Submitted on March 7, 2006
Revised on September 29, 2006
Accepted on October 1, 2006
Cholestanol metabolism in patients with cerebrotendinous xanthomatosis: Absorption, turnover, tissue deposition and clues to pathological consequences
Ashim K. Bhattacharyya, Don S. Lin, and William E. Connor
Medicine/Clinical Nutrition, Oregon Health & Science University, PORTLAND, OR 97239
Corresponding Author: connorw{at}ohsu.edu
To study the metabolism of cholestanol in patients with cerebrotendinous xanthomatosis (CTX), we measured the cholestanol absorption, cholesterol and cholestanol turnover and the tissue content of sterols in two patients. Cholestanol absorption was about 5.0 percent. The rapid exchangeable pool of cholestanol was 233 mg, and the total exchangeable pool was 752 mg. The production rate of cholestanol in pool A was 39 mg/day. Cholestanol 4-C14 was detected in the xanthomas but neither 4-C14 cholestanol or 4-C14 cholesterol was detected in peripheral nerves biopsied 49 and 97 days after 4-14C-cholesterol given intravenously. Of the eighteen tissues analyzed at biopsy and autopsy, the cholestanol content varied from 0.09 mg/gm in psoas muscle to 76 mg/gm in a cerebellar xanthoma. With the assumption that cholestanol to cholesterol ratio is 1.0, the relative cholestanol to cholesterol ratio varied from 1.0 in plasma and liver to 30.0 in the cerebellar xanthoma; cholestanol was especially high in nerve tissue. Our data indicated that CTX patients absorb cholestanol from the diet. They have a higher than normal cholestanol production rate. Cholestanol was derived from cholesterol. In CTX patients, the blood-brain barrier was intact to the passage of 4-14C cholesterol and 4-14C cholestanol. The deposition of large amounts of cholestanol (up to 30 percent of total sterols in cerebellum) in nervous tissues must have an important role in the neurological symptoms in CTX patients. In view of the intact blood-brain barrier, several other explanations for the large amounts of cholestanol in the brain were postulated.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
