Biallelic ABCG8 Variants or Biochemical Evidence of Sitosterolemia: A Case Report

Sitosterolemia is a rare lipid disorder characterized by xanthomas, premature atherosclerotic cardiovascular disease (ASCVD), and abnormally elevated circulating low-density lipoprotein cholesterol (LDL-c) measurements. Pathogenic variants in adenosine triphosphate (ATP)-binding cassette transporters lead to the accumulation of phytosterols. A child presented to the pediatric cardiology clinic with an incidentally noted presumed pathogenic variant and a variant of unknown significance in a sitosterolemia gene but had normal fasting lipids and no accumulation of circulating phytosterols. This case underscores the importance of phenotype-driven management and universal lipid screening, while highlighting the challenges of a gene-first testing/screening approach.