Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis

Christie M. Ballantyne, Gloria L Vega, Cara East, Glen Richards, Scott M Grundy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Cerebrotendinous xanthomatosis (CTX) is a rare disorder characterized by a defect in conversion of cholesterol into bile acids, increased plasma levels of cholestanol, and accumulations of sterols in tendons, brain, and coronary arteries. Despite the presence of tendon xanthomas, patients with CTX frequently have low levels of plasma cholesterol and low density lipoproteins (LDL). The mechanisms for a low LDL are not understood. The present study, therefore, was carried out to examine the metabolism of LDL in a 58-year-old black man with CTX. This particular patient had an LDL-cholesterol in the mid-normal range (149 ± 6 mg/dL). Nonetheless, his fractional catabolic rate (FCR) for LDL-apolipoprotein (apo-LDL) was 0.45 pools/d, which was increased compared to 15 aged-matched men (FCR, 0.30 ± 0.01 pools/d). His production rate for apo-LDL (18.5 mg/kg-d) also was increased compared to those of middle-aged men (13.5 ± 2.5 mg/kg-d). Since the underlying defect in CTX can be reversed by administration of chenodeoxycholic acid (chenodiol), the patient was treated with chenodiol (250 mg 4 × daily), and measurements of LDL kinetics were repeated. During chenodiol therapy, his LDL-cholesterol concentration rose significantly to 165 ± 12 mg/dL; his FCR for apo-LDL fell to 0.29 pools/d; and his production rate of apo-LDL declined to 14.4 mg/kg-d. We postulate that chenodiol suppressed the excessive synthesis of cholesterol and bile acids, which had two effects. It curtailed both the overproduction of LDL and the excessive synthesis of LDL receptors, the latter being responsible for the high FCR of apo-LDl in the untreated state.

Original languageEnglish (US)
Pages (from-to)270-276
Number of pages7
JournalMetabolism
Volume36
Issue number3
DOIs
StatePublished - 1987

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Cerebrotendinous Xanthomatosis
LDL Lipoproteins
Chenodeoxycholic Acid
LDL Cholesterol
Bile Acids and Salts
Tendons
Cholestanol
Cholesterol
Xanthomatosis
Apolipoproteins
LDL Receptors
Sterols
Coronary Vessels
Reference Values

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis. / Ballantyne, Christie M.; Vega, Gloria L; East, Cara; Richards, Glen; Grundy, Scott M.

In: Metabolism, Vol. 36, No. 3, 1987, p. 270-276.

Research output: Contribution to journalArticle

Ballantyne, Christie M. ; Vega, Gloria L ; East, Cara ; Richards, Glen ; Grundy, Scott M. / Low-density lipoprotein metabolism in cerebrotendinous xanthomatosis. In: Metabolism. 1987 ; Vol. 36, No. 3. pp. 270-276.
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abstract = "Cerebrotendinous xanthomatosis (CTX) is a rare disorder characterized by a defect in conversion of cholesterol into bile acids, increased plasma levels of cholestanol, and accumulations of sterols in tendons, brain, and coronary arteries. Despite the presence of tendon xanthomas, patients with CTX frequently have low levels of plasma cholesterol and low density lipoproteins (LDL). The mechanisms for a low LDL are not understood. The present study, therefore, was carried out to examine the metabolism of LDL in a 58-year-old black man with CTX. This particular patient had an LDL-cholesterol in the mid-normal range (149 ± 6 mg/dL). Nonetheless, his fractional catabolic rate (FCR) for LDL-apolipoprotein (apo-LDL) was 0.45 pools/d, which was increased compared to 15 aged-matched men (FCR, 0.30 ± 0.01 pools/d). His production rate for apo-LDL (18.5 mg/kg-d) also was increased compared to those of middle-aged men (13.5 ± 2.5 mg/kg-d). Since the underlying defect in CTX can be reversed by administration of chenodeoxycholic acid (chenodiol), the patient was treated with chenodiol (250 mg 4 × daily), and measurements of LDL kinetics were repeated. During chenodiol therapy, his LDL-cholesterol concentration rose significantly to 165 ± 12 mg/dL; his FCR for apo-LDL fell to 0.29 pools/d; and his production rate of apo-LDL declined to 14.4 mg/kg-d. We postulate that chenodiol suppressed the excessive synthesis of cholesterol and bile acids, which had two effects. It curtailed both the overproduction of LDL and the excessive synthesis of LDL receptors, the latter being responsible for the high FCR of apo-LDl in the untreated state.",
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AB - Cerebrotendinous xanthomatosis (CTX) is a rare disorder characterized by a defect in conversion of cholesterol into bile acids, increased plasma levels of cholestanol, and accumulations of sterols in tendons, brain, and coronary arteries. Despite the presence of tendon xanthomas, patients with CTX frequently have low levels of plasma cholesterol and low density lipoproteins (LDL). The mechanisms for a low LDL are not understood. The present study, therefore, was carried out to examine the metabolism of LDL in a 58-year-old black man with CTX. This particular patient had an LDL-cholesterol in the mid-normal range (149 ± 6 mg/dL). Nonetheless, his fractional catabolic rate (FCR) for LDL-apolipoprotein (apo-LDL) was 0.45 pools/d, which was increased compared to 15 aged-matched men (FCR, 0.30 ± 0.01 pools/d). His production rate for apo-LDL (18.5 mg/kg-d) also was increased compared to those of middle-aged men (13.5 ± 2.5 mg/kg-d). Since the underlying defect in CTX can be reversed by administration of chenodeoxycholic acid (chenodiol), the patient was treated with chenodiol (250 mg 4 × daily), and measurements of LDL kinetics were repeated. During chenodiol therapy, his LDL-cholesterol concentration rose significantly to 165 ± 12 mg/dL; his FCR for apo-LDL fell to 0.29 pools/d; and his production rate of apo-LDL declined to 14.4 mg/kg-d. We postulate that chenodiol suppressed the excessive synthesis of cholesterol and bile acids, which had two effects. It curtailed both the overproduction of LDL and the excessive synthesis of LDL receptors, the latter being responsible for the high FCR of apo-LDl in the untreated state.

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