Clinical and biochemical features, molecular diagnosis and long-term management of a case of cerebrotendinous xanthomatosis

• Published in: Clinica chimica acta Vol. 306; no. 1; pp. 63 - 69
• Main Authors: Burnett, John R, Moses, Esther A, Croft, Kevin D, Brown, Andrew J, Grainger, Keith, Vasikaran, Samuel D, Leitersdorf, Eran, Watts, Gerald F
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.04.2001; Elsevier
• Subjects: Achilles Tendon - metabolism; Adult; Biological and medical sciences; Cerebrotendinous xanthomatosis; Cholestanol - blood; Cholestanol - metabolism; Cholesterol - blood; Cholesterol - metabolism; Errors of metabolism; Female; Humans; Introns; Lipid Metabolism; Lipids - blood; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Molecular diagnosis; Serum cholestanol; Simvastatin - administration & dosage; Xanthomatosis, Cerebrotendinous - diagnosis; Xanthomatosis, Cerebrotendinous - genetics; Xanthomatosis, Cerebrotendinous - physiopathology; Xanthomatosis, Cerebrotendinous - therapy; Cerebrotendinous xanthomatosis; Molecular diagnosis; Serum cholestanol; Diseases of the osteoarticular system; Lipids; Enzymopathy; Vitamin D; Bile acid; Clinical biology; Genetics; Adult; Evolution; Female; Diagnosis; Human; Xanthomatosis; Nervous system diseases; Biochemical analysis; Enzyme; Deficiency; Simvastatin; Clinical form; Metabolic diseases; Exploration; Cholestanol derivatives; Long term; Genetic disease; Case study; Chemotherapy; Treatment; Cholestanetriol 26-monooxygenase; Oxidoreductases; Mutation; Molecular biology; Brain (vertebrata); Sterol; Tendon
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/S0009-8981(01)00391-6

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease characterised clinically by juvenile bilateral cataracts, progressive neurological dysfunction, and formation of tendon xanthomata. We describe the clinical and biochemical features, molecular diagnosis and long-term management of the first reported Australasian case of CTX. Molecular analysis confirmed the diagnosis of CTX and demonstrated that the patient was homozygous for a G→A transition in the splice donor site of intron 4 of the sterol 27-hydroxylase gene. Serum cholestanol concentrations were decreased with the HMG-CoA reductase inhibitor simvastatin alone and greater reductions were achieved after the addition of the bile acid chenodeoxycholic acid; suggesting a synergistic effect of this combination. Despite serum cholestanol concentrations remaining within the low-normal range, there has been no significant improvement in mental and physical abilities or in EEG abnormalities with 5 years of treatment. Metabolism of radiolabeled 7-ketocholesterol to aqueous soluble products was absent in CTX-derived macrophages. Consistent with this finding, plasma 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol concentrations were increased in the CTX subject compared with controls.