Journal of Inherited Metabolic Disease

, Volume 35, Issue 3, pp 521–530 | Cite as

Bile acid-CoA ligase deficiency—a new inborn error of bile acid metabolism

  • Catherine P. K. Chong
  • Philippa B. Mills
  • Patricia McClean
  • Paul Gissen
  • Christopher Bruce
  • Jens Stahlschmidt
  • A. S. Knisely
  • Peter T. ClaytonEmail author
Original Article


Born at 27 weeks gestation, a child of consanguineous parents of Pakistani origin required prolonged parenteral nutrition. She developed jaundice, with extensive fibrosis and architectural distortion at liver biopsy; jaundice resolved with supportive care. Serum γ-glutamyl transpeptidase values were within normal ranges. The bile acids in her plasma and urine were >85% unconjugated (non-amidated). Two genes encoding bile-acid amidation enzymes were sequenced. No mutations were found in BAAT, encoding bile acid-CoA : aminoacid N-acyl transferase. The patient was homozygous for the missense mutation c.1012C > T in SLC27A5, predicted to alter a highly conserved amino-acid residue (p.H338Y) in bile acid-CoA ligase (BACL). She also was homozygous for the missense mutation c.1772A > G in ABCB11, predicted to alter a highly conserved amino-acid residue (p.N591S) in bile salt export pump (BSEP). BACL is essential for reconjugation of bile acids deconjugated by gut bacteria, and BSEP is essential for hepatocyte-canaliculus export of conjugated bile acids. A female sibling born at term had the same bile-acid phenotype and SLC27A5 genotype, without clinical liver disease. She was heterozygous for the c.1772A > G ABCB11 mutation. This is the first report of a mutation in SLC27A5. The amidation defect may have contributed to cholestatic liver disease in the setting of prematurity, parenteral nutrition, and homozygosity for an ABCB11 mutation.


Bile Acid Cholestasis Cholic Acid Cholestatic Liver Disease Conjugate Bile Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



P.T.C. is funded by Great Ormond Street Children’s Charity. P.G. is funded by a Wellcome Trust Senior Fellowship.


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Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Catherine P. K. Chong
    • 1
  • Philippa B. Mills
    • 1
  • Patricia McClean
    • 2
  • Paul Gissen
    • 1
  • Christopher Bruce
    • 3
  • Jens Stahlschmidt
    • 2
    • 4
  • A. S. Knisely
    • 5
  • Peter T. Clayton
    • 1
    • 6
    Email author
  1. 1.Clinical & Molecular Genetics UnitUCL Institute of Child HealthLondonUK
  2. 2.Leeds Teaching Hospitals NHS TrustLeedsUK
  3. 3.School of Clinical and Experimental MedicineUniversity of BirminghamBirminghamUK
  4. 4.Paediatric HistopathologySt James’s University Hospital Bexley WingLeedsUK
  5. 5.Institute of Liver Studies / HistopathologyKing’s College HospitalLondonUK
  6. 6.Biochemistry Research Group, Clinical & Molecular Genetics UnitUCL Institute of Child HealthLondonUK

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