GlycoCholic Acid Treatment for Patients With Inborn Errors in Bile Acid Synthesis

Conjugated Cholic Acid for the Treatment of Inborn Errors in Bile Acid Synthesis Involving Side-Chain Conjugation

The purpose of this research study is to determine the way (mechanisms) by which your defect in bile acid handling (metabolism) causes your liver disease or abnormality in absorption of vitamins and the effect of an investigational bile acid therapy (glycocholic acid) on your vitamin absorption and your liver disease. An investigational therapy is one that not approved by the United States Food and Drug Administration (FDA) and is being provided to you under an Investigational New Drug application from the FDA.

Inborn errors of bile acid metabolism have been established as a well recognized cause of neonatal cholestasis and fat-soluble vitamin malabsorption. Although there is extensive experience with metabolic defects in the biosynthetic pathway, few patients have identified with defects in conjugation with taurine or glycine that allows bile acids to become effective detergents. This protocol is designed to study the effect of defects of conjugation of bile acids on growth and fat-soluble vitamin malabsorption. Study subjects will have liver function studies performed, serum and urinary bile acid measurements, vitamin levels, growth measurements, bile acid pool size measurements made by stable isotope dilution mass-spectrometry, and measurements of absorption of two fat-soluble vitamins, tocopherol and vitamin D. Subjects will be treated orally with conjugates of cholic acid with follow-up laboratories performed as an outpatient and then subjects will have all of the initial studies repeated during an inpatient stay 3-12 months after starting treatment. Subjects with previous liver biopsies indicating the presence of significant liver disease will have a repeat liver biopsy after 3-12 months treatment to assess the histologic response to treatment.

Inclusion Criteria:

1. Confirmation of a diagnosis of an inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.
2. Any age
3. Participant must be willing and able to comply with study assessments and procedures.
4. The participant and/or parent/legal guardian must have signed the written informed consent document prior to study start.

Exclusion Criteria

1. No confirmed diagnosis of inborn error of bile acid synthesis/conjugation based upon urine analysis by FAB-MS.