The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial for HoFH.

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. The most frequent cause is mutation in the LDL receptor gene (LDLR). LDL-C levels remain frequently above acceptable levels despite treatment with multiple existing lipid lowering drugs and/or LDL apheresis. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy may be a viable approach to treat this disease and improve response to current lipid-lowering treatments. The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial. No study drug will be administered in this screening study.

Inclusion Criteria:

• Males and females ≥ 18 years of age
• Clinical presentation consistent with homozygous FH
• Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form

Exclusion Criteria:

• Known to carry confirmed mutations in genes affecting LDL receptor functionality other than the LDLR gene
• History of cirrhosis based on documented histological evaluation or non-invasive imaging
• Documented diagnosis of any of the following liver diseases: Hepatitis B or C; Biopsy-proven nonalcoholic steatohepatitis; Biopsy-proven alcoholic liver disease; Autoimmune hepatitis; Primary biliary cirrhosis; Primary sclerosing cholangitis; Wilson's disease; Hemochromatosis; alpha1 anti-trypsin deficiency
• History of immunodeficiency diseases, including a positive HIV test result
• Previous organ transplantation
• Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study
• Inability to participate

Patients with clinical diagnosis compatible with homozygous familial hypercholesterolemia (HoFH)

The following entities may use or share information: (1) the investigator for the study and the study team, (2) the University of Pennsylvania Institutional Review Boards (the committees who oversee research on human subjects) and University of Pennsylvania Office of Regulatory Affairs, (3) The University of Pennsylvania Office of Clinical Research (the office which monitors research studies), and (4) authorized members of the University of Pennsylvania and the University of Pennsylvania Health System and School of Medicine workforce who may need to access your information in the performance of their duties (for example: to provide treatment, to ensure integrity of the research, accounting or billing matters, etc).

Has been open until 2015. Data is open until decided.

Data will be de-identified prior to sharing with other entities.