Inclusion Criteria
(General)
Children and young adults diagnosed with one of the four cholestatic diseases from birth through age 25
Siblings of participants with A1AT or AGS, who themselves have alpha-1-antitrypsin deficiency or AGS but no evidence of liver disease
Both genders, all races and ethnic groups
Participant meets the enrollment criteria for one of the four cholestatic liver diseases outlined below.
(For Alpha 1)
Participants must have documented alpha 1 antitrypsin deficiency with abnormal genotype l pi type ZZ or SZ and liver disease.
Siblings of affected participants; from age birth to 25 years, who are found to be PIZZ or PISZ will be offered enrollment into the study.
(For Alagille syndrome)
The enrollment criteria for AGS and
Have evidence of liver disease (clinical, biochemical, or histological).
The enrollment criteria for AGS include five clinical scenarios in which there is a combination of a family history of AGS, the presence of paucity of interlobular bile ducts on liver biopsy, the identification of a JAGGED-1 or NOTCH2 mutation, and the following clinical criteria (symptoms or signs): cardiac, ocular, vertebral, characteristic facial features of AGS, evidence of cholestasis, intractable pruritus explainable only by liver disease, renal abnormalities.
Siblings or Parents of affected participants:
Siblings or parents (if 25 years of age or less) of AGS participants will also be offered enrollment into the study if they meet the enrollment criteria for AGS.
(PFIC (OR BRIC))
Documentation of two mutant alleles in ATP8B1, ABCB11 or ABCB4, or other genes that may be described in the future that will be shown to be confirmed causes of PFIC (OR BRIC) based on biochemical, chemical evidence and family history and evidence of cholestasis.
Exclusion Criteria
Confirmed diagnosis of other chronic cholestatic liver disease,
Short bowel syndrome/TPN related liver disease.
Chronic known infectious hepatitis (e.g. Hepatitis C, Hepatitis B, etc.)
Chronic known or strongly suspected drug toxicity (e.g. Augmentin-related cholestasis)
Acquired immunodeficiency syndrome
Acute liver failure
Extrahepatic portal vein obstruction, congenital hepatic fibrosis or congenital portosystemic shunt.
(Bile Duct) Exclusion
Peroxisomal enzyme or structural defect producing a recognized syndromic disorder, such as Zellweger syndrome, Refsum