Journal of Korean Medical Science

Korean Acad Medical Sciences (대한의학회)
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Complete Recovery of Oxysterol 7α-Hydroxylase Deficiency by Living Donor Transplantation in a 4-Month-Old Infant: the First Korean Case Report and Literature Review

  • Hong, Jeana (Department of Pediatrics, Kangwon National University School of Medicine) ;
  • Oh, Seak Hee (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Nittono, Hiroshi (Junshin Clinic Bile Acid Institute) ;
  • Kimura, Akihiko (Department of Pediatrics and Child Health, Kurume University School of Medicine) ;
  • Kim, Kyung Mo (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
  • Received : 2018.07.16
  • Accepted : 2018.08.30
  • Published : 2018.12.17
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Abstract

Oxysterol $7{\alpha}$-hydroxylase deficiency is a very rare liver disease categorized as inborn errors of bile acid synthesis, caused by CYP7B1 mutations. As it may cause rapid progression to end-stage liver disease even in early infancy, a high index of suspicion is required to prevent fatal outcomes. We describe the case of a 3-month-old boy with progressive cholestatic hepatitis and severe hepatic fibrosis. After excluding other etiologies for his early liver failure, we found that he had profuse urinary excretion of $3{\beta}$-monohydroxy-${\Delta}^5$-bile acid derivatives by gas chromatography/mass spectrometry analysis with dried urine spots on filter paper. He was confirmed to have a compound heterozygous mutation (p.Arg388Ter and p.Tyr469IlefsX5) of the CYP7B1 gene. After undergoing liver transplantation (LT) from his mother at 4 months of age, his deteriorated liver function completely normalized, and he had normal growth and development until the current follow-up at 33 months of age. We report the first Korean case of oxysterol $7{\alpha}$-hydroxylase deficiency in the youngest infant reported to undergo successful living donor LT to date.

Keywords

References

  1. Clayton PT. Disorders of bile acid synthesis. J Inherit Metab Dis 2011;34(3):593-604. https://doi.org/10.1007/s10545-010-9259-3
  2. Craigen WJ. Chapter 160. Disorders of bile acid synthesis. In: Kline MW, editor. Rudolph's Pediatrics, 23rd ed. New York, NY: McGraw-Hill Education; 2018.
  3. Sundaram SS, Bove KE, Lovell MA, Sokol RJ. Mechanisms of disease: inborn errors of bile acid synthesis. Nat Clin Pract Gastroenterol Hepatol 2008;5(8):456-68. https://doi.org/10.1038/ncpgasthep1179
  4. Heubi JE, Setchell KD, Bove KE. Inborn errors of bile acid metabolism. Semin Liver Dis 2007;27(3):282-94. https://doi.org/10.1055/s-2007-985073
  5. Kimura A, Mahara R, Inoue T, Nomura Y, Murai T, Kurosawa T, et al. Profile of urinary bile acids in infants and children: developmental pattern of excretion of unsaturated ketonic bile acids and 7beta-hydroxylated bile acids. Pediatr Res 1999;45(4 Pt 1):603-9. https://doi.org/10.1203/00006450-199904010-00022
  6. Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, et al. Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. Am J Hum Genet 2008;82(2):510-5. https://doi.org/10.1016/j.ajhg.2007.10.001
  7. Wu Z, Martin KO, Javitt NB, Chiang JY. Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1. J Lipid Res 1999;40(12):2195-203.
  8. Stiles AR, McDonald JG, Bauman DR, Russell DW. CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions. J Biol Chem 2009;284(42):28485-9. https://doi.org/10.1074/jbc.R109.042168
  9. Ueki I, Kimura A, Nishiyori A, Chen HL, Takei H, Nittono H, et al. Neonatal cholestatic liver disease in an Asian patient with a homozygous mutation in the oxysterol 7alpha-hydroxylase gene. J Pediatr Gastroenterol Nutr 2008;46(4):465-9. https://doi.org/10.1097/MPG.0b013e31815a9911
  10. Mizuochi T, Kimura A, Suzuki M, Ueki I, Takei H, Nittono H, et al. Successful heterozygous living donor liver transplantation for an oxysterol $7{\alpha}$-hydroxylase deficiency in a Japanese patient. Liver Transpl 2011;17(9):1059-65. https://doi.org/10.1002/lt.22331
  11. Jahnel J, Zohrer E, Fischler B, D'Antiga L, Debray D, Dezsofi A, et al. Attempt to determine the prevalence of two inborn errors of primary bile acid synthesis: results of a European Survey. J Pediatr Gastroenterol Nutr 2017;64(6):864-8. https://doi.org/10.1097/MPG.0000000000001546
  12. Heubi JE, Bove KE, Setchell KD. Oral cholic acid is efficacious and well tolerated in patients with bile acid synthesis and Zellweger spectrum disorders. J Pediatr Gastroenterol Nutr 2017;65(3):321-6. https://doi.org/10.1097/MPG.0000000000001657
  13. Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, et al. Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease. J Clin Invest 1998;102(9):1690-703. https://doi.org/10.1172/JCI2962
  14. Dai D, Mills PB, Footitt E, Gissen P, McClean P, Stahlschmidt J, et al. Liver disease in infancy caused by oxysterol $7{\alpha}$-hydroxylase deficiency: successful treatment with chenodeoxycholic acid. J Inherit Metab Dis 2014;37(5):851-61. https://doi.org/10.1007/s10545-014-9695-6
  15. Kim JS, Kim KM, Oh SH, Kim HJ, Cho JM, Yoo HW, et al. Liver transplantation for metabolic liver disease: experience at a living donor dominant liver transplantation center. Pediatr Gastroenterol Hepatol Nutr 2015;18(1):48-54. https://doi.org/10.5223/pghn.2015.18.1.48
  16. Morioka D, Kasahara M, Takada Y, Corrales JP, Yoshizawa A, Sakamoto S, et al. Living donor liver transplantation for pediatric patients with inheritable metabolic disorders. Am J Transplant 2005;5(11):2754-63. https://doi.org/10.1111/j.1600-6143.2005.01084.x

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