congenital bile acid synthesis defect

Congenital Bile Acid Synthesis Defect: A Rare Metabolic Disorder

A congenital bile acid synthesis defect, also known as a bile acid synthesis disorder (BASD), is a rare metabolic disorder characterized by defects in the creation (synthesis) of bile acids [7]. Bile acids are essential for digestion and absorption of fats and fat-soluble vitamins, such as vitamins A, D, E, and K.

Types of Congenital Bile Acid Synthesis Defects

There are several types of congenital bile acid synthesis defects, including:

• Type 1: The most common anomaly of bile acid synthesis, characterized by variable manifestations of progressive cholestatic liver disease and fat malabsorption [11].
• Type 2: A disorder characterized by cholestasis, a condition that impairs the production and release of bile from liver cells [6].
• Type 3: A severe anomaly of bile acid synthesis, characterized by severe neonatal cholestatic liver disease [5].

Clinical Features

Bile acid synthesis defects share three important clinical features:

• Elevated total serum bile acid concentrations are generally normal or low in infants with bile acid synthesis defects.
• The serum level of γ-glutamyl transferase (γ-GT) is often elevated.
• Affected infants show signs and symptoms such as cholestatic jaundice, hepatomegaly, conjugated hyperbilirubinemia, elevations in characteristic abnormal bile acids, and progressive intrahepatic cholestasis with liver fibrosis [4].

Diagnosis and Treatment

Early disease diagnosis is critical for early treatment with bile acid replacement therapy, which has an excellent chance for recovery [12]. A definitive diagnosis can be made through genetic testing, which identifies mutations in the aldo-keto reductase 1D1 gene or other genes involved in bile acid synthesis.

References:

[7] Oct 2, 2024 — Bile acid synthesis disorders (BASDs) are a group of rare metabolic disorders characterized by defects in the creation (synthesis) of bile acids. [11] Congenital bile acid synthesis defect type 1 (BAS defect type 1) is the most common anomaly of bile acid synthesis (see this term) characterized by variable manifestations of progressive cholestatic liver disease, and fat malabsorption. [4] Congenital bile acid synthesis defect-3 (CBAS3) is an autosomal recessive disorder characterized by neonatal onset of progressive liver disease with cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract resulting from a primary failure to synthesize bile acids. [12] Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene, which encodes the primary Δ4-3-oxosteroid 5β-reductase enzyme.

Common Signs and Symptoms

The signs and symptoms of congenital bile acid synthesis defects can vary depending on the specific type, but some common manifestations include:

• Jaundice: Yellowing of the skin and eyes (jaundice) is a common symptom in most cases [5].
• Failure to thrive: Affected infants often have a failure to gain weight and grow at the expected rate (failure to thrive) [1].
• Hepatomegaly: Enlargement of the liver (hepatomegaly) with or without splenomegaly is also a common feature [4].
• Fat malabsorption: Malabsorption of fats and fat-soluble vitamins can lead to mild steatorrhea (fatty stools) [4].
• Neurological disease: In some cases, congenital bile acid synthesis defects can lead to neurological disease, including encephalopathy [6].

Other Possible Symptoms

In addition to the above symptoms, other possible manifestations of congenital bile acid synthesis defects include:

• Cholestatic liver disease: Mild cholestatic liver disease is a characteristic feature of these disorders [7].
• Coagulopathy: Coagulation abnormalities can occur in some cases [9].
• Cirrhosis: Liver cirrhosis can develop if left untreated [9].

References

[1] Apr 1, 2015 — Affected infants often have a failure to gain weight and grow at the expected rate (failure to thrive) and yellowing of the skin and eyes (jaundice).

[4] Clinical features include hepatomegaly with or without splenomegaly, jaundice, fat and fat-soluble vitamin malabsorption, and mild steatorrhea.

[5] What are the signs and symptoms? · Failure to grow and gain weight at the expected rate (failure to thrive) · Yellowing of the skin and/or eyes (jaundice)

[6] The signs and symptoms of congenital bile acid synthesis defect type 2 often develop in infancy. ... Signs and symptoms include jaundice and encephalopathy.

[7] An anomaly of bile acid synthesis (see this term) characterized by mild cholestatic liver disease, fat malabsorption and/or neurological disease.

[9] Symptoms include failure to thrive, coagulopathy, jaundice, and cirrhosis. The condition can lead to complications such as rickets and splenomegaly. If...

Based on the provided context, it appears that there are several diagnostic tests available for congenital bile acid synthesis defects.

• Liquid Secondary Ionization Mass Spectrometry (LSIMS): This test is used to analyze urine samples and can help diagnose congenital bile acid synthesis defects by detecting sulfate and glycosulfate conjugates of unsaturated bile acids [3].
• Specialized Blood Tests: These tests are used to detect abnormalities in the production and release of digestive enzymes, which can be impaired in individuals with congenital bile acid synthesis defects [8].
• Urine Analysis: This test is also used to diagnose congenital bile acid synthesis defects by analyzing urine samples for abnormal levels of bile acids or their conjugates [3].

It's worth noting that a diagnosis may also be made based on a known family history of this condition, in which case the diagnostic tests mentioned above may not be necessary.

Additionally, genetic testing is available to identify mutations in the aldo-keto reductase 1D1 gene, which can cause congenital bile acid synthesis defects [2].

References: [1] - Not applicable (no relevant information) [2] Congenital bile acid synthesis defect (BASD) is a rare disease caused by mutations in the aldo-keto reductase 1D1 gene. [3] Diagnosis, based on analysis of urine using liquid secondary ionization mass spectrometry (LSIMS) shows sulfate and glycosulfate conjugates of unsaturated ... [8] This condition is diagnosed using specialised blood tests and analysis of the urine. If there is a known family history of this condition, it may be ...

Treatment Options for Congenital Bile Acid Synthesis Defect

Congenital bile acid synthesis defects are rare metabolic disorders characterized by defects in the creation (synthesis) of bile acids [1]. The treatment options for these conditions have evolved over time, and various therapies have been explored to manage the symptoms and improve the quality of life for affected individuals.

Ursodeoxycholic Acid Replacement Therapy

One effective treatment option is ursodeoxycholic acid replacement therapy. This therapy has been shown to be particularly beneficial in treating congenital bile acid synthesis defect type 3 caused by oxysterol 7α-hydroxylase deficiency [2]. Ursodeoxycholic acid helps to replace the deficient bile acids and improve liver function.

Chenodeoxycholate Therapy

Another treatment option is chenodeoxycholate therapy. This involves administering oral chenodeoxycholate at a dose of 5 mg/kg/d, which has been reported to be effective in managing symptoms and improving outcomes [3].

Cholic Acid Therapy

Cholic acid therapy creates a pool of bile acids that stimulates bile flow and facilitates fat-soluble vitamin absorption. This therapy has been shown to be an effective treatment option for children with primary bile acid synthesis defects [4]. Cholic acid replacement has also been reported to suppress atypical bile acid synthesis.

Treatment Outcomes

The outcomes of these treatments have been promising, with patients experiencing significant improvements in symptoms and liver function. In most cases, patients respond well to treatment with missing bile acid replacement therapy, particularly cholic acid [5].

In conclusion, the treatment options for congenital bile acid synthesis defects include ursodeoxycholic acid replacement therapy, chenodeoxycholate therapy, and cholic acid therapy. These therapies have been shown to be effective in managing symptoms and improving outcomes for affected individuals.

References:

[1] Congenital bile acid synthesis defect type 1 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile [7].

[2] Ursodeoxycholic acid replacement therapy is an effective and affordable treatment for congenital bile acid synthesis disorder type 3 caused by oxysterol 7α-hydroxylase deficiency [2].

[3] Immediately after diagnosis, patients were treated with oral chenodeoxycholate 5 mg/kg/d. Outcomes: The patients' symptoms, signs, and primary liver function tests improved significantly [4].

[4] Oral cholic acid (CA) replacement has been shown to be an effective therapy in children with primary bile acid synthesis defects [6].

[5] Cholic acid therapy creates a pool of bile acids which stimulates bile flow and facilitates fat soluble vitamin absorption and suppresses atypical bile acid synthesis [5].

[7] Congenital bile acid synthesis defect type 1 is a disorder characterized by cholestasis, a condition that impairs the production and release of a digestive fluid called bile [7].

The differential diagnosis for congenital bile acid synthesis defects involves considering various conditions that present with similar symptoms, such as progressive familial intrahepatic cholestasis, biliary atresia, and other liver diseases.

According to the medical literature [1], differential diagnoses include:

• Progressive familial intrahepatic cholestasis
• Biliary atresia
• Alagille syndrome
• Byler disease
• Other rare metabolic disorders

It's also worth noting that congenital bile acid synthesis defects can present with a wide range of symptoms, making diagnosis challenging [2]. A high index of suspicion is required to prevent the diagnosis being overlooked.

In terms of specific conditions, biliary atresia and intrahepatic cholestasis in children are often considered in the differential diagnosis for congenital bile acid synthesis defects [3].

References:

[1] Stieger B, et al. Differential interaction of bile acids with their membrane transporters. (Context 2)

[2] A high index of suspicion is required to prevent the diagnosis of a bile acid synthesis defect being overlooked, as the clinical presentations of these rare disorders can be similar to those of other causes of neonatal liver failure, neonatal cholestasis and chronic liver disease. (Context 2)

[3] by F LingJuan · 2010 · Cited by 1 — Differential diagnosis of biliary atresia and intrahepatic cholestasis in children[J]. Journal of Clinical Hepatology, 2015, 31(8): 1252-1256. (Context 6)