Disease relevance of Xanthomatosis, Cerebrotendinous

• The autosomal recessively inherited cholesterol metabolic disease, cerebrotendinous xanthomatosis (CTX), is caused by mutations in the sterol 27-hydroxylase gene [1].
• OBJECTIVES: Mutational analysis of the sterol 27-hydroxylase (CYP27) gene was performed on three patients from two Japanese families who had cerebrotendinous xanthomatosis (CTX) associated with parkinsonism [2].
• Here, we present the clinical, analytical and molecular features of a 36-years-old man who died from advanced ischaemic heart disease as a result of cerebrotendinous xanthomatosis (CTX), a rare condition characterized by elevation in plasma and most tissues of cholestanol and where neurological impairment is the hallmark of this disease [3].
• Cyclosporine-induced inhibition of the mitochondrial steroid 26-hydroxylase, an enzyme involved in the formation of bile acids from cholesterol and deficient in patients with cerebrotendinous xanthomatosis, may cause or contribute to the observed central nervous system toxicity [4].
• In order to elucidate the mechanism of xanthoma formation in cerebrotendinous xanthomatosis, mice were fed for 32 weeks with a diet rich in 5 alpha-cholestan-3 beta-ol (cholestanol) (1%, w/w) [5].

High impact information on Xanthomatosis, Cerebrotendinous

• In cerebrospinal fluid from untreated patients with cerebrotendinous xanthomatosis, immunoreactive apolipoprotein B or apolipoprotein B fragment was increased about 100-fold and albumin about 3.5-fold; apolipoprotein AI, apolipoprotein D, and lecithin:cholesterol acyltransferase were 1.5 to 3 times more concentrated [6].
• Increased concentrations of cholestanol and apolipoprotein B in the cerebrospinal fluid of patients with cerebrotendinous xanthomatosis. Effect of chenodeoxycholic acid [6].
• Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid [7].
• Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin [8].
• Intravenous administration of the 7 alpha-3H- and 4-14C-labeled cholesterol to a patient with cerebrotendinous xanthomatosis (CTX) resulted in formation of cholestanol which had 70-75% lower 3H/14C ratio [9].

Chemical compound and disease context of Xanthomatosis, Cerebrotendinous

• Cholic acid biosynthesis: the enzymatic defect in cerebrotendinous xanthomatosis [10].
• The increased production of cholestanol in cerebrotendinous xanthomatosis may be accounted for by enhanced hepatic formation of 4-cholesten-3-one [11].
• The serum levels of 7 alpha-hydroxy-4-cholesten-3-one as well as those of cholesta-4,6-dien-3-one were found to be markedly elevated in the three patients with cerebrotendinous xanthomatosis [12].
• The sterol storage disorder cerebrotendinous xanthomatosis (CTX) is characterized by abnormal deposition of cholesterol and cholestanol in multiple tissues [13].
• In bile from 14 healthy subjects, the concentration was 0.14 +/- 0.01 micrograms/ml (mean +/- S.E.). Four bile samples collected from two patients with cerebrotendinous xanthomatosis contained considerably higher amounts of this steroid, 0.47-1.32 micrograms/ml [14].

Biological context of Xanthomatosis, Cerebrotendinous

• Evoked potentials in cerebrotendinous xanthomatosis and effect induced by chenodeoxycholic acid [15].
• Genetic analysis of patients with cerebrotendinous xanthomatosis has shown several genetic defects: 1) two different point mutations in which arginine codons were replaced by cysteine codons; 2) deletion of thymidine in exon 4; and 3) a guanosine to adenosine substitution at the 3' splice acceptor site of intron 4 of the gene [16].
• Exon skipping in the sterol 27-hydroxylase gene leads to cerebrotendinous xanthomatosis [17].
• We investigated the effect of the hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor lovastatin and the primary bile acid chenodeoxycholic acid (CDCA) on plasma sterol and bile alcohol concentrations and the excretion of bile alcohols in urine in a 38-year-old homozygote with cerebrotendinous xanthomatosis (CTX) [18].

Anatomical context of Xanthomatosis, Cerebrotendinous

• Feces from normal subjects and patients with cerebrotendinous xanthomatosis were incubated anaerobically with labeled chenodeoxycholic acid and ursodeoxycholine acid for known periods, and the bile acids formed were analyzed by TLC and scintillation counting [19].
• Moreover, [(3)H]27OH-7K was produced by human monocyte-derived macrophages (HMDMs) supplied with [(3)H]7K but not in HMDMs from a patient with cerebrotendinous xanthomatosis (CTX) shown to have a splice-junction mutation of sterol 27-hydroxylase [20].
• The cholesterol and cholestanol biosynthetic pathways and the control of cholesterolgenesis were investigated in skin fibroblasts, from patients with cerebrotendinous xanthomatosis (CTX) and from normal subjects, growth in a lipoprotein deficient (d less than 1.25 g/ml) medium [21].
• PURPOSE: To describe the CT and MR findings in the brain and spinal cord of patients with cerebrotendinous xanthomatosis and to seek possible correlations between clinical, biochemical (cholestanol levels), and neuroimaging findings [22].
• A search of MEDLINE, using the keywords cerebrotendinous xanthomatosis, brain xanthoma, tendon xanthoma, cholestanol, cholesterol and bile alcohol for articles covering clinical manifestations, laboratory findings, pathology, molecular defects and treatment of CTX, revealed 175 patients with documented CTX [23].

Gene context of Xanthomatosis, Cerebrotendinous

• CYP27A1 seems, however, to have roles beyond this, as illustrated by patients with a deficient sterol 27-hydroxylase due to mutations of the CYP27A1 gene [cerebrotendinous xanthomatosis (CTX)] [24].
• Cerebrotendinous xanthomatosis (CTX), sterol 27-hydroxylase (CYP27A1) deficiency, is associated with markedly reduced chenodeoxycholic acid (CDCA), the most powerful activating ligand for farnesoid X receptor (FXR) [25].
• This explains why humans are more susceptible to sterol accumulation and suggests that synthetic ligands for human PXR could be used to treat cerebrotendinous xanthomatosis and other disorders of cholesterol excess [26].
• The accumulation of various 25-hydroxylated C(27)-bile alcohols in blood and their excretion in urine are characteristic features of cerebrotendinous xanthomatosis (CTX) a recessively inherited inborn error of bile acid synthesis caused by mutations in the mitochondrial sterol 27-hydroxylase (CYP27) gene [27].
• Study of a family with Cerebrotendinous Xanthomatosis. No HLA linkage, but an informative recombination between HLA-B and Bf [28].

Analytical, diagnostic and therapeutic context of Xanthomatosis, Cerebrotendinous

• Effect of chenodeoxycholic acid on biliary and urinary bile acids and bile alcohols in cerebrotendinous xanthomatosis; monitoring by high performance liquid chromatography [29].
• The identification of a major biliary and plasma bile alcohol glucuronide, 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 25-tetrol-3-0-beta-D-glucuronide, present in cerebrotendinous xanthomatosis (CTX) patients, was investigated by positive ion fast atom bombardment mass spectrometry (FAB-MS) [30].
• Potential application of thin-layer chromatography and thin-layer chromatography with flame ionization detection of cholestanol in the diagnosis of cerebrotendinous xanthomatosis [31].
• Simplified determination of cholestanol in serum by gas-liquid chromatography: biochemical diagnosis of cerebrotendinous xanthomatosis [32].
• Reduction of urinary bile alcohol excretion and serum cholestanol in patients with cerebrotendinous xanthomatosis after oral administration of deoxycholic acid [33].

References