Sitosterolemia: clinical, biochemical and molecular characteristics in a 3 years old boy with marked hypercholesterolemia
Abstract
Background: Sitosterolemia is a rare, autosomal recessive inherited disorder of lipid metabolism, associated with an abnormal transport of plant sterols in a small intestine and a liver due to malfunction of a transport protein ABCG5/ABCG8. Disorder is associated with significant hyperphytosterolemia and also with hypercholesterolemia in most pediatric patients, tuberous and tendinous xanthomas, hemolytic anemia, macrothrombocytopenia, abnormal bleeding, splenomegaly, premature atherosclerosis, arthritis, failure to thrive and hepatopathy.
A rare finding of normocholesterolemia and normal levels of phytosterols in breastfed infants might result in a delay in diagnosis. Patients with sitosterolemia respond well to a low cholesterol and a low plant sterol diet in combination with ezetimibe therapy.
Here, we report clinical, biochemical and molecular genetic data of a boy with sitosterolemia. Case report: 3 years old boy has been monitored since 7 months of age for hypercholesterolemia (16-25.6 mmol/l), found accidentally.
Family history was negative. Since one year of age a failure to thrive was documented, weight/lenght ratio dropped from 75th to 8.8th percentile.
At the age of 20 months laboratory tests showed significantly increased levels of serum sitosterol (13 times above normal level) and campesterol (4 times above normal level). Molecular genetic analysis revealed compouned heterozygosity for a previously described pathogenic mutation p.Arg446* and another, up to now unpublished, probably pathogenic variant p.Arg419Cys in the ABCG5 gene.
Both parents were confirmed as healthy mutation carriers. Conclusion: We presented the first Czech patient with sitosterolemia carrying mutations in ABCG5.
Patient is on a low-cholesterol and a low-plant sterol diet and ezetimibe therapy. During 16 months of therapy, level of total cholesterol and also of LDL cholesterol almost normalized and serum concentration of plant sterols decreased significantly.
Therefore, sitosterolemia should be considered in the differential diagnosis of severe hypercholesterolemia in children.