Background: Sitosterolemia is a rare autosomal recessive disorder characterized by intestinal hyperabsorption and decreased biliary excretion of dietary plant sterol, due to mutations in adenosine-triphosphate (ATP)-binding-cassette (ABC) transporter family (ABCG8 and ABCG5).
Case report: A 7.86 years old boy was referred to the Childhood Lipid Clinic due to incidental finding of hypercholesterolemia: total cholesterol 524 mg/dl (13.54 mmol/l), LDL-cholesterol 412 mg/dl (10.65 mmol/l), HDL-cholesterol 52 mg/dl, triglycerides 55 mg/dl, ApolipoproteinA 104 mg/dl and ApoB100 253 mg/dl. Parents were unrelated. Family history was positive for obesity and hypertension. Only his father presented a mild hypercholesterolemia (total cholesterol 242 mg/dl). Anthropometric parameters were: height-SDS −2.02 and BMI-SDS −1.40. He was prepubertal and no xanthoma and/or xanthelasma, arcus corneae or splenomegaly were detected. Apolipoprotein E genotyping was E3/E3. Thyroid, liver and renal function results and echocardiography were normal. He was started on diet according to Therapeutic Lifestyle Changes (from National Cholesterol Education Program ATP III). First genetic analysis did not detected mutations on ARH and LDL-R genes. Meanwhile, his lipid profile showed an impressive improvement within 6 months of cholesterol-lowering diet: total cholesterol decreased to 203 mg/dl (5.25 mmol/l) (−39%) and LDL-cholesterol to 141 mg/dl (3.64 mmol/l) (−34%). Because of the degree and speed of his response to diet, sitosterolemia was suspected. Genetic analysis confirmed the presence of two non-sense mutation of ABCG8 gene (exon 3: c.320C>G, p.Ser107* and exon 7: c.1083 G>A, p.Trp361*) configuring our patient as a compound heterozygous.
Conclusion: Sitosterolemia shares clinical and biochemical features with homozygous familial hypercholesterolemia. Nevertheless, it is impressively responsive to cholesterol-lowering diet. In our report, we demonstrate a rapid reduction of severe hypercholesterolemia in response to dietary restriction in a young patient leading to the diagnosis of this rare disease. Early identification and treatment may prevent premature atherosclerosis.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology