Sitosterolemia (sitosterolemia) - ABCG5 or ABCG8 Genes

The sitosterolaemia is a disorder in which the phytosterols from vegetable oils, nuts and other plant foods accumulate in the blood and tissues. Sitosterol is one of several plant sterols which accumulate in this disease, with a blood level of 30 to 100 times above normal. Cholesterol, may be lightly or moderately elevated in many people with sitosterolaemia. Cholesterol levels are especially high in some affected children.

Signs and symptoms of sitosterolaemia begin to appear after foods containing plant sterols are introduced into the diet. These signs can include atherosclerosis, xanthoma, joint stiffness and blood abnormalities. Sometimes, blood abnormalities are the only signs of the disease. For example, erythrocytes can undergo hemolysis prematurely, resulting in hemolytic anemia. Sometimes those affected have stomatocytes and macrothrombocytopenia.


Sitosterolemia is due to mutations in the ABCG5 (ATP binding cassette subfamily G member 5) gene, located on the short arm of chromosome 2 (2p21) or ABCG8 (ATP binding cassette subfamily G member 8) gene, located on the arm short of chromosome 2 (2p21). These genes encode two halves of a protein called sterolin (sterolin-1 and sterolin-2, respectively). This protein is involved in the elimination of the plant sterols they can not be used by human cells. The sterolin is a carrier protein found primarily in cells of the intestines and liver. This protein also helps regulate cholesterol levels by eliminating about 50% of dietary cholesterol that is absorbed by the body.

They have identified at least 24 mutations in the gene ABCG5 and 28 ABCG8 gene mutations in people with sitosterolaemia. These genetic changes result in a protein that alters defective sterolin removing plant sterols and, to a lesser extent cholesterol from the body. These fatty substances build up in the arteries, skin and other tissues, which causes atherosclerosis, xanthoma, and additional signs and symptoms of sitosterolemia. Excess plant sterols such as sitosterol, in erythrocytes probably causes their cell membranes become rigid and prone to rupture, resulting in hemolytic anemia. Changes in lipid composition of membranes of erythrocytes and platelets may explain other blood abnormalities that sometimes occur in sitosterolemia.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with sitosterolemia, by complete PCR amplification of exons ABCG5 and ABCG8 delos genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).