Unique Case of Familial Hypobetalipoproteinemia (FHBL)

Background/Synopsis

RG is a 43-year-old male with fatty liver disease, found to have low total and low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) levels.

Objective/Purpose

To review a clinical scenario where making the proper lipid/lipoprotein diagnosis explains the background common coincident condition (fatty liver).

Methods

Patient was seen in the office at Lipid Clinic at Penn for further evaluation.

Results

RG is a 43-year-old obese male is referred to lipid clinic for further evaluation after initial presentation of abnormal liver function tests and very low cholesterol. There is a longstanding >15 years history of abnormal liver function tests and radiographic suspicion of fatty liver disease and liver biopsy showing moderate macrovesicular steatosis with mild steatohepatitis.

Genetic testing confirmed a pathogenic variant in the APOB gene associated with a diagnosis of autosomal dominant familial hypobetalipoproteinemia (FHBL). FHBL is primarily caused by pathogenic changes in the APOB gene but it has also been associated with pathogenic variants in other genes, including ANGPTL3 and PCSK9.

This condition is associated with a low risk of developing atherosclerotic cardiovascular disease (ASCVD) and high risk for development of fatty liver disease.

RG has coronary artery calcium score (CACS) = 0. He was counseled on natural history and inheritance pattern of this condition. There is no pharmacologic treatment required, but he was advised to supplement with fat-soluble vitamins and follow up with his primary team for ongoing care of liver disease.

Conclusions

Familial hypobetalipoproteinemia (FHBL) is a monogenic lipid disorder, characterized by low total and LDL-C. This condition is due to mutations in APOB gene that disrupts normal apoB protein synthesis. This condition is typically well-tolerated, but can be a cause of fatty liver disease and even cryptogenic cirrhosis. It is important to identify the correct cause of fatty liver disease since it may be reversible and because patients regularly report feeling accused by health professional when questioned about alcohol consumption or other lifestyle transgressions as a cause of their disease. Clarification of the diagnosis will enable proper lifestyle counseling and care.