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progressive familial intrahepatic cholestasis 1

Description

Progressive Familial Intrahepatic Cholestasis 1 (PFIC1)

PFIC1, also known as Byler disease, is a rare genetic disorder that affects the liver's ability to transport bile acids into the bile canaliculi. This condition is characterized by mutations in the ATP8B1 gene, which codes for the FIC1 protein.

Key Features:

  • Genetic Cause: PFIC1 is caused by mutations in the ATP8B1 gene, leading to a deficiency of the FIC1 protein.
  • Liver Disease: The condition causes progressive liver disease, which can lead to fibrosis and end-stage liver disease before adulthood.
  • Cholestasis: PFIC1 patients experience cholestasis, pruritus (itching), and jaundice due to impaired bile formation.
  • Autosomal Recessive: PFIC1 is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

References:

  • [5] describes PFIC1 as characterized by mutations in the ATP8B1 gene.
  • [9] notes that PFIC1 denotes individuals with defects in the Familial Intrahepatic Cholestasis 1 gene (FIC1 = ATP8B1), leading to progressive disease.
  • [3] mentions that main clinical manifestations of PFIC include cholestasis, pruritus, and jaundice.

Additional Characteristics

  • A rare genetic disorder affecting the liver's ability to transport bile acids into the bile canaliculi.
  • Caused by mutations in the ATP8B1 gene leading to a deficiency of the FIC1 protein.
  • Characterized by progressive liver disease, cholestasis, pruritus, and jaundice due to impaired bile formation.
  • Inherited in an autosomal recessive pattern requiring two copies of the mutated gene.

Signs and Symptoms

Progressive Familial Intrahepatic Cholestasis (PFIC) 1 is a rare genetic disorder that affects the liver's ability to transport bile acids into the intestine. The signs and symptoms of PFIC 1 can vary in severity and may include:

  • Severe itching (pruritus): This is often the hallmark feature of PFIC 1, presenting in infancy or early childhood [4].
  • Jaundice: Yellowing of the eyes and skin due to a buildup of bilirubin in the blood [2, 3, 6].
  • Poor weight gain and growth: Difficulty absorbing fats and fat-soluble vitamins can lead to faltering growth (failure to thrive) [7].
  • Deficiencies in fat-soluble vitamins: Vitamin K deficiency can cause bleeding problems, while vitamin D deficiency can affect bone growth [3, 5].
  • Short stature: Some individuals with PFIC 1 may experience persistent short stature [5].
  • Deafness: Sensorineural deafness has been reported as an extrahepatic manifestation of PFIC 1 [5].
  • Bleeding and pancreatitis: Vitamin K deficiency can cause bleeding problems, while pancreatitis is another rare complication [3, 9].

It's essential to note that the severity and presentation of these symptoms can vary widely among individuals with PFIC 1.

Additional Symptoms

Diagnostic Tests

Based on the provided context, here are the diagnostic tests for Progressive Familial Intrahepatic Cholestasis (PFIC) 1:

  • Genetic testing is the only reliable way to distinguish between PFIC1 and PFIC2 [3].
  • Blood tests can also be used as part of the diagnosis process.
  • Liver biopsy may be performed to confirm the diagnosis.

It's worth noting that genetic testing involves DNA sequencing of the 27 coding exons, which is a specific and detailed test [1].

Additionally, other diagnostic tests such as liver function tests, serum bile acids, and imaging studies can help rule out other causes of liver disease, but are not specifically used to diagnose PFIC [7].

Additional Diagnostic Tests

  • Blood tests
  • Genetic testing
  • Liver biopsy

Treatment

Treatment Options for Progressive Familial Intrahepatic Cholestasis (PFIC) 1

Progressive Familial Intrahepatic Cholestasis (PFIC) 1 is a rare genetic disorder that affects the liver's ability to transport bile acids. While there are various treatment options available, drug therapy plays a crucial role in managing this condition.

Initial Treatment: Ursodeoxycholic Acid (UDCA)

The initial treatment for all PFIC subtypes, including PFIC 1, is Ursodeoxycholic acid (UDCA) [4]. UDCA has been reported to be minimally effective but is often administered off-label to patients with PFIC [6]. The recommended dose of UDCA is 10-30 mg/kg per day.

Emerging Treatments: Odevixibat and Maralixibat

Two new drugs, odevixibat and maralixibat, have been developed and approved in the last few years for the treatment of PFIC [1]. These drugs help bile in the intestines leave the liver more efficiently. Odevixibat has been shown to reduce pruritus (itching) and lower serum bile acids in patients with PFIC [8].

Other Emerging Treatments

Other emerging treatments in the pipeline for PFIC include systemic IBAT inhibitors, synthetic bile acid derivatives, and compounds targeting bile acid synthesis via the FXR pathway [2]. These new treatments aim to improve liver function and reduce symptoms associated with PFIC.

Surgical Treatment

In some cases, surgical treatment may be necessary to address complications related to PFIC. However, this is typically reserved for patients who do not respond to medical therapy or have severe liver damage [7].

Key Takeaways:

  • Ursodeoxycholic acid (UDCA) is the initial treatment for all PFIC subtypes.
  • Odevixibat and maralixibat are emerging treatments that have been approved for PFIC.
  • Other emerging treatments, such as IBAT inhibitors and synthetic bile acid derivatives, are being explored.
  • Surgical treatment may be necessary in some cases.

References:

[1] WFJ Hof. Two new drugs for PFIC have been developed and approved in the last few years: odevixibat and maralixibat.

[2] WFJ Hof. Other emerging treatments in the pipeline include systemic IBAT inhibitors, synthetic bile acid derivatives, compounds targeting bile acid synthesis via the FXR pathway.

[4] M Gunaydin. Ursodeoxycholic acid (UDCA) is the initial treatment for all PFIC subtypes.

[6] P McKiernan. Ursodeoxycholic acid (UDCA) is minimally effective but is often administered off-label to patients with PFIC.

[7] Treatment options for PFIC can include drugs to treat cholestasis and surgery.

[8] RJ Thompson. Study results from PEDFIC 1 indicated that odevixibat can reduce pruritus and lower serum bile acids in patients with PFIC.

Recommended Medications

  • Maralixibat
  • Odevixibat
  • Systemic IBAT inhibitors
  • Synthetic bile acid derivatives
  • Compounds targeting bile acid synthesis via the FXR pathway
  • ursodeoxycholic acid

💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.

Differential Diagnosis

Differential Diagnoses for Progressive Familial Intrahepatic Cholestasis (PFIC) Type 1

Progressive familial intrahepatic cholestasis (PFIC) type 1 is a rare genetic disorder that affects the liver's ability to secrete bile. When considering differential diagnoses, it's essential to rule out other conditions that may present with similar symptoms.

Other Autosomal Recessive PFIC-like Diseases

Several other autosomal recessive diseases can resemble PFIC in terms of their clinical presentation and laboratory findings [2, 7]. These include:

  • Benign Recurrent Intrahepatic Cholestasis Type 1 (BRIC1): Caused by mutations in the ATP8B1 gene, BRIC1 is a less severe form of cholestasis that can be distinguished from PFIC based on its milder clinical course [8].
  • Primary Bile Acid Synthesis Defects: These defects can present with similar laboratory findings to PFIC, including elevated gamma-glutamyl transferase (GGT) levels. However, they are typically associated with normal or near-normal liver function tests [3].

Other Conditions to Consider

In addition to the above-mentioned conditions, other diseases that may be considered in the differential diagnosis of PFIC type 1 include:

  • Liver Diseases Resembling PFIC with Normal GGT: Several other liver diseases can present with similar clinical features to PFIC, even when GGT levels are normal [7].
  • Antenatal Diagnosis: In some cases, antenatal diagnosis may be considered in the differential diagnosis of PFIC type 1.

Key Takeaways

When considering differential diagnoses for PFIC type 1, it's essential to rule out other conditions that may present with similar symptoms. These include BRIC1, primary bile acid synthesis defects, and liver diseases resembling PFIC with normal GGT levels. A thorough evaluation of laboratory findings and clinical presentation is crucial in making an accurate diagnosis.

References:

[2] Progressive familial intrahepatic cholestasis (PFIC) refers to heterogeneous group of autosomal recessive liver disorders of childhood in which cholestasis of hepatocellular origin often presents in the neonatal period or first year of life and leads to death from liver failure at ages usually ranging from infancy to adolescence [1,2].

[7] Several other autosomal recessive PFIC-like diseases are known. Liver diseases resembling PFIC with normal GGT levels can also be considered in the differential diagnosis.

[8] Mutations in the ATP8B1 gene cause a less severe form of cholestasis, BRIC1, which is distinct from PFIC based on its milder clinical course.

Additional Differential Diagnoses

Additional Information

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