Neonatal Medicine

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

DOI QR Code

A Case of Gilbert's Syndrome with Severe Neonatal Hyperbilirubinemia

  • Hong, Ye-Seul (Department of Pediatrics, Soonchunhyang University Hospital) ;
  • Jin, Jang-Yong (Department of Pediatrics, Soonchunhyang University Hospital) ;
  • Lee, Woo-Ryoung (Department of Pediatrics, Soonchunhyang University Hospital)
  • Published : 2010.11.30
⟨ Previous Next ⟩

Abstract

Gilbert's syndrome is caused by a reduction in the activity of uridine diphosphate glucuronosyltransferase (UGT) and induces chronic, non-hemolytic unconjugated hyperbilirubinemia. It has been suggested that 3-10% of the population has Gilbert's syndrome. Commonly, Gilbert's syndrome causes mild symptoms. However, a case of Gilbert's syndrome with severe neonatal hyperbilirubinemia is presented here. The patient developed jaundice three days after birth. Five days after birth, the patient's total serum bilirubin level was 34 mg/dL. The patient received intensive phototherapy and was given oral phenobarbital. Hemolytic hyperbilirubinemia was excluded on the basis of laboratory tests. Heterozygote polymorphisms of the promoter region (-3279T>G) and exon 1 (211G>A) were found in UGT1A1 gene. After discharge, the patient did not require any further treatment. This is the first case of proven Gilbert's syndrome with severe neonatal hyperbilirubinemia in Korea.

Gilbert 증후군(Gilbert's syndrome)은 빌리루빈의 체외배설을 위해 포합시키는 기능을 가진 효소인 uridine diphosphate glucuronosyltransferase (UGT)의 활성도 감소에 의해 야기되며 만성, 비용혈성, 비포합 고빌리루빈혈증을 유발한다. 대부분 경증의 증상을 보이며 인구의 3-10%에서 나타나는 것으로 알려져 있다. 치료로 페노바비탈(phenobarbital)을 투여할 수 있으며 이 페노바비탈은 UGT 효소활성도를 증가시켜 혈중 빌리루빈 농도를 떨어뜨린다. 본 증례에서는 일반적인 경우와 달리 심한 신생아 황달이 동반된 Gilbert 증후군을 기술하였다. 환아는 생후 2-3일경부터 황달 소견을 보였으며 생후 5일경 혈중 총빌리루빈 수치가 34 mg/dL로 높게 상승되어 있어 집중적인 광선치료의 시행과 함께 경구 페노바비탈을 투여 받았다. 검사실 소견에서 정상 혈색소, 망상적혈구 수치 보였으며 direct Coombs' test 에서도 정상 소견 보여 용혈성 고빌리루빈혈증은 제외하였으며 이후 시행한 유전자 검사에서 UGT1A1 유전자의 -3279T>G, 211G>A 변이가 발견되어 Gilbert 증후군으로 진단되었다. 광선치료와 경구 페노바비탈 투여로 혈중 총 빌리루빈 농도의 지속적 감소를 보여 퇴원하였으며 이후 외래검사상 총 빌리루빈 수치는 안정적이었다. 저자들은 심한 신생아 황달을 보인 Gilbert 증후군의 예를 보고하는 바이다.

Keywords

References

  1. Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert's syndrome. N Engl J Med 1995;333:1171-5. https://doi.org/10.1056/NEJM199511023331802
  2. Sugatani J, Yamakawa K, Yoshinari K, Machida T, Takagi H, Mori M, et al. Identification of a defect in the UGT1A1 gene promoter and its association with hyperbilirubinemia. Biochem Biophys Res Commun 2002;292:492-7. https://doi.org/10.1006/bbrc.2002.6683
  3. Kadakol A, Ghosh SS, Sappal BS, Sharma G, Chowdhury JR, Chowdhury NR. Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler- Najjar and Gilbert syndromes: correlation of genotype to phenotype. Hum Mutat 2000;16:297-306. https://doi.org/10.1002/1098-1004(200010)16:4<297::AID-HUMU2>3.0.CO;2-Z
  4. Lim JW, Choi JH, Nam YH, Seo IS, Yoon SM, Koo MS. A case of congenital hemolytic anemia of unknown cause combined with Gilbert's syndrome. Korean J Hematol 2008;43:58-61. https://doi.org/10.5045/kjh.2008.43.1.58
  5. Monaghan G, McLellan A, McGeehan A, Li Volti S, Mollica F, Salemi I, et al. Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. J Pediatr 1999;134:441-6. https://doi.org/10.1016/S0022-3476(99)70201-5
  6. Burchell B, Hume R. Molecular genetic basis of Gilbert's syndrome. J Gastroenterol Hepatol 1999;14:960-6. https://doi.org/10.1046/j.1440-1746.1999.01984.x
  7. Kim YH, Yeon JE, Jung GM, Kim HJ, Kim JS, Byun KS, et al. A study of polymorphism in UDP-glucuronosyltransferase 1 (UGT- 1A1) promoter gene in Korean patients with Gilbert's syndrome. Korean J Hepatol 2002;8:132-8.
  8. Takeuchi K, Kobayashi Y, Tamaki S, Ishihara T, Maruo Y, Araki J, et al. Genetic polymorphisms of bilirubin uridine diphosphateglucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects. J Gastroenterol Hepatol 2004;19:1023-8. https://doi.org/10.1111/j.1440-1746.2004.03370.x
  9. Akaba K, Kimura T, Sasaki A, Tanabe S, Ikegami T, Hashimoto M, et al. Neonatal hyperbilirubinemia and mutation of the bilirubin uridine diphosphate-glucuronosyltransferase gene: a common missense mutation among Japanese, Koreans and Chinese. Biochem Mol Biol Int 1998;46:21-6.
  10. Maruo Y, Topaloglu AK, Takahashi H, Mori A, Iwai M, Duzovali O, et al. Crigler-Najjar syndrome type II caused by a homozygous triple mutation [T-3279G, A(TA)7TAA, and H39D] of UGT1A1. J Pediatr Gastroenterol Nutr 2006;42:236-9. https://doi.org/10.1097/01.mpg.0000184922.09389.0a