을 시행하여야 된다고 판단된다.

Keywords

References

  1. Fisher RS, van Emde Boas W, Blume, et al. Epileptic seizures and epilepsy. Definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia 2005;46:470-2 https://doi.org/10.1111/j.0013-9580.2005.66104.x
  2. Sadlier LG, Scheffer IE. Febrile seizures. BMJ 2007;334:307- 11 https://doi.org/10.1136/bmj.39087.691817.AE
  3. Offringa M, Bossuyt PM, Lubsen J, Ellenberg JH, Nelson KB, Knudsen FU, et al. Risk factors for seizure recurrence in children with febrile seizures: a pooled analysis of individual patient data from five stdies. J Pediatr 1994;124:574-84 https://doi.org/10.1016/S0022-3476(05)83136-1
  4. Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N Engl J Med 1976; 295:1029-33 https://doi.org/10.1056/NEJM197611042951901
  5. Kjeldsen MJ, Kyvik KO, Friis ML, Christensen K. Genetic and environmental factors in febrile seizures: a Danish population-based twin study. Epilepsy Res 2002;51:167-77 https://doi.org/10.1016/S0920-1211(02)00121-3
  6. Audenaert D, Van Broeckhoven C, De Jonghe P. Genes and loci involved in febrile seizures and related epilepsy syndromes. Hum Mutat 2006;27:391-401 https://doi.org/10.1002/humu.20279
  7. Lee HJ. A clinical approach of inherited metabolic diseases. In: Lee DH editor. Inherited Metabolic diseases: Korea Medical Book Publisher 2008;3-65
  8. Lee HJ. Organic acidemias in Korea. J Korean Pediatr Soc 2002;45:1459-76
  9. Berg AT, Shinnar S. Complex febrile seizures. Epilepsia 1996;37:126-33 https://doi.org/10.1111/j.1528-1157.1996.tb00003.x
  10. Annegers JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Med 1987;316:493-8 https://doi.org/10.1056/NEJM198702263160901
  11. Berg AT, Shinnar S. Unprovoked seizures in children with febrile seizures: short-term outcome. Neurology 1996;47:562- 8
  12. Berg AT, Shinnar S, Darefsky AS, Holford TR, Shapiro ED, Salomon ME, et al. Predictors of recurrent febrile seizures: a prospective cohort study. Arch Pediatr Adolesc Med 1997; 151:371-8 https://doi.org/10.1001/archpedi.1997.02170410045006
  13. Waruiru C, Appleton R. Febrile seizures: an update. Arch Dis Child 2004;89:751-6 https://doi.org/10.1136/adc.2003.028449
  14. Beaudet AL, Scriver CR, Sly WS, Valle D. Genetics, biochemistry, and molecular bases of variant human phenotypes. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:3-128
  15. Brusilow SW, Horwich AL. Urea cycle enzymes. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:1909-64
  16. Cox RP. Errors of lysine metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:1965-70
  17. Chuang DT, Shih VE. Maple syrup urine disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:1971-2006
  18. Sweetman L, Williams JC. Branced chain organic acidurias. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:2125-64
  19. Fenton WA, Gravel RA, Rosenblatt DS. Disorders of propionate and methylmalonate metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:2165-94
  20. Goodman SI, Frerman FE. Organic acidemias due to defects in lysine oxidation: 2-ketoadipic acidemia and glutaric acidemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:2195-204
  21. Munnich A, Roetig A, Cormier-Daire V, Rustin P. Clinical presentation of respiratory chain deficiency. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw- Hill, 2001:2261-74
  22. Mitchelle GA, Fukao T. Inborn errors of ketone body metabolism. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:2327-56
  23. Roe CR, Ding J. Mitochondrial fatty acid oxidation disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:2297-326
  24. Neufeld EF, Muenzer J. The mucopolysaccharidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:3421-52
  25. Beutler E, Grabowsky GA. Gaucher disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:3635-68
  26. von Figura K, gieselman V, Jaeken J. Metachromatic leukodystrophy. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:3695-724
  27. Shoffner JM. Oxidative phosphorylation diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, 2001:2367-425