In CTX the breakdown of cholesterol to cholic acid and chenodeoxycholic acid is blocked by a marked reduction in sterol 27-hydroxylase activity. 7-alpha-4-cholesten-3-one accumulates and is broken down to 25-hydroxylated bile alcohol or cholestanol
Laboratory testing may involve:
(1) plasma cholestanol concentration in µg/dL, with ratio to upper limit of normal (ULN)
(2) plasma bile alcohol concentration in nmol/L, with ratio to upper limit of normal (ULN)
(3) urine bile alcohol concentration in nmol/L
(4) sterol 27-hydroxylase activity in leukocytes (a mitochondrial enzyme, may not be readily available)
(5) serum cholesterol in mg/dL, with ratio to upper limit of normal (ULN)
(6) plasma 5-alpha-cholestanol concentration
(7) chenodeoxycholic acid
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Laboratory Finding
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Findings in CTX
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ratio of plasma cholestanol to ULN
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>= 5
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ratio of bile alcohol concentration to ULN
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>= 500
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urine bile alcohol concentration
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> 10,000 nmol/L (usually undetectable)
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sterol 27-hydroxylase activity, with production of chenodeoxycholic acid
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markedly reduce
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serum cholesterol ratio to ULN
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< 1
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plasma 5-alpha-cholestanol ratio to ULN
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> 1
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Other causes of xanthomas often have an elevated serum cholesterol concentration.
Therapy with chenodeoxycholic acid reduces synthesis of bile acid and the accumulation of cholestanol.
