Cholestasis is a rare condition that involves a reduction or obstruction of bile flow fromhe liver to the small intestine. When bile flow is hindered, a waste product pigment called bilirubin can escape into the bloodstream and build up to harmful levels. This may lead tohe easily recognizable cholestatic symptoms of jaundice, itching, and impaired growth andventually to more serious health problems. Four rare genetic liver disorders- ALGS, a-1AT, bile acid synthesis and metabolism defects, and PFIC-account for about 20% to 30% of allholestasis. These four disorders compose a group of related diseases thatuse significant growth problems during childhood, serious liver problems, the need forver transplantation, and potentially death. More research on these rare liver diseases isy to develop a scientific basis for improvement in diagnostic techniques and. Current diagnostic procedures are complex, and the development of simpler diagnostic tests would facilitate early diagnosis and treatment. This study will investigatehe natural history and progression of the four previously mentioned cholestatic liver diseases to provide a better understanding of the causes and effects of the diseases.

Participation in this study will last 20 years and will consist of a baseline visit and 20ual follow-up visits. The study will enroll infants through adults 25 years of age who have, or are suspected of having, one of the four genetic cholestatic liver diseases.dividuals who are siblings of a-A1T participants and have underlying disease with novidence of liver involvement may also be enrolled. Study visits will involve review ofy history, and any clinically indicated treatments and theirutcomes; a physical exam; laboratory tests; and radiologic and imaging evaluations. Inddition to these standard of care evaluations, participants will undergo several specialh evaluations, including quality of life questionnaires, neurodevelopmentalvaluations, hearing exams, liver histology studies, and collection of serum, plasma, urine,d blood for DNA. Serum, plasma, and blood for DNA will also be collected from both biological parents and from affected siblings of participants with a-A1T or ALGS. Geneticg will be performed using the collected specimens.