Summary
Cerebrotendinous xanthomatosis (CTX) is an inborn error of acid bile synthesis and storage of sterols with onset in early childhood. It is characterized by xanthomas of the Achilles and other tendons, juvenile cataracts, early atherosclerosis and progressive neurological disorder with cerebellar ataxia beginning after puberty, systemic spinal cord involvement and dementia. Intelligence is low to normal. Large deposits of cholesterol and cholestanol are found in virtually every tissue, particularly Achilles tendon, brain, and lungs. The disease is caused by mutations in the sterol 27-hydroxylase gene (CYP27), a mitochondrial cytochrome P-450, which hydroxylates a variety of sterols at the C27 position in association with two protein cofactors, adrenodoxin and adrenodoxin reductase. Sterol 27-hydroxylase catalyzes the first step in the oxidation of the side chain of sterol intermediates in the bile acid synthesis pathway. Patients have a defect in bile acids synthesis. Cholestanol, the 5-alpha-dyhydro derivative of cholesterol, is enriched relative to cholesterol in all tissues. Diagnosis is made on the basis of abnormal amounts of cholestanol in the serum and tendons. Plasma cholesterol may be low or normal in patients. Treatment with cholic acid or chenodeoxycholic acid is indicated. Other treatments include the use of pravastatin (alpha HMG-CoA reductase inhibitor) or the combination of both chenodeoxycholic acid and pravastatin. *Author: Dr F. Palau (October 2003)*.
