congenital bile acid synthesis defect 3

Congenital Bile Acid Synthesis Defect Type 3 (CBAS3) Description

Congenital bile acid synthesis defect type 3, also known as CBAS3, is a rare and severe metabolic liver disease. It is characterized by:

• Prolonged jaundice after birth: Infants with CBAS3 often experience prolonged jaundice, which can persist for weeks or even months.
• Hepatomegaly: Enlargement of the liver (hepatomegaly) is a common feature in patients with CBAS3.
• Conjugated hyperbilirubinemia: Elevated levels of conjugated bilirubin in the blood, which can lead to jaundice and other complications.
• Elevations in characteristic abnormal bile acids: Patients with CBAS3 have elevated levels of specific abnormal bile acids in their blood.
• Progressive intrahepatic cholestasis with liver fibrosis: CBAS3 is associated with progressive scarring of the liver (liver fibrosis) and cholestasis, which can lead to cirrhosis.

CBAS3 is an autosomal recessive disorder, meaning that it is inherited in a recessive pattern. It is caused by genetic mutations, also known as pathogenic variants, that affect the enzymes responsible for catalyzing key reactions in bile acid synthesis.

References:

• [2] Congenital bile acid synthesis defect-3 (CBAS3) is an autosomal recessive disorder characterized by prolonged jaundice after birth, hepatomegaly, conjugated hyperbilirubinemia, elevations in characteristic abnormal bile acids, and progressive intrahepatic cholestasis with liver fibrosis (summary by Setchell et al., 1998 and Ueki et al., 2008).
• [12] Congenital bile acid synthesis defect-3 (CBAS3) is an autosomal recessive disorder characterized by prolonged jaundice after birth, hepatomegaly, conjugated hyperbilirubinemia, elevations in characteristic abnormal bile acids, and progressive intrahepatic cholestasis with liver fibrosis (summary by Setchell et al., 1998 and Ueki et al., 2008).
• [13] Congenital bile acid synthesis defect-3 (CBAS3) is an autosomal recessive disorder characterized by prolonged jaundice after birth, hepatomegaly, conjugated hyperbilirubinemia, elevations in characteristic abnormal bile acids, and progressive intrahepatic cholestasis with liver fibrosis.

Common Signs and Symptoms

Congenital bile acid synthesis defect type 3 (CBAS3) is characterized by several distinct signs and symptoms, which can vary in severity and presentation.

• Prolonged Jaundice: Affected individuals often experience prolonged jaundice after birth, which can persist for weeks or even months.
• Hepatomegaly: Enlargement of the liver (hepatomegaly) is a common feature, which can be accompanied by splenomegaly (enlargement of the spleen).
• Conjugated Hyperbilirubinemia: Elevated levels of conjugated bilirubin in the blood are another hallmark of CBAS3.
• Elevations in Abnormal Bile Acids: Characteristic abnormal bile acids are present in elevated amounts, which can contribute to the disease's progression.

Additional Symptoms

Other symptoms associated with CBAS3 include:

• Progressive Intrahepatic Cholestasis: A gradual worsening of liver function, leading to cholestasis (reduced bile flow).
• Liver Fibrosis: Scarring within the liver tissue, which can lead to cirrhosis and further compromise liver function.
• Failure to Thrive: Affected infants may experience failure to gain weight and grow at the expected rate.

References

These symptoms are consistent with descriptions provided in [2], [3], [12], and [13].

Diagnostic Tests for Congenital Bile Acid Synthesis Defect 3

Congenital bile acid synthesis defect type 3 (CBAS3) is a rare genetic disorder that affects the production of bile acids in the liver. Diagnosing CBAS3 can be challenging, but several diagnostic tests can help confirm the condition.

• Molecular Genetic Testing: This test detects mutations in the CYP7B1 gene, which is responsible for encoding the enzyme involved in bile acid synthesis. Molecular genetic testing can confirm a diagnosis of CBAS3 and is available through various clinical genetic testing services [6].
• Liver Function Tests: Liver function tests (LFTs) can help identify abnormalities in liver function, such as elevated levels of conjugated bilirubin, which is characteristic of CBAS3 [7]. However, LFTs alone may not be sufficient to confirm the diagnosis.
• Exome Sequencing: Exome sequencing studies have identified the molecular defects responsible for CBAS3 and can confirm the diagnosis [8].
• Bile Acid Analysis: Bile acid analysis using techniques such as gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) can help identify abnormal bile acids in the blood, which is a hallmark of CBAS3 [12].
• Imaging Studies: Imaging studies, such as ultrasound or magnetic resonance imaging (MRI), may be used to evaluate liver function and detect any abnormalities, such as hepatomegaly or liver fibrosis [9].

Diagnostic Teams

A diagnostic team for congenital bile acid synthesis defect type 3 may include:

• Gastroenterology
• Genetics
• Hepatology

These specialists can work together to diagnose and manage CBAS3.

References: [6] Clinical genetic testing services [7] Liver function tests [8] Exome sequencing studies [9] Imaging studies [12] Bile acid analysis

Treatment Options for Congenital Bile Acid Synthesis Defect Type 3

Congenital bile acid synthesis defect type 3, also known as oxysterol 7α-hydroxylase deficiency, is a rare genetic liver disease that requires prompt and effective treatment to prevent rapid progression to end-stage liver disease.

Ursodeoxycholic Acid Replacement Therapy

According to recent studies [5][6], ursodeoxycholic acid replacement therapy has been shown to be an effective and affordable treatment for congenital bile acid synthesis defect type 3. This treatment involves oral administration of ursodeoxycholic acid, which helps to gradually resolve biochemical and histologic abnormalities, preventing progression to liver failure [9].

Cholic Acid Replacement Therapy

Oral cholic acid replacement has also been shown to be an effective therapy in children with primary bile acid synthesis defects, including congenital bile acid synthesis defect type 3 [8]. This treatment involves oral administration of cholic acid, which helps to stimulate bile flow and limit the production of toxic bile acid precursors through feedback inhibition.

Treatment Goals

The primary goal of treatment for congenital bile acid synthesis defect type 3 is to prevent liver damage and promote overall health. Treatment may involve a combination of medications, including ursodeoxycholic acid or cholic acid replacement therapy, as well as supportive care to manage symptoms and complications [2].

Important Considerations

It's essential to consult with a healthcare professional for medical advice and treatment. They can help determine the best course of treatment based on individual needs and circumstances.

References: [5] by W Mo · 2022 — Ursodeoxycholic acid replacement therapy is an effective and affordable treatment for congenital bile acid synthesis disorder type 3 caused by oxysterol 7α-... [6] Conclusions The patient was successfully treated with ursodeoxycholic acid, which has not been reported previously. Ursodeoxycholic acid replacement therapy is ... [8] by E Gonzales · 2018 · Cited by 51 — Oral cholic acid (CA) replacement has been shown to be an effective therapy in children with primary bile acid synthesis defects, which are rare and severe... [9] Treatment is based on oral administration of cholic acid which leads to gradual resolution of biochemical and histologic abnormalities and prevents progression...

Differential Diagnoses for Congenital Bile Acid Synthesis Defect 3

Congenital bile acid synthesis defect type 3 (CBAS3) is a rare genetic disorder characterized by severe neonatal cholestatic liver disease. When diagnosing CBAS3, it's essential to consider other conditions that may present with similar symptoms.

Similar Conditions:

• **Progressive Familial