Genes Tested:



Congenital bile acid synthesis defect is an autosomal recessive condition associated with neonatal onset liver disease. The impaired production and release of bile acids leads to cholestasis. Bile acid synthesis defects can progress to chronic liver disease, and if left untreated can lead to cirrhosis and death in childhood. Additional symptoms may include failure to thrive, jaundice, fat malabsorption and rickets.


  • Cholestatic jaundice
  • Congenital bile acid synthesis defects (1, 2 & 3)
  • Malabsorption of lipids
  • Alpha-methylacyl-CoA racemase deficiency

Testing Methodology

This test is performed by enrichment of the coding exons, flanking intronic and untranslated regions (5’ and 3’), as well as known pathogenic variants (HGMD 2018.1) in the promoter and deep intronic regions of the genes specified above using oligonucleotide probe hybridization followed by next-generation sequencing with >50X coverage at every target base. All pathogenic and novel variants, as well as variants of unknown (indeterminate) significance, as determined bioinformatically, are confirmed by Sanger sequencing. Regions with <50X will be filled in by Sanger sequencing. A detailed non-coding variant list is available upon request.

Test Sensitivity

The predicted sensitivity of this test is approximately 98% for the detection of nucleotide base changes or homozygous deletions in the coding exons and exon/intron boundaries of the five genes analyzed. Mutations are confirmed by targeted sequencing of the fragment(s) containing the mutation(s). Heterozygous deletions, insertions, genetic recombination events, as well as mutations in regulatory regions or other untranslated regions are not detected by this test. If the patient has received a liver transplant or recent blood transfusion, donor DNA may be present in the blood along with patient DNA (chimerism). In this case, additional testing may be required to rule out chimerism.

Analytical Sensitivity: The sensitivity of DNA sequencing is over 99% for the detection of nucleotide base changes, small deletions and insertions in the regions analyzed.

Limitations: Variants in regulatory regions and non-reported variants in untranslated regions may not be detected by this test. Large deletions involving entire single exons or multiple exons, large insertions and other complex genetic events will not be identified using NGS methodology. Rare primer site variants may lead to erroneous results.

Turnaround Time

28 days

How to Order

Download Heritable Liver Disease requisition. Single gene sequencing and targeted variant analysis is also available for all genes in the Bile Acid Defects Panel.


Cheng, J.B., E. Jacquemin, et al. (2003) "Molecular Genetics of 3beta-Hydroxy-Delta5-C27-Steroid Oxidoreductase Deficiency in 16 Patients with Loss of Bile Acid Synthesis and Liver Disease." The Journal of Clinical Endocrinology and Metabolism 88(4): 1833-41.

Drury, Jason E., Rebekka Mindnich, and Trevor M. Penning. “Characterization of Disease-Related 5beta-Reductase (AKR1D1) Mutations Reveals Their Potential to Cause Bile Acid Deficiency.” The Journal of Biological Chemistry 285, no. 32 (August 6, 2010): 24529–37. doi:10.1074/jbc.M110.127779.

Ferdinandusse, S., G. Jimenez-Sanchez, et al. (2014) “A Novel Bile Acid Biosynthesis Defect due to a Deficiency of Peroxisomal ABCD3.” Human molecular genetics, 24(2), 361-370.

Lemonde, H.A., E.J. Custard, et al. (2003) "Mutations in SRD5B1 (AKR1D1), the Gene Encoding delta(4)-3-Oxosteroid 5beta-Reductase, in Hepatitis and Liver Failure in Infancy." Gut 52(10): 1494-9.

Setchell, K.D., M. Schwarz, et al. (1998) "Identification of a New Inborn Error in Bile Acid Synthesis: Mutation of the Oxysterol 7alpha-Hydroxylase Gene Causes Severe Neonatal Liver Disease." The Journal of Clinical Investigation 102(9): 1690-703.

van Mil, S.W.C., R.H.J. Houwen, et al. (2005) "Genetics of Familial Intrahepatic Cholestasis Syndromes." Journal of Medical Genetics 42(6): 449-63.