Cerebrotendinous xanthomatosis; Van Bogaert-Scherer-Epstein, disease ... (Cerebrotendinous xanthomatosis; Van Bogaert-Scherer-Epstein Disease) - Gen CYP27A1

Xanthomatosis cerebrotendinous (CTX), also known as Van Bogaert-Scherer-Epstein disease is a metabolic disease caused by an alteration of lipid storage. Those affected can not metabolize some lipids, such as cholesterol, so this or some of its metabolites accumulate in various parts of the body. Xanthomatosis indicates the formation of yellow fat nodules (xanthomas) and Cerebrotendinous indicates the presence of xanthomas in the brain and tendons.

Patients also manifest chronic diarrhea since childhood, early cataracts, cholestasis, prone to fracture, nerve problems (peripheral neuropathy, dementia, depression, seizures, hallucinations, ...), difficulty with motor coordination (ataxia) brittle bones , and speech (dysarthria). Tendon xanthomas, such as Achilles tendon can cause discomfort and interfere with tendon flexibility. In addition, they are more likely to develop cardiovascular disease or respiratory failure due to lipid accumulation in the heart or lungs, respectively. Xanthomas can accumulate in myelin, causing destruction and disruption of nerve signals in the brain. Atrophy of brain tissue due to excessive excess lipid deposits also contributes to neurological problems. Those affected die, usually in the fourth or fifth decade of life as a result of progressive neurological deterioration, pseudobulbar palsy or acute myocardial infarction.

This process is due to mutations in the CYP27A1 gene (cytochrome P450 family subfamily A member 27 1), located on the long arm of chromosome 2 (2q35). This gene belongs to the family of the "citocronmo P450" genes. The gene encoding the enzyme CYP27A1 "sterol 27-hydroxylase", found in mitochondria, where cholesterol is metabolized to bile acids used in the digestion of fats. Sterol 27-hydroxylase enzyme plays a key role in maintaining normal levels of cholesterol in the body.

They have identified at least 90 mutations in this gene associated with cerebrotendinous xanthomatosis development, some of which correspond to: missense mutations (43), and cutting mutations -splicing- junction (17), small deletions (13) , small insertions (2), small insertions / deletions (2), larger deletions (1) and complex rearrangements (1). Most CYP27A1 gene mutations in amino acid changes consist enzyme 27-hydroxylase. The most common is the R362C, wherein the amino acid arginine is replaced by the amino acid cysteine at position 362 of the enzyme. Changes in amino acids normally disrupt the normal function of the protein and alters its ability to break down cholesterol. Other mutations in the CYP27A1 gene, inhibit protein coding. Being affected cholesterol metabolism, it accumulates in the form of a similar molecule, cholestanol, which is present in the xantomas, blood and brain. However, cholesterol is not elevated in blood. Accumulations of cholesterol and cholestanol in the brain and tendons, or other tissues, give name to the process.

The clinical and laboratory diagnosis of Cerebrotendinous xanthomatosis can be difficult, since the biochemical analysis of blood and urine may be normal. Early diagnosis is important to stop the progression of the disease and partially reverse its manifestations.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform mutation detection cerebrotendinous xanthomatosis associated with, using the complete PCR amplification of the exons of CYP27A1 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).