Sitosterolemia due to compound heterozygous mutations in ABCG5: a case report

BACKGROUND: Sitosterolemia is an autosomal recessive genetic disorder characterized by hypercholesterolemia and tendon/hip xanthomas, primarily caused by pathogenic mutations in the ABCG5 or ABCG8 gene. CASE PRESENTATION: We report the clinical features and therapeutic outcomes of a 29-year-old Chinese male patient diagnosed with sitosterolemia. The patient first presented with xanthomas in childhood and subsequently developed recurrent hypercholesterolemia in adulthood. Genetic sequencing identified two distinct compound heterozygous mutations in the ABCG5 gene: c.1256G>A (p.Arg419His) and c.751C>T (p.Gln251*). Lipoprotein profiling, including targeted analysis of plant sterols (xenosterols), was performed using gas chromatography-mass spectrometry. Following poor response to statin therapy, the patient was initiated on a low-plant-sterol and low-cholesterol diet, combined with ezetimibe (an NPC1L1 inhibitor). Serum total cholesterol and low-density lipoprotein cholesterol levels normalized within 2 months of this intervention. CONCLUSION: This case expands the mutational spectrum of sitosterolemia and provides valuable insights for the diagnosis and clinical management of this rare disorder.