What is the mortality and morbidity associated with sitosterolemia (phytosterolemia)?

Updated: May 24, 2019
  • Author: Robert D Steiner, MD; Chief Editor: Luis O Rohena, MD, MS, FAAP, FACMG  more...
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Little toxicity occurs, and no obvious adverse effects are associated with phytosterols in healthy individuals. However, when individuals have sitosterolemia, they have significant morbidity and increased risk for premature mortality. Coronary heart disease and its inherent health consequences are the primary causes of illness and premature death in patients with sitosterolemia.

Xanthomas occur most prominently in the extensor tendons of the hands and Achilles tendon. They can cause significant discomfort, interfere with mobility, and have cosmetic implications. One case of spinal cord compression secondary to multiple intradural extramedullary xanthomas has been reported.

Males with sitosterolemia have a high prevalence of accelerated atherosclerosis leading to coronary heart disease and subsequent premature death. The high content of plant sterols in the circulatory lipoproteins has been postulated to possibly promote their deposition in the arterial walls. Deaths have been reported in adolescent males as young as 13 years caused by coronary arthrosclerosis and secondary infarction. Angina pectoris has been reported in a 12-year-old girl.

Hemolysis and platelet abnormalities, including thrombocytopenia, have been described. Ezetimibe ameliorates the effect on platelets. [10] Episodic hemolysis has been reported in several patients. Stomatocytes and giant platelets may be seen. [11] Erythrocytes have been shown to contain increased amounts of sitosterol, rendering the cell membrane more rigid and, therefore, more prone to lysis and rupture.

The clinical, biochemical, and molecular genetic features (mainly manifested by hematologic abnormalities) of a Chinese family with sitosterolemia were reported. [12] The main clinical features of these patients were hemolysis and macrothrombocytopenia. The authors suggested that blood cells could be a target for the toxic effect of plant sterols in blood. Another report of a case with macrothrombocytopenia, stomatocytic hemolysis, and splenomegaly without other obvious features of the condition was described. [13]

Arthralgias and arthritis can occur particularly in the knee and ankle joints.

Trace amounts of unsaturated plant sterols and cholesterol have been found in the brain tissue of people with sitosterolemia. The only identified neurological complication to date is one reported case of paraplegia secondary to spinal cord compression by multiple intradural extramedullary xanthomas.

In patients with sitosterolemia, 5α-stanol accumulation may be associated with thyroid function. Ezetimibe reduces circulating 5α-stanol levels while increasing levels of FT3/FT4, implying increased conversion of T4 to T3, thus possibly improving thyroid hormone status. [14]

Abnormal liver function test results can be observed, and liver cirrhosis has been reported [15] at least once with successful treatment by liver transplant. [16] Heterozygotes are likely healthy, [17] although an elevated plasma plant sterol concentration of 3.07 mg/dL was found in one heterozygote. [18]

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