Laboratory Studies

The following studies are indicated in suspected or diagnosed sitosterolemia:

Plasma lipoprotein profile and plasma cholesterol levels should be obtained. The cholesterol level may be elevated or normal (in approximately 50% of patients). Many of the common assays for cholesterol level do not differentiate between cholesterol and plant sterols. Normally, cholesterol represents more than 99% of plasma sterols. Approximately 0.2% of plasma sterols is cholestanol, and another 0.2% is plant sterols. In sitosterolemia, cholesterol represents approximately 80% of total plasma sterols and plant sterols represent approximately 20%.

Blood plant sterol levels are ascertained by gas-liquid chromatography (GLC), gas chromatography/mass spectrometry (GC/MS), or high-pressure liquid chromatography (HPLC). Plant sterols, especially sitosterol, and the 5-alpha derivatives of plant sterols are dramatically elevated in patients with sitosterolemia. A cutoff value of sitosterol 10 μg/ml typically discriminates patients with genetically confirmed sitosterolemia, although heterozygotes may exhibit sitosterol level greater than 10 μg/ml. Care must be taken when evaluating infants because infants taking commercial formulas with large amounts of vegetable oil may have elevated sitosterol levels (≤ 9 mg/dL according to the literature, and ≥ 13 mg/dL based on personal experience).

Children with parenteral nutrition-associated cholestasis may have plasma concentrations of plant sterols as high as those seen in patients with hereditary sitosterolemia (ie, total plant phytosterols of 1.3-1.8 mmol/L). Intralipid typically contains cholesterol, sitosterol, campesterol, and stigmasterol, the latter 3 of which are plant sterols. Adults receiving parenteral nutrition may also have elevated plasma plant sterol levels.^[29]

Chromatographic analysis of sterols is the only reliable diagnostic test for this condition; however, with the recent identification of the disease genes (ie, ABCG8, ABCG5), molecular diagnosis is now possible and useful in diagnostic confirmation. Next-generation sequencing can prove useful in differentiating sitosterolemia from other conditions when hyperlipidemia and/or xanthomas are present.^[30]

CBC count is indicated. Hemolytic anemia, either chronic or episodic, and sometimes with stomatocytosis may be present; platelet abnormalities, such as thrombocytopenia especially macrothrombocytopenia, are sometimes encountered.^[31]

Liver function testing is indicated.

Imaging Studies

Coronary angiography may be useful in select cases.

Procedures

Once sitosterolemia is diagnosed, depending on the patient's age, coronary arteriography may be indicated.

Arteriography may reveal coronary artery stenosis.

Histologic Findings

Biopsies of xanthomas in patients with sitosterolemia contain increased levels of plant sterols.

Liver histology has been normal to date in reported cases.

The changes of atherosclerotic coronary artery disease are observed.

Treatment & Management

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