Cholestasis, progressive familial intrahepatic 1

Cholestasis, Progressive Familial Intrahepatic 1

Cholestasis, Progressive Familial Intrahepatic 1 (PFIC1) is a rare genetic disorder characterized by impaired bile flow (cholestasis) due to defects in bile formation. This condition is part of a group of disorders known as Progressive Familial Intrahepatic Cholestasis (PFIC), which are inherited in an autosomal recessive pattern and lead to liver disease in children.

Pathophysiology

PFIC1 is caused by mutations in the ATP8B1 gene, which encodes a protein involved in the transport of phospholipids across the cell membrane. This protein is crucial for maintaining the proper composition of bile, and its dysfunction leads to the accumulation of toxic substances in the liver, causing liver damage and cholestasis.

Clinical Presentation

Patients with PFIC1 typically present in infancy or early childhood with symptoms such as:

• Severe pruritus (itching)
• Jaundice
• Failure to thrive
• Hepatomegaly (enlarged liver)

As the disease progresses, it can lead to complications such as cirrhosis and liver failure.

Diagnosis

The diagnosis of PFIC1 is based on clinical presentation, laboratory findings, and genetic testing. Key diagnostic features include:

• Elevated serum bile acids
• Normal or low levels of gamma-glutamyl transferase (GGT)
• Genetic testing confirming mutations in the ATP8B1 gene

Management

Management of PFIC1 involves symptomatic treatment and may include:

• Medications to relieve itching, such as ursodeoxycholic acid and rifampicin
• Nutritional support
• Surgical interventions, such as partial external biliary diversion or ileal exclusion, to reduce bile acid levels
• Liver transplantation in cases of liver failure

Prognosis

The prognosis for individuals with PFIC1 varies. Early diagnosis and management can improve quality of life and delay the progression of liver disease. However, many patients may eventually require liver transplantation.

Genetic Counseling

Since PFIC1 is inherited in an autosomal recessive manner, genetic counseling is recommended for affected families. Parents of an affected child have a 25% chance of having another affected child with each pregnancy.

Also see

• Progressive Familial Intrahepatic Cholestasis
• Cholestasis
• Liver transplantation
• Genetic counseling