Congenital bile acid synthesis defect type 2

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What is congenital bile acid synthesis defect type 2?

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.

The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. Affected infants usually have a failure to gain weight and grow at the expected rate (failure to thrive) and 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) is another feature of congenital bile acid synthesis defect type 2. As the condition progresses, affected individuals can develop liver abnormalities including inflammation or chronic liver disease (cirrhosis). Some individuals with congenital bile acid synthesis defect type 2 cannot absorb certain fat-soluble vitamins, which can result in softening and weakening of the bones (rickets) or problems with blood clotting that lead to prolonged bleeding.

If left untreated, congenital bile acid synthesis defect type 2 typically leads to cirrhosis and death in childhood.

How common is congenital bile acid synthesis defect type 2?

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.

What genes are related to congenital bile acid synthesis defect type 2?

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 that produce bile acids. 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 symptoms of congenital bile acid synthesis defect type 2.

How do people inherit congenital bile acid synthesis defect type 2?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of congenital bile acid synthesis defect type 2?

These resources address the diagnosis or management of congenital bile acid synthesis defect type 2 and may include treatment providers.

You might also find information on the diagnosis or management of congenital bile acid synthesis defect type 2 in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about congenital bile acid synthesis defect type 2?

You may find the following resources about congenital bile acid synthesis defect type 2 helpful. These materials are written for the general public.

MedlinePlus - Health information (4 links)
Additional NIH Resources - National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases: Cirrhosis
Educational resources - Information pages (5 links)
Patient support - For patients and families (6 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

Genetic Testing Registry - Repository of genetic test information (1 link)
ClinicalTrials.gov - Linking patients to medical research
PubMed - Recent literature
OMIM - Genetic disorder catalog

What other names do people use for congenital bile acid synthesis defect type 2?

CBAS2
cholestasis with delta(4)-3-oxosteroid 5-beta-reductase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about congenital bile acid synthesis defect type 2?

Ask the Genetic and Rare Diseases Information Center

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

What glossary definitions help with understanding congenital bile acid synthesis defect type 2?

acids ; autosomal ; autosomal recessive ; bile ; blood clotting ; cell ; cholesterol ; chronic ; cirrhosis ;clotting ; congenital ; deficiency ; dehydrogenase ; digestion ; digestive ; enzyme ; failure to thrive ;feces ; gene ; inflammation ; inherited ; intestine ; jaundice ; prevalence ; recessive ; rickets ; soluble ;steatorrhea ; synthesis ; vitamins

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

References (3 links)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook