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PubMed This is a summary of 49 peer-reviewed journal articles Updated
Pediatric Hepatology

Congenital Bile Acid Synthesis Defect 5 (CBAS5): A Patient Guide

At a Glance

CBAS5 is an inherited ABCD3-related liver disorder that prevents normal bile acid production. Infants may develop jaundice, poor fat and vitamin absorption, and liver injury; diagnosis combines genetic and bile-acid testing, while cholic acid and vitamin support are specialist-directed.

Congenital bile acid synthesis defect 5 (CBAS5) is an ultra-rare, inherited metabolic liver disease that occurs when a child inherits two non-working copies of the ABCD3 gene. This gene is responsible for creating a protein called PMP70, which acts as a biological gatekeeper on the surface of peroxisomes—the tiny “refining centers” inside liver cells [1][2]. Without this gatekeeper, the liver cannot import the building blocks needed to create finished, mature bile acids, leading to a breakdown in the body’s most basic digestive and detoxification processes [3][4].

Because the “refining” process is blocked, the liver begins to accumulate “unfinished” bile acid intermediates known as THCA and DHCA [3]. These intermediates are not just ineffective for digestion; they can be toxic to liver cells, leading to cholestasis (reduced bile flow), jaundice, and potential liver damage over time [5][6]. At the same time, the lack of mature bile acids in the intestines means the body cannot absorb fats or the critical fat-soluble vitamins (A, D, E, and K), which can lead to poor growth, bone weakness, and bleeding risks if not managed aggressively [7][8].

One of the most important aspects of a CBAS5 diagnosis is distinguishing it from more common conditions like biliary atresia. While both cause jaundice and pale stools in infants, biliary atresia is a structural “plumbing” problem, whereas CBAS5 is a metabolic “factory” problem [9][10]. A key clue often found in lab results is that children with CBAS5 may have a normal or surprisingly low GGT level despite being very jaundiced [11][12]. This is a clue that prompts a specialized bile-acid profile, not a result that confirms CBAS5 or excludes biliary atresia. Metabolic testing and urgent surgical evaluation must happen in parallel, and you should never delay a time-sensitive Kasai procedure based on these lab clues [3][10].

While CBAS5 is exceptionally rare, it is managed through a standard of care adapted from broader bile acid disorders. This typically involves bile acid replacement therapy, such as cholic acid, which provides the body with the finished bile acids it lacks and helps “shut off” the production of toxic intermediates [13][14]. Because disease-specific evidence is limited, treatment choice is strictly specialist-directed. When combined with individualized, prescribed vitamin supplementation and regular monitoring by a specialized care team, the goal is to stabilize liver health and support your child’s long-term development and well-being [15][16].

In this guide

6 chapters

01

Understanding Your Child's Diagnosis

Learn what congenital bile acid synthesis defect 5 (CBAS5) means, how ABCD3 variants affect bile acids, and how doctors manage testing and treatment in children.

02

Symptoms and Urgent Warning Signs

Learn about congenital bile acid synthesis defect 5 symptoms and urgent warning signs, including jaundice, pale stools, bleeding, and dehydration in infants.

03

The Biology and Getting the Right Diagnosis

Learn how congenital bile acid synthesis defect 5 (CBAS5) is diagnosed with GGT, THCA/DHCA, ABCD3 genetic testing, and urgent biliary atresia evaluation.

04

Standard of Care Treatment

Learn how congenital bile acid synthesis defect 5 (CBAS5) is treated with cholic acid, vitamin support, monitoring, and when liver transplant may be considered.

05

Building Your Care Team and Preparing for Visits

Learn how to build a CBAS5 care team, prepare for specialist visits, organize genetic and bile acid test reports, and ask about your child's ongoing care.

06

Long-Term Monitoring and Daily Management

Learn how congenital bile acid synthesis defect 5 is monitored, including liver tests, toxic bile acids, vitamin levels, growth, follow-up timing, and red flags.

Common questions in this guide

What causes congenital bile acid synthesis defect 5?
CBAS5 is caused by inheriting two non-working copies of the ABCD3 gene, one from each parent. The gene makes PMP70, a protein that helps liver-cell peroxisomes import materials needed to produce mature bile acids. Without it, unfinished bile acid substances can build up and injure the liver.
How is CBAS5 diagnosed in an infant?
Doctors typically combine genetic testing for ABCD3 with a specialized bile-acid profile, including testing for THCA and DHCA. A normal or low level of the liver enzyme GGT may raise suspicion when jaundice is present, but it does not by itself confirm CBAS5 or rule out biliary atresia. Metabolic testing and evaluation for biliary atresia may need to happen at the same time.
What treatment is used for CBAS5?
Treatment is directed by a specialized liver or metabolic team and may include cholic acid, a replacement bile acid. Cholic acid supplies the finished bile acid the body lacks and may reduce production of harmful intermediates. Prescribed vitamins A, D, E, and K and regular monitoring are also important.
How is CBAS5 different from biliary atresia?
CBAS5 and biliary atresia can both cause jaundice and pale stools in infants, but they are different problems. Biliary atresia involves blocked or abnormal bile ducts, whereas CBAS5 is an inherited problem with bile acid production inside liver cells. A low or normal GGT should not be used to delay urgent evaluation or an indicated Kasai procedure.
Why do children with CBAS5 need vitamin supplements?
Without enough mature bile acids, the intestine cannot absorb fat and vitamins A, D, E, and K effectively. Low vitamin levels can contribute to poor growth, weak bones, and bleeding or bruising. The care team can prescribe supplements and decide how often blood tests are needed.

Get notified when new evidence is published on congenital bile acid synthesis defect 5.

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References

References (16)
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    Substrate Specificity and the Direction of Transport in the ABC Transporters ABCD1-3 and ABCD4.

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    Molecular mechanism of substrate transport by human peroxisomal ABCD3.

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    Bile Acid Synthesis Disorder Masquerading as Intractable Vitamin D-Deficiency Rickets.

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    Congenital Bile Acid Synthesis Defect Type 2 Mimicking Biliary Atresia: A Case Report of Delta-4-3-Oxosteroid 5-Beta-Reductase Deficiency in a Two-Month-Old Infant.

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    [Congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variation in 2 cases and literature review].

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This CBAS5 page is for informational purposes only and does not constitute medical advice. Infant jaundice requires prompt evaluation; follow your child’s liver and metabolic specialists’ instructions about testing and treatment.