History

The history of patients with sitosterolemia may include lumps or bumps on the skin, chest pain, or myocardial infarction related to early coronary vascular disease.

Angina may be present.

Hemolytic episodes may occur.

History of arthralgias or arthritis, especially of the knees and ankles, may be present.

Individuals with sitosterolemia, especially young children, may present with extremely high LDL and total cholesterol levels. This is one cause of pseudohomozygous familial hypercholesterolemia.^[28]

Physical

Xanthomas may appear at any age, even in childhood. These may be present as subcutaneous xanthomas on the buttocks in children or in usual locations (eg, Achilles tendon, extensor tendons of the hand) in children and adults.

Xanthelasma and corneal arcus are less common.

Signs of premature coronary vascular disease, such as congestive heart failure, may be present if a patient has had previous myocardial infarction.

Decreased range of motion with possible redness, swelling, and warmth of joints due to arthritis may be present.

Splenomegaly may be present.

Causes

Genetic evaluation of familial recurrences identified sitosterolemia as an autosomal recessive disorder. A disease locus was mapped to band 2p21 in 1998. The causative mutated genes for sitosterolemia, ABCG8 and ABCG5, were identified 2 years later. Interestingly, these 2 genes both map to band 2p21 directly adjacent to each other in opposite orientation and seem to be under common regulatory control.

No other locus is suspected given the different racial origins of the families and the fact that no evidence of genetic heterogeneity has been found.

Complications

Complications may include myocardial infarction, sudden cardiac death, painful hemolysis, and arthritis.

Differential Diagnoses

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