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    Low Gamma-GT Familial Intrahepatic Cholestasis

    Important
    It is possible that the main title of the report Low Gamma-GT Familial Intrahepatic Cholestasis is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

    Synonyms

    • benign recurrent intrahepatic cholestasis types 1 and 2
    • BRIC1
    • BRIC2
    • progressive familial intrahepatic cholestasis types 1 and 2
    • PFIC1
    • PFIC2

    Disorder Subdivisions

    • BRIC type 1; mild FIC1 deficiency; mild ATP8B1 disease
    • BRIC type 2; mild BSEP deficiency; mild ABCB11 disease
    • Byler disease
    • Byler syndrome
    • Greenland childhood cholestasis
    • PFIC type 2; severe BSEP deficiency; severe ABCB11 disease
    • PFIC type 1; severe FIC1 deficiency; severe ATP8B1 disease

    General Discussion

    Low gamma-GT (GGT) familial intrahepatic cholestasis refers to a spectrum of disease, ranging from mild to severe cases. This spectrum of disease predominantly affects the liver. A variety of disorders leads to low GGT familial intrahepatic cholestasis. Children with defects in bile acid synthesis or conjugation, children with abnormalities of contact between liver cells, children with abnormalities of cell organization manifest as arthrogryposis-renal dysfunction-cholestasis syndrome, and children with "neonatal hemochromatosis" all may have low GGT familial intrahepatic cholestasis. These disorders are not covered in this report.

    This report covers the two severe and two mild forms of low GGT familial intrahepatic cholestasis that have been generally recognized, although researchers have begun to identify cases that fall in between these two extremes. The severe forms are known as progressive familial intrahepatic cholestasis (PFIC) 1 and 2 and the two milder forms are known as benign recurrent intrahepatic cholestasis (BRIC) 1 and 2. PFIC and BRIC thus lie at different ends of a spectrum. Some persons with low GGT familial intrahepatic cholestasis cannot be shown to have any of the disorders mentioned in this paragraph or in the preceding paragraph. The search continues for causes for these persons' illness or illnesses.

    The main symptom of this spectrum of disease is interruption or suppression of the flow of bile from the liver (cholestasis). Cholestasis in these disorders occurs due to defects within the liver (intrahepatic) rather than within the bile ducts outside the liver (extrahepatic). Features of cholestasis may include yellowing of the skin, mucous membranes and whites of the eyes (jaundice), failure to thrive, growth deficiency, easy bleeding, rickets, and persistent, severe itchiness (pruritus). In many cases, symptoms or signs are present at birth or during the newborn period. The more severe forms of these disorders eventually progress to cause life-threatening complications such as scarring of the liver (cirrhosis) and liver failure.

    PFIC1 and BRIC1 are caused by mutations in a gene named ATP8B1. ATP8B1 encodes a protein named familial intrahepatic cholestasis 1 (FIC1). PFIC2 and BRIC2 are caused by mutations in a gene named ABCB11. ABCB11 encodes a protein named bile salt export pump (BSEP). All forms of PFIC are inherited as an autosomal recessive trait. Some affected individuals do not have mutations in either of these genes, suggesting that additional, as of yet unidentified, forms of these disorders may exist.

    These disorders have normal or low serum levels of an enzyme known as gamma-glutamyltransferase (GGT) and, therefore, may be collectively known as low GGT familial intrahepatic cholestasis. Most children with severe cholestasis have elevated levels of this enzyme, enabling physicians to distinguish these disorders from other causes of cholestasis.

    Researchers have also identified a disorder known as PFIC type 3 or multidrug resistance protein 3 (MDR3) deficiency. Although this disorder is often grouped with PFIC1 and PFIC2, it is associated with high levels of GGT enzyme activity and the underlying defects causing this disorder are different. MDR3 deficiency is not covered in this report.

    The classification of these disorders is complicated and has continually changed as more about these disorders has become known. The classification and grouping of these disorders may undergo further changes in the future. Both these disorders were called "Byler disease" at one time, until their different genetic basis became clear. Various other names have been used for these disorders such as FIC1 deficiency for PFIC1 and BSEP deficiency for PFIC2, adding to the confusion.

    Resources

    March of Dimes Birth Defects Foundation
    1275 Mamaroneck Avenue
    White Plains, NY 10605
    Tel: (914)997-4488
    Fax: (914)997-4763
    Tel: (888)663-4637
    Email: Askus@marchofdimes.com
    Internet: http://www.marchofdimes.com

    American Liver Foundation
    39 Broadway, Suite 2700
    New York, NY 10006
    USA
    Fax: (212)483-8179
    Tel: (800)465-4837
    Email: http://www.liverfoundation.org/contact/
    Internet: http://www.liverfoundation.org

    NIH/National Institute of Diabetes, Digestive & Kidney Diseases
    Office of Communications & Public Liaison
    Bldg 31, Rm 9A06
    31 Center Drive, MSC 2560
    Bethesda, MD 20892-2560
    Tel: (301)496-3583
    Email: NDDIC@info.niddk.nih.gov
    Internet: http://www2.niddk.nih.gov/

    Children's Liver Disease Foundation
    36 Great Charles Street
    Birmingham, B3 3JY
    United Kingdom
    Tel: 01212123839
    Fax: 01212124300
    Email: info@childliverdisease.org
    Internet: http://www.childliverdisease.org

    Children's Liver Association for Support Services (C.L.A.S.S.)
    25379 Wayne Mills Place, Suite 143
    Valencia, CA 91355
    USA
    Tel: (661)263-9099
    Fax: (661)263-9099
    Tel: (877)679-8256
    Email: info@classkids.org
    Internet: http://www.classkids.org

    Canadian Liver Foundation
    3100 Steeles Avenue East Suite 801
    Markham Ontario, L3R 8T3
    Canada
    Tel: 4164913353
    Fax: 9057521540
    Tel: 8005635483
    Email: clf@liver.ca
    Internet: http://www.liver.ca

    Progressive Familial Intrahepatic Cholestasis Web Group
    2117 Tamworth Ct.
    Bedford, TX 76021
    Tel: (817)280-0784
    Email: PFICII@PFIC.org
    Internet: http://www.pfic.org/

    Childhood Liver Disease Research and Education Network
    c/o Joan M. Hines, Research Administrator
    Children's Hospital Colorado
    13123 E 16th Ave. B290
    Aurora, CO 80045
    Tel: (720)777-2598
    Fax: (720)777-7351
    Email: joan.hines@childrenscolorado.org
    Internet: http://www.childrennetwork.org

    For a Complete Report:

    This is an abstract of a report from the National Organization for Rare Disorders (NORD). A copy of the complete report can be downloaded free from the NORD website for registered users. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational therapies (if available), and references from medical literature. For a full-text version of this topic, go to www.rarediseases.org and click on Rare Disease Database under "Rare Disease Information".

    The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only. NORD recommends that affected individuals seek the advice or counsel of their own personal physicians.

    It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report

    This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.

    For additional information and assistance about rare disorders, please contact the National Organization for Rare Disorders at P.O. Box 1968, Danbury, CT 06813-1968; phone (203) 744-0100; web site www.rarediseases.org or email orphan@rarediseases.org

    Last Updated: 11/20/2010
    Copyright 2011 National Organization for Rare Disorders, Inc.

    WebMD Medical Reference from the National Organization for Rare Disorders

    Last Updated: May 28, 2015
    This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.

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