progressive familial intrahepatic cholestasis 3

Progressive Familial Intrahepatic Cholestasis (PFIC) Type 3: A Rare Liver Disorder

PFIC type 3, also known as PFIC-3, is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene. This genetic defect leads to a disruption in bile formation, resulting in progressive liver disease and ultimately liver failure.

Key Characteristics of PFIC-3:

• Genetic Cause: Mutations in the ABCB4 gene (also designated MDR3) located on chromosome 7.
• Liver Disease Progression: Progressive liver disease leading to liver failure.
• Age of Onset: Typically presents with symptoms in late infancy to adolescence.
• Symptoms:
  • Recurrent pruritus (itching)
  • Cholestatic jaundice
  • Kaolin-like stools

Understanding PFIC-3:

PFIC type 3 is a rare and serious liver disorder that requires prompt medical attention. The genetic defect responsible for this condition affects the body's ability to form bile, leading to a buildup of toxins in the liver.

References:

• [5] Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive cholestatic liver disorder caused by mutations in the ABCB4 gene.
• [9] PFIC3 usually presents with recurrent pruritus, cholestatic jaundice, and kaolin-like stools in late infancy to adolescence; while in older children and adults, it may present with more severe symptoms.

Note: The information provided is based on the search results and context provided.

Signs and Symptoms of PFIC3

PFIC3, also known as Progressive Familial Intrahepatic Cholestasis 3, is a rare liver disorder that affects the liver's ability to transport bile salts. The signs and symptoms of PFIC3 typically appear later in infancy or early childhood, although some people may be diagnosed in early adulthood.

Common Signs and Symptoms:

• Severe itching (pruritus): This is often the hallmark feature of PFIC3, causing significant discomfort and distress.
• Jaundice: Yellowing of the whites of the eyes and skin due to a buildup of bile salts.
• Difficulty gaining weight: Poor weight gain and growth are common due to a lack of bile needed to digest and absorb fat.
• Deficiencies in fat-soluble vitamins: PFIC3 can lead to deficiencies in vitamins A, D, E, and K.

Other Possible Symptoms:

• Poor appetite
• Fatigue
• Pale or clay-colored stools
• Dark urine

It's essential to note that the symptoms of PFIC3 can vary from person to person, and not everyone will experience all of these signs. If you suspect that you or a loved one may have PFIC3, it's crucial to consult with a healthcare professional for proper diagnosis and treatment.

References:

• [1] Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood. Liver failure can ...
• [2] Dec 1, 2009 — Signs and symptoms of PFIC3 usually do not appear until later in infancy or early childhood; rarely, people are diagnosed in early adulthood.
• [3] PFIC3 is a rare condition that affects the liver. People with this condition generally develop signs and symptoms during late infancy or early childhood.
• [4] Most people with PFIC3 have signs and symptoms related to liver disease only. Signs and symptoms of PFIC3 usually do not appear until later in infancy or ...
• [6] What are the signs and symptoms of PFIC? · Severe itching · Jaundice (yellowness of eyes and skin) · Difficulty gaining weight · Deficiencies in fat-soluble ...
• [7] Signs and Symptoms · Severe itching (pruritus) · Poor weight gain (due to a lack of bile needed to digest and absorb fat) and poor growth · Jaundice (yellowing of ...

Diagnostic Tests for Progressive Familial Intrahepatic Cholestasis (PFIC) Type 3

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare genetic disorder that affects the liver's ability to secrete bile. Diagnosing PFIC3 can be challenging, but several diagnostic tests can help confirm the condition.

Blood Tests

• Liver Function Tests: These blood tests can assess the general condition of the liver and provide some information about the type of PFIC.
• Gamma GT (GGT) levels: GGT is a type of liver enzyme that may help distinguish between different types of PFIC. In PFIC3, GGT levels are usually low or normal [11].

Genetic Testing

• Exome Sequencing with CNV Detection: This test can detect pathogenic variants in the ABCB4 gene, which is associated with PFIC3 [7].
• Genetic Testing Registry: Genetic testing has become the gold standard for diagnosing PFIC, including PFIC3 [3].

Liver Biopsy

• Liver biopsy: A liver biopsy can reveal expanded portal areas with proliferation of interlobular bile ducts plugged with bile, which is characteristic of PFIC3 [6].

Other Tests

• Liver ultrasonography and cholangiography: These imaging tests can help exclude other causes of childhood cholestasis and provide additional information for diagnosis.
• Metabolic screening: This test can rule out other metabolic disorders that may present with similar symptoms.

It's essential to note that establishing care with an engaged primary care provider (PCP) can improve care and shorten the time it takes to reach an accurate diagnosis [13].

References:

[3] Genetic testing has become the gold standard for diagnosing PFIC, including PFIC3. [6] Liver biopsy reveals expanded portal areas with proliferation of interlobular bile ducts plugged with bile, which is characteristic of PFIC3. [7] The authors suggest that detecting pathogenic variants in the ABCB4 gene can confirm the diagnosis of PFIC3. [11] GGT levels are usually low or normal in PFIC3. [13] Establishing care with an engaged primary care provider (PCP) can improve care and shorten the time it takes to reach an accurate diagnosis.

Treatment Options for Progressive Familial Intrahepatic Cholestasis (PFIC)

Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic disorder that affects the liver's ability to transport bile. While there is no cure for PFIC, various treatment options can help manage symptoms and improve quality of life.

Medications

Several medications have been developed to treat PFIC:

• Ursodeoxycholic acid (UDCA): This medication helps prevent liver damage by promoting the flow of bile into the intestines. It is recommended for all patients with PFIC, as it can help alleviate symptoms and slow disease progression [5].
• Odevixibat: Also known as Bylvay, this medication has been approved for treating pruritus (itching) in patients aged 3 months and older with PFIC. However, its effectiveness may vary depending on individual cases [7].
• Maralixibat: This non-surgical, pharmacological option can help interrupt the enterohepatic circulation of bile acids, improving liver function and reducing symptoms [6].

Other Therapies

In addition to medications, other therapies may be considered:

• Antipruritic therapy: Medications like UDCA can also help alleviate itching associated with PFIC.
• Fat-soluble vitamins: Patients with PFIC may require supplements of fat-soluble vitamins (A, D, E, and K) to prevent deficiencies [4].

New Developments

Recent years have seen the development

Differential Diagnoses for PFIC3

Progressive Familial Intrahepatic Cholestasis 3 (PFIC3) is a rare genetic disorder that affects the liver's ability to transport bile acids. The differential diagnosis for PFIC3 includes other conditions that present with similar symptoms and laboratory findings.

Conditions to Consider:

• Alagille Syndrome: A genetic disorder characterized by liver disease, heart problems, and other systemic features [2].
• Alpha1-Antitrypsin (AAT) Deficiency: A genetic disorder that can cause liver disease, particularly in children [2].
• Arthrogryposis-Renal Dysfunction Cholestasis (ARC): A rare genetic disorder characterized by muscle weakness, kidney problems, and liver disease [2].
• Biliary Tract Diseases: Conditions such as biliary atresia or choledochal cysts that can cause cholestatic jaundice [1].
• Cirrhosis with Elevated γ-GT: A condition where the liver becomes scarred, leading to elevated gamma-glutamyl transferase (γ-GT) levels [8].

Key Features of PFIC3:

• Cholestasis, pruritus, and jaundice are common clinical manifestations [6].
• Fibrosis and end-stage liver disease often develop in affected individuals [6].
• Laboratory findings may include elevated transaminases and alpha-fetoprotein serum levels [7].

References:

[1] Context 1 [2] Context 2 [3] Context 3 [4] Context 4 [5] Context 5 [6] Context 6 [7] Context 7 [8] Context 8