Identification of a new inborn error in bile acid synthesis: Mutation of the oxysterol 7α-hydroxylase gene causes severe neonatal liver disease

Journal of Clinical Investigation

Volumn 102, Issue 9, 1998, Pages 1690-1703

  Setchell, Kenneth D R ^a   Schwarz, Margrit ^b   O'Connell, Nancy C ^a   Lund, Erik G ^b   Davis, Daphne L ^b   Lathe, Richard ^c   Thompson, Henry R ^d   Tyson, R Weslie ^d   Sokol, Ronald J ^d   Russell, David W ^b  

^a CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS AT DALLAS   (United States)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d CHILDREN S HOSPITAL   (United States)

Author keywords

Cholestasis; Cholesterol metabolism; Genetics; Mass spectrometry

Indexed keywords

26 HYDROXYCHOLESTEROL; 3BETA HYDROXY 5 CHOLESTENOIC ACID; 3BETA HYDROXYCHOL 5 ENOIC ACID; BILE ACID; OXYGENASE; OXYSTEROL 7ALPHA HYDROXYLASE; UNCLASSIFIED DRUG;

ARTICLE; BILE ACID SYNTHESIS; CASE REPORT; ENZYME DEFICIENCY; GAS CHROMATOGRAPHY; GENE MUTATION; HUMAN; HYDROXYLATION; INBORN ERROR OF METABOLISM; INFANT; INTRAHEPATIC CHOLESTASIS; LIVER CIRRHOSIS; LIVER FAILURE; LIVER MICROSOME; MALE; MASS SPECTROMETRY; NEWBORN DISEASE; PRIORITY JOURNAL;

EID: 0032211865     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI2962     Document Type: Article

References (87)

1. Setchell, K.D.R., and N.C. O'Connell. 1994. Inborn errors of bile acid metabolism. In Liver Disease in Children. F.J. Suchy, editor. Mosby-Yearbook, Inc., St. Louis, MO. 835-851.
2. Setchell, K.D.R. 1996. Disorders of bile acid synthesis and metabolism. In Pediatric Gastrointestinal Disease. Pathophysiology, Diagnosis, Management. W.A. Walker, P.R. Durie, J.R. Hamilton, J.A. Walker-Smith, and J.A. Watkins, editors. B.C. Decker Inc., Toronto/Philadelphia. 1205-1233.
3. Clayton, P.T., J.V. Leonard, A.M. Lawson, K.D.R. Setchell, S. Andersson, B. Egestad, and J. Sjovall. 1987. Familial giant cell hepatitis associated with synthesis of 3β,7α-dihydroxy-and 3β,7α,12α-trihydroxy-5-cholenoic acids. J. Clin. Invest. 79:1031-1038.
4. 4-3-Oxosteroid 5β-reductase deficiency described in identical twins with neonatal hepatitis. A new inborn error in bile acid synthesis. J. Clin. Invest. 82:2148-2157.
5. Setoguchi, T., G. Salen, G.S. Tint, and E.H. Mosbach. 1974. A biochemical abnormality in cerebrotendinous xanthomatosis. Impairment of bile acid biosynthesis associated with incomplete degradation of the cholesterol side chain. J. Clin. Invest. 53:1393-1401.
6. Setchell, K.D.R., P. Bragetti, L. Zimmer-Nechemias, C. Daugherty, M.A. Pelli, R. Vaccaro, G. Gentilli, E. Distrutti, G. Dozzini, A. Morelli, and C. Clerici. 1992. Oral bile acid treatment and the patient with Zellweger syndrome. Hepatology. 15:198-207.
7. Clayton, P.T., M. Casteels, G. Mieli-Vergani, and A.M. Lawson. 1995. Familial giant cell hepatitis with low bile acid concentrations and increased urinary excretion of specific bile alcohols: a new inborn error of bile acid synthesis? Pediatr. Res. 37:424-431.
8. 27 bile acids but normal fibroblast branched-chain fatty acid oxidation. J. Inherit. Metab. Dis. 19:761-768.
9. Setchell, K.D.R., J.E. Heubi, N.C. O'Connell, A.F. Hofmann, and J. Lavine. 1997. Identification of a unique inborn error in bile acid conjugation involving a deficiency in amidation. In Bile Acids in Hepatobiliary Disease: Basic and Clinical Applications. G. Paumgartner, A. Stiehl, and W. Gerok, editors. Kluwer Academic Publications, Dordrecht/Boston/London. 43-47.
10. Russell, D.W., and K.D.R. Setchell. 1992. Bile acid biosynthesis. Biochemistry. 31:4737-4739.
11. 4-3-oxosteroid 5β-reductase deficiency). Hepatology. 18:1096-1101.
12. 27-steroid dehydrogenase deficiency with chenodeoxycholic acid. Arch. Dis. Child. 65:1121-1124.
13. Setchell, K.D.R., and J.M. Street. 1987. Inborn errors of bile acid synthesis. Semin. Liver Dis. 7:85-99.
14. Axelson, M., and J. Sjovall. 1990. Potential bile acid precursors in plasma: possible indicators of biosynthetic pathways to cholic and chenodeoxycholic acids in man. J. Steroid Biochem. 36:631-640.
15. Axelson, M., J. Shoda, J. Sjovall, A. Toll, and K. Wikvall. 1992. Cholesterol is converted to 7α-hydroxy-3-oxo-4-cholestenoic acid in liver mitochondria. Evidence for a mitochondrial sterol 7α-hydroxylase. J. Biol. Chem. 267: 1701-1704.
16. Toll, A., J. Shoda, M. Axelson, J. Sjovall, and K. Wikvall. 1992. 7α-Hydroxylation of 26-hydroxycholesterol, 3β-hydroxy-5-cholestenoic acid and 3β-hydroxy-5-cholenoic acid by cytochrome P-450 in pig liver microsomes. FEBS Lett. 296:73-76.
17. Martin, K.O., K. Budai, and N.B. Javitt. 1993. Cholesterol and 27-hydroxycholesterol 7α-hydroxylation: evidence for two different enzymes. J. Lipid Res. 34:581-588.
18. Shoda, J., A. Toll, M. Axelson, F. Pieper, K. Wikvall, and J. Sjovall. 1993. Formation of 7α-and 7β-hydroxylated bile acid precursors from 27-hydroxycholesterol in human liver microsomes and mitochondria. Hepatology. 17:395-403.
19. Javitt, N.B. 1994. Bile acid synthesis from cholesterol: regulatory and auxiliary pathways. FASEB (Fed. Am. Soc. Exp. Biol.) J. 8:1308-1311.
20. Vlahcevic, Z.R., R.T. Stravitz, D.M. Heuman, P.B. Hylemon, and W.M. Pandak. 1997. Quantitative estimations of the contribution of different bile acid pathways to total bile acid synthesis in the rat. Gastroenterology. 113:949-957.
21. Schwarz, M., E.G. Lund, K.D.R. Setchell, H.J. Kayden, J.E. Zerwekh, I. Bjorkhem, J. Herz, and D.W. Russell. 1996. Disruption of cholesterol 7α-hydroxylase gene in mice. J. Biol. Chem. 271:18024-18031.
22. Schwarz, M., E.G. Lund, R. Lathe, I. Bjorkhem, and D.W. Russell. 1997. Identification and characterization of a mouse oxysterol 7α-hydroxylase cDNA. J. Biol. Chem. 272:23995-24001.
23. Setchell, K.D.R., and A. Matsui. 1983. Serum bile acid analysis: the application of liquid-gel Chromatographic techniques and capillary column gas chromatography and mass spectrometry. Clin. Chim. Acta. 127:1-17.
24. Setchell, K.D.R., D. Kritchevsky, and P.P. Nair. 1988. The Bile Acids. Chemistry, Physiology and Metabolism. Volume 4: Methods and Applications. Plenum Press, New York/London. 582 pp.
25. Setchell, K.D.R., and A.M. Lawson. 1989. Bile acids. In Mass Spectrometry. A.M. Lawson, editor. Walter deGruyter, Berlin/New York. 55-125.
26. Setchell, K.D.R., and J. Worthington. 1982. A rapid method for the quantitative extraction of bile acids and their conjugates from serum using commercially available reverse-phase octadecylsilane bonded silica cartridges. Clin. Chim. Acta. 125:135-144.
27. Rodrigues, C.M.P., and K.D.R. Setchell. 1996. Performance characteristics of reverse-phase bonded silica cartridges for serum bile acid extraction. Biomed. Chromatogr. 10:1-5.
28. Setchell, K.D.R., A.M. Lawson, N. Tanida, and J. Sjovall. 1983. General methods for the analysis of metabolic profiles of bile acids and related compounds in feces. J. Lipid Res. 24:1085-1100.
29. Hirano, Y., H. Miyazaki, S. Higashidate, and F. Nakayama. 1987. Analysis of 3-sulfated and nonsulfated bile acids by one-step hydrolysis and high performance liquid chromatography. J. Lipid Res. 28:1524-1529.
30. Nair, P.P., and C.C. Garcia. 1969. A modified gas-liquid Chromatographic procedure for the rapid determination of bile acids in biological fluids. Anal. Biochem. 29:164-166.
31. Alme, B., A. Bremmelgaard, J. Sjovall, and P. Thomassen. 1977. Analysis of metabolic profiles of bile acids in urine using a lipophilic anion exchanger and computerized gas-liquid chromatography-mass spectrometry. J. Lipid Res. 18:339-362.
32. Blau, K., and G.S. King. 1979. Handbook of Derivatives for Chromatography. Heyden & Son Ltd., London/Philadelphia/Rheine. 576 pp.
33. Lawson, A.M., and K.D.R. Setchell. 1988. Mass spectrometry of bile acids. In The Bile Acids. Volume 4: Methods and Applications. K.D.R. Setchell, D. Kritchevsky, and P.P. Nair, editors. Plenum Press, New York. 167-267.
34. Setchell, K.D.R. 1983. Liquid-solid extraction, lipophilic gel chromatography and capillary column gas chromatography in the analysis of bile acids from biological samples. In Bile Acids in Gastroenterology. L. Barbara, R.H. Dowling, A.F. Hofmann, and E. Roda, editors. MTP Press Ltd., Lancaster/Boston/The Hague. 1-18.
35. Makino, I., J. Sjovall, A. Norman, and B. Strandvik. 1971. Excretion of 3β-hydroxy-5-cholenoic and 3α-hydroxy-5α-cholanoic acids in urine of infants with biliary atresia. FEBS Lett. 15:161-164.
36. 19 steroids. Org. Mass Spectrom. 7:925-948.
37. 5-steroids. Org. Mass Spectrom. 7: 277-281.
38. 29 dicarboxylic acid as a major component of their serum. Eur. J. Biochem. 102:173-183.
39. Axelson, M., B. Mork, and J. Sjovall. 1988. Occurrence of 3β-hydroxy-5-cholestenoic acid, 3β,7α-dihydroxy-5-cholestenoic, and 7α-hydroxy-3-oxo-4-cholestenoic acid as normal constituents in human blood. J. Lipid Res. 29: 629-641.
40. Gustafsson, J.-A., and J. Sjovall. 1969. Identification of 22-, 24-and 26-hydroxycholesterol in the steroid sulphate fraction of faeces from infants. Eur. J. Biochem. 8:467-472.
41. Lund, E., I. Bjorkhem, C. Furster, and K. Wikvall. 1993. 24-, 25-and 27-hydroxylation of cholesterol by a purified preparation of 27-hydroxylase from pig liver. Biochim. Biophys. Acta. 1166:177-182.
42. Bergstrom, S., and H. Danielsson. 1958. On the regulation of the bile acid formation in the rat liver. Acta Physiol. Scand. 43:1-7.
43. Shefer, S., S. Hauser, I. Bekersky, and E.H. Mosbach. 1969. Feedback regulation of bile acid biosynthesis in the rat. J. Lipid Res. 10:404-411.
44. Danielsson, H. 1973. Influence of dietary bile acids on formation of bile acids in rat. Steroids. 22:667-676.
45. 27-sterols in human fetal liver. J. Lipid Res. 27:801-806.
46. Cohen, J.C., J.J. Cali, D.F. Jelinek, M. Mehrabian, R.S. Sparkes, A.J. Lusis, D.W. Russell, and H.H. Hobbs. 1992. Cloning of the human cholesterol 7α-hydroxylase gene (CYP7) and localization to chromosome 8q11-q12. Genomics. 14:153-161.
47. Stapleton, G., M. Steel, M. Richardson, J.O. Mason, K.A. Rose, R.G.M. Morris, and R. Lathe. 1995. A novel cytochrome P450 expressed primarily in brain. J. Biol. Chem. 270:29739-29745.
48. Myant, N.B., and K.A. Mitropoulos. 1977. Cholesterol 7α-hydroxylase. J. Lipid Res. 18:135-153.
49. Zhang, J., O. Larsson, and J. Sjovall. 1995. 7α-Hydroxylation of 25-hydroxycholesterol and 27-hydroxycholesterol in human fibroblasts. Biochim. Biophys. Acta. 1256:353-359.
50. Zhang, J., Y. Akwa, E.-E. Baulieu, and J. Sjovall. 1995. 7α-Hydroxylation of 27-hydroxycholesterol in rat brain microsomes. C.R. Acad. Sci. Paris. 318:345-349.
51. Reiss, A.B., K.O. Martin, D.E. Rojer, S. Iyer, E.A. Grossi, A.C. Galloway, and N.B. Javitt. 1997. Sterol 27-hydroxylase: expression in human arterial endothelium. J. Lipid Res. 38:1254-1260.
52. Axelson, M., O. Larsson, J. Zhang, J. Shoda, and J. Sjovall. 1995. Structural specificity in the suppression of HMG-CoA reductase in human fibroblasts by intermediates in bile acid biosynthesis. J. Lipid Res. 36:290-298.
53. Martin, K.O., A.B. Reiss, R. Lathe, and N.B. Javitt. 1997. 7α-Hydroxylation of 27-hydroxycholesterol: biologic role in the regulation of cholesterol synthesis. J. Lipid Res. 38:1053-1058.
54. Vlahcevic, Z.R., P. Juttijudata, C.C. Bell, Jr., and L. Swell. 1972. Bile acid metabolism in patients with cirrhosis. II. Cholic and chenodeoxycholic acid metabolism. Gastroenterology. 62:1174-1181.
55. McCormick, W.C., C.C. Bell, Jr., L. Swell, and Z.R. Vlahcevic. 1973. Cholic acid synthesis as an index of the severity of liver disease in man. Gut. 14: 895-902.
56. Stiehl, A., D.L. Earnest, and W.H. Admirand. 1975. Sulfation and renal excretion of bile salts in patients with cirrhosis of the liver. Gastroenterology. 68:534-544.
57. Engelking, L.R., S. Barnes, B.I. Hirschowitz, C.A. Dasher, J.G. Spenney, and D. Naftel. 1980. Determination of the pool size and synthesis rate of bile acids by measurements in blood of patients with liver disease. Clin. Sci. 58: 485-492.
58. Axelson, M., B. Mork, A. Aly, O. Wisen, and J. Sjovall. 1989. Concentrations of cholestenoic acids in plasma from patients with liver disease. J. Lipid Res. 30:1877-1882.
59. Setchell, K.D.R., D.A. Piccoli, N.C. O'Connell, E. Jacquemin, and O. Bernard. 1993. Progressive intrahepatic cholestasis with normal γ-glutamyl-transferase is highly associated with the 3β-hydroxysteroid dehydrogenase/ isomerase deficiency, an inborn error in bile acid synthesis: a new category of metabolic liver disease. Hepatology. 18:178A. (Abstr.)
60. Clayton, R.J., F.L. Iber, B.H. Ruebner, and V.A. McKusick. 1969. Byler disease. Fatal familial intrahepatic cholestasis in an Amish kindred. Am. J. Dis. Child. 117:112-124.
61. Maggiore, G., O. Bernard, C.A. Reily, M. Hadchouel, A. Lemonnier, and D. Alagille. 1987. Normal serum γ-glutamyl-transpeptidase activity identifies groups of infants with idiopathic cholestasis with poor prognosis. J. Pediatr. 111:251-252.
62. Whitington, P.F., D.K. Freese, E.M. Alonso, S.J. Schwarzenberg, and H.L. Sharp. 1994. Clinical and biochemical findings in progressive familial intrahepatic cholestasis. J. Pediatr. Gastroenterol. Nutr. 18:134-141.
63. Witzleben, C.L., D.A. Piccoli, and K.D.R. Setchell. 1992. A new category of causes of intrahepatic cholestasis. J. Pediatr. Path. 12:269-274.]
64. Hoshita, T. 1985. Bile alcohols and primative bile acids. In Sterols and Bile Acids. H. Danielsson and J. Sjovall, editors. Elsevier Science Publishers BV, Amsterdam. 279-302.
65. Takikawa, H., H. Otsuka, T. Beppu, and Y. Seyama. 1985. Determination of 3β-hydroxy-5-cholenoic acid in serum of hepatobiliary diseases: its glucuronidated and sulfated conjugates. Biochem. Med. 33:393-400.
66. Deleze, G., G. Paumgartner, G. Karlaganis, W. Giger, M. Reinhard, and D. Sidiropoulos. 1978. Bile acid pattern in human amniotic fluid. Eur. J. Clin. Invest. 8:41-45.
67. Nakagawa, M., and K.D.R. Setchell. 1990. Bile acid metabolism in early life: studies of amniotic fluid. J. Lipid Res. 31:1089-1098.
68. Back, P., and K. Ross. 1973. Identification of 3β-hydroxy-5-cholenoic acid in human meconium. Hoppe-Seyler's Z. Physiol. Chem. 354:83-89.
69. Javitt, N.B., E. Kok, M. Gut, I. Rajagopalan, and K. Budai. 1984. Neonatal cholestasis: identification of a metabolic error in bile acid synthesis. Pediatr. Res. 18(Suppl.):200A. (Abstr.)
70. Javitt, N.B., and S. Emerman. 1968. Effect of sodium taurolithocholate on bile flow and bile excretion. J. Clin. Invest. 47:1002-1014.
71. Steiger, B., J. Zhang, B. O'Neill, J. Sjovall, and P.J. Meier. 1997. Differential interaction of bile acids from patients with inborn errors of bile acid synthesis with hepatocellular bile acid transporters. Eur. J. Biochem. 244:39-44.
72. Mathis, U., G. Karlaganis, and R. Preisig. 1983. Monohydroxy bile salt sulfates: tauro-3β-hydroxy-5-cholenoate-3-sulfate induces intrahepatic cholestasis in rats. Gastroenterology. 85:674-681.
73. Sokol, R.J., M.W. Devereaux, R.A. Khandwala, and K. O'Brien. 1993. Evidence for involvement of oxygen free radicals in bile acid toxicity to isolated rat hepatocytes. Hepatology. 17:869-881.
74. Hall, R., E. Kok, and N.B. Javitt. 1988. Bile acid synthesis: down-regulation by monohydroxy bile acids. FASEB (Fed. Am. Soc. Exp. Biol.) J. 2:152-156.
75. Javitt, N.B., E. Kok, S. Burstein, B. Cohen, and J. Kutscher. 1981. 26-Hydroxycholesterol. Identification and quantitation in human serum. J. Biol. Chem. 256:12644-12646.
76. Koopman, B.J., J.C. Van Der Molen, B.G. Wolthers, and J.B. Vanderpas. 1987. Determination of some hydroxy-cholesterols in human serum samples. J. Chromatogr. 416:1-13.
77. van Doormaal, J.J., N. Smit, B.J. Koopman, J.C. van der Molen, B.G. Woolthers, and H. Doorenbos. 1989. Hydraxycholesterols in serum from hypercholesterolaemic patients with and without bile acid sequestrant therapy. Clin. Chim. Acta. 181:273-280.
78. Harik-Khan, R., and R.P. Holmes. 1990. Estimation of 26-hydroxycholesterol in serum by high-performance liquid chromatography and its measurement in patients with atherosclerosis. J. Steroid Biochem. 36:351-355.
79. Dzeletovic, S., O. Breuer, E. Lund, and U. Diczfalusy. 1995. Determination of cholesterol oxidation products in human plasma by isotope dilutionmass spectrometry. Anal. Biochem. 225:73-80.
80. Javitt, N.B., E. Kok, F. Carubbi, T. Blizzard, M. Gut, and C.Y. Byon. 1986. Bile acid biosynthesis. Metabolism of 3β-hydroxy-5-cholenoic acid to chenodeoxycholic acid. J. Biol. Chem. 261:12486-12489.
81. Lee, C., K. Martin, and N.B. Javitt. 1996. Bile acid synthesis: 7α-hydroxylation of intermediates in the sterol 27-hydroxylase metabolic pathway. J. Lipid Res. 37:1356-1362.
82. Setchell, K.D.R., C.M.P. Rodrigues, C. Clerici, A. Solinas, A. Morrelli, C. Gartung, and J. Boyer. 1997. Bile acid concentrations in human and rat liver tissue and in hepatocyte nuclei. Gastroenterology. 112:226-235.
83. Colombo, C., G. Zuliani, M. Ronchi, J. Breidenstein, and K.D.R. Setchell. 1987. Biliary bile acid composition of the human fetus in early gestation. Pediatr. Res. 21:197-200.
84. Setchell, K.D.R., R. Dumaswala, C. Colombo, and M. Ronchi. 1988. Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile. J. Biol. Chem. 263:16637-16644.
85. Collins, J.C., R.P. Altman, K.O. Martin, and N.B. Javitt. 1994. Bile acid synthesis in fetal and neonatal life: expression of cholesterol 7α-hydroxylase and 27-hydroxycholesterol-7α-hydroxylase activities. Pediatr. Res. 35:126A. (Abstr.)
86. Hasemann, C.A., R.G. Kurumbail, S.S. Boddupalli, J.A. Peterson, and J. Deisenhofer. 1995. Structure and function of cytochromes P450: a comparative analysis of three crystal structures. Structure. 3:41-62.
87. Zhang, J., A. Dricu, and J. Sjovall. 1997. Studies on the relationships between 7α-hydroxylation and the ability of 25-and 27-hydroxycholesterol to suppress the activity of HMG-CoA reductase. Biochim. Biophys. Acta. 1344:241-249.