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Congenital bile acid synthesis defect type 2
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Congenital bile acid synthesis defect type 2

Congenital bile acid synthesis defect type 2 is a rare genetic disorder that impairs bile production, leading to cholestasis, liver damage, and severe fat-soluble vitamin malabsorption in infancy.

Overview

Congenital bile acid synthesis defect type 2 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile from liver cells. Bile is used during digestion to absorb fats and fat-soluble vitamins, such as vitamins A, D, E, and K. People with congenital bile acid synthesis defect type 2 cannot produce (synthesize) bile acids, which are a component of bile that stimulate bile flow and help it absorb fats and fat-soluble vitamins. As a result, an abnormal form of bile is produced.

Symptoms & Clinical Features

The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. If left untreated, the condition typically leads to cirrhosis and death in childhood. Key features include:

  • Failure to gain weight and grow at the expected rate (failure to thrive).
  • Yellowing of the skin and eyes (jaundice) due to impaired bile flow and a buildup of partially formed bile.
  • Excess fat in the feces (steatorrhea).
  • Progressive liver abnormalities, including inflammation or chronic liver disease (cirrhosis).
  • Inability to absorb certain fat-soluble vitamins, which can result in softening and weakening of the bones or problems with blood clotting that lead to prolonged bleeding.

Frequency

The prevalence of congenital bile acid synthesis defect type 2 is unknown. Together, all congenital defects of bile acid synthesis are thought to have a prevalence of 1 to 9 per million people.

Causes

Mutations in the AKR1D1 gene cause congenital bile acid synthesis defect type 2. The AKR1D1 gene provides instructions for making an enzyme called 3-oxo-5-beta(β)-steroid 4-dehydrogenase. This enzyme is found in certain liver cells. Bile acids are produced from cholesterol in a multi-step process. The 3-oxo-5-β-steroid 4-dehydrogenase enzyme is responsible for the third step in that process, which converts 7alpha(α)-hydroxy-4-cholesten-3-one to 7α-hydroxy-5 β-cholesten-3-one.

AKR1D1 gene mutations result in a 3-oxo-5-β-steroid 4-dehydrogenase enzyme with severely reduced function. Without enough functional enzyme, the conversion of 7α-hydroxy-4-cholesten-3-one to 7α-hydroxy-5 β-cholesten-3-one is impaired. The 7α-hydroxy-4-cholesten-3-one instead gets converted into abnormal bile acid compounds that cannot be transported out of the liver into the intestine, where the bile acids are needed to absorb fats and fat-soluble vitamins. As a result, cholesterol and abnormal bile acids build up in the liver and fat-soluble vitamins are not absorbed, which contribute to the signs and

Frequently Asked Questions

Initial clues come from unexplained cholestasis with low serum bile‑acid concentrations and elevated liver enzymes. Definitive diagnosis uses mass‑spectrometry profiling of serum or urine to detect abnormal bile‑acid intermediates, followed by molecular genetic testing of the AKR1D1 gene (the enzyme deficient in type 2).
Transplant is reserved for patients who develop progressive fibrosis or cirrhosis despite optimal bile‑acid replacement, or who experience recurrent liver failure episodes. Eligibility is assessed by pediatric hepatology and transplant teams, with outcomes generally favorable when performed before end‑stage liver disease sets in.
Oral bile‑acid replacement with primary bile acids such as cholic acid (or ursodeoxycholic acid in some protocols) restores the feedback inhibition of toxic intermediates, improves cholestasis, and can halt progression to cirrhosis. Treatment is usually started as soon as the diagnosis is made and continued lifelong, with dose adjustments based on liver function tests.
High‑dose supplementation of vitamins A, D, E, and K is required because absorption remains impaired despite bile‑acid therapy. Vitamin K is given orally or intramuscularly to prevent bleeding, and vitamin D levels are monitored to guide dosing and avoid toxicity. Regular ophthalmologic and bone‑density assessments help detect early complications.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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