Abstract
Very-long-chain fatty acids (VLCFAs) are commonly used to diagnose peroxisomal disorders, but elevated levels may also result from other non-peroxisomal causes, leading to diagnostic challenges. We report the case of a 2-year-old girl presenting with growth retardation and diarrhea, with laboratory investigations revealing elevated VLCFA levels suggestive of a peroxisomal disorder. Despite initial suspicion, genetic panels for peroxisomal and dyslipidemia-associated genes were negative. Whole exome sequencing (WES) ultimately revealed a pathogenic variant in the ABCG8 gene, consistent with a diagnosis of sitosterolemia, a rare autosomal recessive condition characterized by elevated plant sterols. Elevated plant sterols in sitosterolemia may interfere with VLCFA analysis, potentially leading to falsely elevated results and incorrect suspicion of peroxisomal dysfunction. This case underscores the importance of including sitosterolemia in the differential diagnosis for elevated VLCFA levels, particularly in patients with atypical presentations for peroxisomal disorders. It also highlights the role of WES in establishing an accurate diagnosis when biochemical findings are ambiguous. More studies are needed to evaluate the effects of plant sterols on VLCFA measurements. This report contributes to the literature by demonstrating the utility of genetic testing in clarifying challenging diagnostic scenarios involving elevated VLCFAs.