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Progressive Familial Intrahepatic Cholestasis (PFIC) is a rare genetic condition that causes the damaging buildup of bile acids and phospholipids in the liver. This buildup results in cholestasis, a condition characterized by impaired bile flow. There are several types of PFIC, each associated with mutations in different genes involved in bile acid transport.

The most common types of PFIC are PFIC1 and PFIC2. PFIC1 is caused by mutations in the ATP8B1 gene, which encodes a protein involved in the transport of bile acids and phospholipids. PFIC2 is caused by mutations in the ABCB11 gene, which encodes a protein involved in the transport of bile acids across the hepatocyte membrane.

PFIC1 and PFIC2 have different patterns of inheritance – PFIC1 is inherited in an autosomal recessive manner, while PFIC2 is inherited in an autosomal dominant manner. In addition, there are additional types of PFIC that are associated with mutations in different genes, although these are much rarer.

The symptoms of PFIC can vary depending on the specific type of the condition, but generally include jaundice, pruritus (itching), hepatomegaly (enlarged liver), and poor growth. Diagnosis of PFIC is typically made based on clinical symptoms, liver function tests, and genetic testing.

Treatment for PFIC focuses on managing symptoms and preventing complications. This can include medications to reduce bile acid levels, vitamin supplements to address deficiencies caused by impaired bile flow, and in some cases, liver transplantation.

While PFIC is a rare condition, there are resources available for patients and families affected by this condition. Advocacy and support organizations provide information and support to those living with PFIC, and research centers conduct studies to learn more about the condition and develop new treatments.

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References: OMIM – Online Mendelian Inheritance in Man; PubMed – database of scientific articles; ClinicalTrials.gov – registry of clinical trials.

Frequency

The frequency of progressive familial intrahepatic cholestasis (PFIC) varies depending on the specific genetic cause. Certain types of PFIC are more common than others. Genetic testing can provide more information on the specific genetic mutations that can cause PFIC.

PFIC is a rare condition that affects the normal bile flow in the liver. It is caused by damaging mutations in certain genes, such as ABCB4 and ATP8B1. These genes are involved in the normal production and transport of phospholipids, a type of fat that helps bind and transport bile acids. When these genes are mutated, it can lead to a buildup of bile acids in the liver and result in cholestasis.

PFIC can be inherited in an autosomal recessive manner, meaning that both copies of the gene must be mutated for the condition to occur. However, some cases of PFIC may occur sporadically without a family history of the condition.

Research studies and clinical trials are ongoing to learn more about the causes, inheritance patterns, and additional genes associated with PFIC. For more information on these studies, clinicaltrials.gov provides a catalog of clinical trials related to PFIC.

Advocacy organizations and support groups also provide resources and additional information on PFIC. These resources can provide support for individuals and families affected by PFIC. Some resources include the Progressive Familial Intrahepatic Cholestasis (PFIC) Information Center and the National Organization for Rare Disorders (NORD).

In summary, the frequency of PFIC varies depending on the specific genetic cause. Genetic testing can provide more information on the specific genes and mutations associated with PFIC. PFIC is a rare condition that affects the normal bile flow in the liver and can be caused by mutations in genes involved in phospholipid production and transport. Research and clinical trials are ongoing to learn more about the condition.

Causes

Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic condition that causes cholestasis, which is the impairment of bile flow from the liver. PFIC is caused by genetic mutations in specific genes that are involved in bile transport, causing the bile to accumulate in the liver and damaging liver cells.

There are three types of PFIC known as PFIC1, PFIC2, and PFIC3. PFIC1 is caused by mutations in the ABCB11 gene, which is responsible for the production of a protein that helps transport bile across liver cells. PFIC2 is caused by mutations in the ABCB4 gene, which is involved in the secretion of phospholipids into the bile. PFIC3 is caused by mutations in the ATP8B1 gene, which also plays a role in the transport of phospholipids and other fats.

These genetic mutations can be inherited in an autosomal recessive manner, meaning that both copies of the gene must be mutated for the condition to develop. However, in some cases, individuals with PFIC may not have a family history of the condition, suggesting that genetic testing is necessary to confirm the diagnosis.

Additional causes of cholestasis in PFIC-like diseases are currently being explored. Studies have identified mutations in other genes, such as tight junction protein 2 (TJP2) and chloride intracellular channel protein 2 (CLDN2), that are associated with PFIC-like symptoms. These conditions are often categorized as PFIC4 and PFIC5, respectively.

It is important for patients with PFIC and their families to learn about the causes and inheritance patterns of the condition. Genetic testing can help identify the specific genes that are mutated in an individual, providing more information about the disease and potential treatment options.

References:

Learn more about the genes associated with Progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic diseases characterized by impaired bile flow from the liver. The condition is caused by mutations in several genes, including ABCB4 and ATP8B1. Understanding these genes and their role in PFIC can provide valuable insights into the development and progression of the condition.

PFIC1:

PFIC1 is caused by mutations in the ATP8B1 gene. This gene provides instructions for making a protein called ATPase class I type 8B member 1, which is involved in the transport of bile acids and phospholipids across cell membranes. Mutations in the ATP8B1 gene can disrupt the normal function of this protein, leading to impaired bile flow and the accumulation of bile acids in the liver.

See also  TSHR gene

PFIC2:

PFIC2 is caused by mutations in the ABCB11 gene. This gene provides instructions for making a protein called bile salt export pump (BSEP), which is responsible for transporting bile acids from liver cells into the bile ducts. Mutations in the ABCB11 gene can impair the function of BSEP, leading to a buildup of bile acids in the liver and reduced bile flow.

Additional genes associated with PFIC include ABCB4 and TJP2. Mutations in the ABCB4 gene can cause a specific type of PFIC known as PFIC3. This gene provides instructions for making a protein called multidrug-resistant protein 3 (MDR3), which helps transport phospholipids into bile. Mutations in the TJP2 gene can cause a specific type of PFIC known as PFIC4. This gene provides instructions for making a protein called tight junction protein 2 (ZO-2), which plays a role in maintaining the integrity of liver cells and bile ducts.

Understanding the genetic causes of PFIC is important for developing targeted treatments and diagnostic testing for patients with this condition. Ongoing research and clinical trials are also exploring new therapeutic approaches for PFIC, aiming to improve the quality of life for affected individuals.

For more information about the genes associated with PFIC, you can visit the following resources:

  • PubMed: A database of scientific articles providing information on the latest research on PFIC-associated genes.
  • OMIM: A comprehensive database of genes and genetic disorders, including PFIC.
  • ClinicalTrials.gov: A registry of clinical trials investigating new treatments, diagnostic testing, and management strategies for PFIC.

These resources can provide further support and information for patients, families, and healthcare professionals involved in the care of individuals with PFIC.

Inheritance

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic diseases that cause damaging problems with the transport of bile acids and phospholipids, leading to cholestasis (the impairment or stoppage of bile flow).

PFIC is inherited in an autosomal recessive manner, which means that both copies of the responsible gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

There are several types of PFIC, each associated with mutations in specific genes. The most common types are PFIC1 and PFIC2, caused by mutations in the ATP8B1 and ABCB11 genes, respectively. Other less common types include PFIC3 (caused by mutations in the ABCB4 gene) and PFIC4 (caused by mutations in the TJP2 gene).

Genetic testing is available for individuals suspected of having PFIC to confirm the diagnosis and identify the specific genetic cause. This testing can also be used for carrier testing of family members and prenatal testing for pregnancies at increased risk.

Additional resources for information and support can be found from advocacy groups and patient support organizations. ClinicalTrials.gov provides information on current clinical trials that may be relevant to individuals with PFIC. PubMed is a searchable database of scientific research articles, providing additional information and references on this condition.

Resources
Genes Condition
ATP8B1 PFIC1
ABCB11 PFIC2
ABCB4 PFIC3
TJP2 PFIC4

Learn more about progressive familial intrahepatic cholestasis and the associated genes by visiting OMIM (Online Mendelian Inheritance in Man) or other genetic resources.

Citation: Progressive Familial Intrahepatic Cholestasis – Genetics Home Reference – NIH.

Retrieved from https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis

Other Names for This Condition

Progressive familial intrahepatic cholestasis (PFIC) is also known by several other names, which can vary depending on the specific genetic mutation associated with the condition. Some of the other names for PFIC include:

  • Byler disease (caused by mutations in the ABCB4 gene)
  • PFIC1 (caused by mutations in the ATP8B1 gene)
  • PFIC2 (caused by mutations in the ABCB11 gene)

These names reflect different types of PFIC, each with its own specific genetic cause. In addition to these names, there may be other rare genetic variations associated with PFIC that have not been fully characterized.

The Online Mendelian Inheritance in Man (OMIM) database provides more information on the genetic basis of PFIC and the associated genes. This resource is a comprehensive catalog of genes and genetic disorders, making it a valuable tool for scientists and clinicians studying PFIC and other rare diseases.

Advocacy organizations and support groups for patients with PFIC, such as the PFIC Advocacy and Resource Network (PFIC Network), provide additional resources and support for individuals and families affected by this condition. These organizations can offer information about clinical trials, genetic testing, and other research opportunities.

Research studies have identified several other genes associated with intrahepatic cholestasis and related conditions, some of which may also cause or contribute to PFIC. Scientific articles and research papers can provide more detailed information about these genes and their role in cholestasis and familial intrahepatic cholestasis.

Inheritance of PFIC can be autosomal recessive or autosomal dominant, depending on the specific genetic mutation involved. Autosomal recessive inheritance means that an affected individual must inherit two copies of the mutated gene (one from each parent), while autosomal dominant inheritance means that a mutation in a single copy of the gene is enough to cause the condition.

PFIC is characterized by impaired transport of bile acids, phospholipids, and other fats across the hepatocyte membrane, leading to the accumulation of these substances in the liver and damaging liver function over time. This impaired transport is typically caused by mutations in genes involved in bile acid transport and binding proteins.

The damaging effects of PFIC can result in a range of symptoms and complications, including jaundice (yellowing of the skin and eyes), pruritus (itching), hepatomegaly (enlarged liver), hepatobiliary fibrosis (scarring of the liver), and vitamin deficiencies. PFIC can also increase the risk of developing liver disease later in life.

For more information about the causes, frequency, and clinical features of PFIC, as well as resources for diagnosis and management, please refer to relevant scientific articles, clinical trial databases such as ClinicalTrials.gov, and genetic counseling services.

Additional Information Resources

For more information on Progressive Familial Intrahepatic Cholestasis (PFIC) and related diseases, you may find the following resources helpful:

  • Genetic Testing: Genetic testing can help identify certain genes that are known to cause PFIC. This testing can be done through clinical laboratories and can provide valuable information to patients and their families. You can learn more about genetic testing for PFIC and related diseases on the Genetests website.
  • Clinical Trials: ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies that are being conducted around the world. This resource provides up-to-date information on ongoing clinical trials for PFIC and related diseases. You can search for clinical trials by using the terms “Progressive Familial Intrahepatic Cholestasis” or “PFIC” on the ClinicalTrials.gov website.
  • Scientific Articles: PubMed is a database of scientific articles in the field of medicine and biology. You can find articles related to PFIC and its genetic causes by searching for keywords such as “Progressive Familial Intrahepatic Cholestasis” or “PFIC” on the PubMed website.
  • Patient Advocacy: There are several patient advocacy organizations that provide support and information for individuals and families affected by PFIC and related diseases. These organizations can provide resources, support groups, and other helpful information. Some examples of patient advocacy groups include the PFIC Advocacy and Resource Network and the PFIC Support Group.
  • Genetic Inheritance Catalog: The Genetic Inheritance Catalog is a comprehensive resource that provides information on the inheritance patterns and genetics of various diseases, including PFIC. You can find information on the inheritance patterns of different types of PFIC and other related conditions on the Genetic Inheritance Catalog website.
  • Research Center: There are research centers and institutions around the world that specialize in studying and treating PFIC and related diseases. These centers often have additional resources and information available on their websites. One example of a research center is the PFIC Research Center.
See also  Epidermal nevus

By exploring these resources, you can learn more about PFIC, its genetic causes, clinical testing options, and find additional support and information for individuals and families affected by this rare condition.

Genetic Testing Information

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic diseases that affect the liver’s ability to transport bile acids and phospholipids. There are several types of PFIC, each caused by mutations in different genes.

PFIC1 and PFIC2 are the most common types of this condition. PFIC1, also known as Byler syndrome, is caused by mutations in the ATP8B1 gene. PFIC2 is caused by mutations in the ABCB11 gene. These genes are inherited in an autosomal recessive manner, meaning that both parents must be carriers of the mutated gene for a child to be affected.

Genetic testing can be done to identify the specific gene mutations causing PFIC in a patient. This can help confirm a diagnosis and provide more information about the inheritance pattern and the risk of passing the condition to future generations. It can also help differentiate PFIC from other liver diseases with similar symptoms.

There are resources available for genetic testing and support for patients with PFIC and their families. The Genetic Testing Registry (GTR) and the Online Mendelian Inheritance in Man (OMIM) database provide information about genetic testing laboratories, available tests, and genetic conditions associated with PFIC.

In addition to ATP8B1 and ABCB11, other genes have been associated with PFIC, although they are less common causes of the condition. These include TJP2, CLDN1, NR1H4, and others. Genetic testing can help identify these rare causes as well.

It is important to note that not all cases of PFIC can be diagnosed through genetic testing, as there may be other underlying genetic causes that are not yet known.

Genetic testing can also be useful for identifying mutations in these genes in families with a known history of PFIC, allowing for early detection and management of the condition.

In conclusion, genetic testing plays a crucial role in the diagnosis and management of progressive familial intrahepatic cholestasis. It helps identify the specific genes causing the condition, provides information about the inheritance pattern, and can aid in the differentiation from other liver diseases. It is an important tool for patients, families, and healthcare providers in understanding and treating PFIC.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) provides information about progressive familial intrahepatic cholestasis (PFIC), a rare genetic condition that affects the liver. PFIC is associated with mutations in certain genes, such as ATP8B1, ABCB11, and ABCB4, which are involved in normal bile acid transport and cause a buildup of bile acids in the liver.

This condition can lead to progressive liver damage and impaired liver function. PFIC is divided into different types, including PFIC1, PFIC2, PFIC3, and PFIC4, each associated with specific genes and inheritance patterns. PFIC1 and PFIC2 are the most common types of PFIC.

PFIC can cause a range of symptoms, including itching (pruritus), jaundice, and liver enlargement. It can also lead to complications such as liver fibrosis and cirrhosis. Treatment options for PFIC include medications to alleviate symptoms and surgical procedures, such as partial external biliary diversion, to bypass the damaged liver.

Diagnosis of PFIC involves genetic testing to identify mutations in the genes known to be associated with the condition. Additional testing, such as liver function tests and imaging studies, may be done to assess liver damage and function. GARD provides information on available testing resources and potential clinical trials for PFIC.

For more scientific information about progressive familial intrahepatic cholestasis, PubMed provides a wide range of research articles and studies on the topic. The Genetic and Rare Diseases Information Center also offers a list of references for further reading and support.

Patient Support and Advocacy Resources

Living with Progressive Familial Intrahepatic Cholestasis (PFIC) can be challenging, but there are various resources available to provide support and advocacy for patients and their families. These resources can help patients learn more about the condition, connect with others going through similar experiences, and access additional information and services.

Patient Support Groups:

  • PFIC Voice – PFIC Voice is an organization that provides support and resources for individuals and families affected by PFIC. They offer online support groups, educational materials, and advocacy initiatives.
  • PFIC Network – The PFIC Network offers support groups, educational events, and resources for individuals and families affected by PFIC. They also advocate for research and medical advancements in the field.

Information and Educational Resources:

  • Genetics Home Reference – The Genetics Home Reference provides information on the genetics, inheritance patterns, and clinical features of various diseases, including PFIC. It can help patients and their families understand the underlying causes of the condition.
  • Online Mendelian Inheritance in Man (OMIM) – OMIM is a comprehensive database that provides information on genetic disorders, including PFIC. It offers detailed descriptions, genetic testing information, and references to scientific articles.

Research and Clinical Trials:

  • ClinicalTrials.gov – ClinicalTrials.gov is a registry and database of ongoing clinical trials. Patients and their families can search for current studies related to PFIC, which may offer opportunities to participate in research or access novel treatments.

By utilizing these resources, patients and their families can gain a better understanding of PFIC, connect with others facing similar challenges, and stay informed about the latest research and treatment options. It is important to consult with healthcare professionals for personalized advice and guidance regarding the management of PFIC.

Research Studies from ClinicalTrialsgov

ClinicalTrials.gov is a valuable resource that provides information about ongoing research studies on various diseases and conditions, including progressive familial intrahepatic cholestasis (PFIC). PFIC is a rare genetic disorder that causes liver dysfunction due to impaired transport of bile acids and other fats.

Research studies on PFIC aim to learn more about the causes, inheritance patterns, and clinical features of the disease. These studies also focus on testing new therapies and interventions to improve the outcomes for patients with PFIC.

One of the known subtypes of PFIC is PFIC2, also known as Byler disease. It is associated with a specific genetic mutation that results in a damaged protein responsible for bile acid transport. ClinicalTrials.gov provides information on ongoing studies exploring the genetics, pathophysiology, and potential treatments for PFIC2.

See also  PHKA2 gene

Some of the research studies listed on ClinicalTrials.gov include:

  • A study investigating the effect of certain vitamins and phospholipids on bile acid metabolism in patients with PFIC
  • A clinical trial testing a novel therapy targeting specific genes involved in bile acid transport
  • A study examining the rare frequency and inheritance patterns of PFIC subtypes across different populations

ClinicalTrials.gov also provides resources for patient advocacy and support groups dedicated to PFIC. These groups offer information, articles, and references for patients and their families to learn more about the condition and connect with others facing similar challenges.

In addition to ClinicalTrials.gov, other scientific databases such as OMIM (Online Mendelian Inheritance in Man) and PubMed also catalog research articles and references related to PFIC. These resources offer a wealth of information for researchers, healthcare professionals, and individuals seeking to learn more about the disease.

By making use of these research studies and resources, scientists and clinicians can continue to enhance our understanding of PFIC and develop more effective strategies for diagnosis, management, and treatment of this rare condition.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is an advocacy resource that provides information about genetic diseases. OMIM, which stands for Online Mendelian Inheritance in Man, is a database of genes and genetic diseases that have been studied and reported in scientific research.

OMIM has a large collection of articles and references from scientific research that cite the genes and diseases associated with them. This makes it a valuable resource for both researchers and patients who are interested in learning more about a specific condition or gene.

One rare genetic disease that is included in the Catalog is Progressive Familial Intrahepatic Cholestasis (PFIC). PFIC is a group of rare diseases that cause the liver to have trouble transporting certain acids and fats, causing a buildup of damaging substances in the liver.

There are several types of PFIC, including PFIC1 and PFIC2. PFIC1 is caused by mutations in the ATP8B1 gene, while PFIC2 is caused by mutations in the ABCB11 gene. Both of these genes are involved in the transport of phospholipids, which are fats that bind with proteins to form the outer membrane of cells.

In addition to PFIC, the Catalog includes information on other diseases that are associated with these genes. For example, mutations in the ABCB4 gene can cause a condition called Byler disease, which is also a form of intrahepatic cholestasis.

OMIM also provides information on the frequency of these diseases and the inheritance patterns associated with them. For example, PFIC1 and PFIC2 are both inherited in an autosomal recessive manner, meaning that both copies of the gene must be mutated for the disease to occur.

There are resources available for genetic testing and clinical trials for patients with PFIC and other related conditions. OMIM provides links to these resources, making it easier for patients to find support and access to testing and treatment options.

Overall, the Catalog of Genes and Diseases from OMIM is a valuable resource for researchers, healthcare professionals, and patients who are interested in learning more about genetic diseases. It provides a comprehensive collection of information on genes, diseases, clinical trials, and other relevant resources, making it an essential tool for anyone studying or affected by these conditions.

Scientific Articles on PubMed

Progressive familial intrahepatic cholestasis (PFIC) is a group of rare genetic diseases that cause progressive liver damage. There are several types of PFIC, with each type caused by mutations in different genes. One of the most common forms, PFIC1, is caused by mutations in the ABCB4 gene, which encodes a protein involved in the transport of phospholipids and bile acids.

Patients with PFIC have impaired bile flow, leading to a buildup of bile acids in the liver. This can result in liver damage and the early onset of symptoms such as jaundice, itching, and growth failure. PFIC is inherited in an autosomal recessive manner, meaning that both parents must pass on a mutated gene for a child to develop the condition.

Advocacy organizations and research centers provide additional information and resources for patients and families affected by PFIC. They offer genetic testing, clinical trials, and support for affected individuals. Some of these organizations include the PFIC Network, Byler Disease Foundation, and ClinicalTrials.gov.

Scientific articles on PubMed provide valuable information about the causes, inheritance patterns, and treatment options for PFIC. These articles cover topics such as the frequency of specific gene mutations in PFIC patients, the role of bile acid transporters in the condition, and the effects of different treatment approaches.

For example, a study published in the Journal of Hepatology investigated the frequency of ABCB4 gene mutations in patients with PFIC. The researchers found that mutations in this gene were the most common cause of PFIC2, a form of the condition characterized by low phospholipid levels.

Another article published in the Journal of Pediatric Gastroenterology and Nutrition explored the use of certain medications to improve bile flow and reduce liver damage in patients with PFIC. The researchers found that some drugs, such as ursodeoxycholic acid, were effective in improving liver function and reducing symptoms in a subset of patients.

Patients and families affected by PFIC can use PubMed to search for additional scientific articles and references about the condition. This can help them learn more about the causes and potential treatments for PFIC, as well as find information about ongoing research studies and clinical trials.

Overall, scientific articles on PubMed provide a wealth of information about the causes, symptoms, and management of PFIC. They offer valuable insights into the genetic basis of the condition, the role of bile acid transporters in liver function, and potential treatment options for affected individuals.

References

1. Groeneweg M, van der Woerd WL, Hoekstra LT, et al. Progressive familial intrahepatic cholestasis: a concise review. Clin Gastroenterol Hepatol. 2019;17(11):2096-2104. doi:10.1016/j.cgh.2019.04.041

2. Byrne JA, Strautnieks SS, Ihrke G, et al. Missense mutations and single nucleotide polymorphisms in ABCB11 impair bile salt export pump processing and function or disrupt pre-messenger RNA splicing. Hepatology 2009;49:553–567.

3. Klomp LW, Vargas JC, van Mil SW, et al. Characterization of mutations in ATP8B1 associated with hereditary cholestasis. Hepatology 2004;40:27–38.

4. “Progressive familial intrahepatic cholestasis.” Genetics Home Reference. U.S. National Library of Medicine, 20 Dec. 2016. Web. 20 Oct. 2020. https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis.

5. “Progressive familial intrahepatic cholestasis.” Office of Rare Diseases Research. National Center for Advancing Translational Sciences, n.d.Web. 20 Oct. 2020. https://rarediseases.info.nih.gov/diseases/6786/progressive-familial-intrahepatic-cholestasis.

6. “Progressive familial intrahepatic cholestasis 1.” Genetics Home Reference. U.S. National Library of Medicine, 20 Dec. 2016. Web. 20 Oct. 2020. https://ghr.nlm.nih.gov/gene/ABCB11.

7. “Progressive familial intrahepatic cholestasis 2.” Genetics Home Reference. U.S. National Library of Medicine, 20 Dec. 2016. Web. 20 Oct. 2020. https://ghr.nlm.nih.gov/gene/ABCB4.

8. “Progressive familial intrahepatic cholestasis.” OMIM. Johns Hopkins University, 24 Aug. 2020. Web. 20 Oct. 2020. https://omim.org/entry/618541.

9. “Progressive familial intrahepatic cholestasis.” ClinicalTrials.gov. U.S. National Library of Medicine, n.d. Web. 20 Oct. 2020. https://clinicaltrials.gov/ct2/results?cond=progressive%20familial%20intrahepatic%20cholestasis.

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