From Xanthomas to Genetic Diagnosis: A Case Report of Sitosterolemia in an Infant with a Homozygous ABCG5 c.1166G>A (p.Arg389His) Variant.

INTRODUCTION

Sitosterolemia is a rare autosomal recessive disorder characterized by disrupted lipid metabolism and elevated plasma plant sterol levels. Clinical manifestations often include cutaneous and tendon xanthomas and hypercholesterolemia; delayed diagnosis can lead to cardiovascular disease and hematological abnormalities. This case report describes an 11-month-old female infant with sitosterolemia who presented with xanthomas appearing around 6 months of age. Genetic sequencing identified a homozygous ABCG5 c.1166G>A (p.Arg389His) mutation. This report aims to discuss the clinical features and genetic diagnosis of sitosterolemia caused by ABCG5 mutations, highlighting the challenges and key characteristics for early diagnosis to improve clinical awareness.

CASE AND

METHODS

Clinical data of a pediatric patient with sitosterolemia caused by a homozygous ABCG5 gene mutation were retrospectively analyzed.

RESULTS

An 11-month-old female infant developed linear xanthomas in the skin folds of her ankles at approximately 6 months of age, which progressively worsened. Blood tests revealed significantly elevated total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Sequencing of coding regions for genes associated with familial hypercholesterolemia and sitosterolemia identified a homozygous ABCG5 mutation: c.1166G>A (p.Arg389His). Sanger sequencing confirmed that this variant was inherited from each parent in a heterozygous state. The diagnosis of sitosterolemia was confirmed based on genetic testing (ABCG5/ABCG8), lipid profile results, and clinical presentation.

CONCLUSION

Sitosterolemia should be suspected in patients presenting with cutaneous xanthomas, prompting thorough investigation including lipid profiling, genetic testing, and plasma plant sterol quantification to avoid misdiagnosis as familial hypercholesterolemia (FH).