Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study.

BACKGROUND AND AIM: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. METHODS AND RESULTS: Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. CONCLUSION: Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. CLINICAL TRIAL NUMBER: ISRCTN35739639.

High DHEAS in girls and metabolic features throughout pubertal maturation.

CONTEXT: An association between premature adrenarche and metabolic syndrome at presentation has been described. Our aim was to assess whether the presence of high dehydroepiandrosterone sulphate (DHEAS [HD]) at the adrenarche determines the risk of metabolic syndrome during puberty, taking into account body mass index (BMI) and birth weight. DESIGN: Prospective observational. PATIENTS: Five hundred four girls from the Growth and Obesity Chilean Cohort Study were followed from birth through puberty. At age ~7, subjects were classified by DHEAS concentrations into the HD (>75th percentile) or normal DHEAS (ND, ≤75th percentile) subgroups. MEASUREMENTS: Anthropometrics, semiannual clinical pubertal staging and hormonal and metabolic levels. The relationships among DHEAS at age ~7, metabolic syndrome, and each of its components independently, were analyzed by linear and logistic regression models during puberty and 1-year postmenarche, adjusted by confounders. RESULTS: Girls with HD at 7 years exhibited higher BMI, more central fat and higher serum androgen and insulin like growth factor (IGF)-I levels throughout puberty. Also, girls with HD had a greater prevalence of hyperglycemia at B2 and B4 breast stages, and of low HDL at B4. At 1 year after menarche, HD girls had a higher prevalence of metabolic syndrome, and those with BMI > 1 SD score had a higher metabolic score and insulin levels than ND girls with similar BMI. CONCLUSIONS: Our observations suggest that girls with HD at the age of adrenarche may be at greater risk for metabolic syndrome at adolescence, especially in those who are overweight or obese. Our results emphasize the importance of lifestyle interventions for childhood overweight and obesity among girls with HD.

A replication study of JTC bias, genetic liability for psychosis and delusional ideation.

BACKGROUND: This study attempted to replicate whether a bias in probabilistic reasoning, or 'jumping to conclusions'(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation. METHODS: Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses. RESULTS: JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46-5.17 for siblings and aRR: 5.07 CI 95% 4.13-6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67-8.51, and in patients: 2.15 CI 95% 0.94-4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences. CONCLUSIONS: These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

BACKGROUND: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study.

BACKGROUND AND AIMS: Adipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. METHODS AND RESULTS: Among Hispanic/Latino participants (N = 537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (ß (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (ß (SE): -0.31 (0.06) for females; -0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (ß (SE): 0.12 (0.04) for both females and males). CONCLUSION: We observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

Mental Disorder Diagnosis from EEG Signals Employing Automated Leaning Procedures Based on Radial Basis Functions.

Purpose: In this paper, a new automated procedure based on deep learning methods for schizophrenia diagnosis is presented. Methods: To this aim, electroencephalogram signals obtained using a 32-channel helmet are prominently used to analyze high temporal resolution information from the brain. By these means, the data collected is employed to evaluate the class likelihoods using a neuronal network based on radial basis functions and a fuzzy means algorithm. Results: The results obtained with real datasets validate the high accuracy of the proposed classification method. Thus, effectively characterizing the changes in EEG signals acquired from schizophrenia patients and healthy volunteers. More specifically, values of accuracy better than 93% has been obtained in the present research. Additionally, a comparative study with other approaches based on well-knows machine learning methods shows that the proposed method provides better results than recently proposed algorithms in schizophrenia detection. Conclusion: The proposed method can be used as a diagnostic tool in the detection of the schizophrenia, helping for early diagnosis and treatment.

Novel loci and Mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys.

Puberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height. However, they do not capture many genetic loci involved in growth changes over distinct growth phases. Further, such GWAS have been mostly performed in Europeans, but it is unknown how these findings relate to other continental populations. In this study, we analyzed the genetic basis of three pubertal traits; namely, peak height velocity (PV), age at PV (APV) and height at APV (HAPV). We analyzed a cohort of 904 admixed Chilean children and adolescents with European and Mapuche Native American ancestries. Height was measured on roughly a [Formula: see text]month basis from childhood to adolescence between 2006 and 2019. We predict that, in average, HAPV is 4.3 cm higher in European than in Mapuche adolescents (P = 0.042), and APV is 0.73 years later in European compared with Mapuche adolescents (P = 0.023). Further, by performing a GWAS on 774, 433 single-nucleotide polymorphisms, we identified a genetic signal harboring 3 linked variants significantly associated with PV in boys (P [Formula: see text]). This signal has never been associated with growth-related traits.

Eating behavior and body composition in Chilean young adults.

BACKGROUND: Notable weight gain is observed during young adulthood, compared to other adult age groups, yet the relation between eating behavior and body composition at this stage remains poorly understood. OBJECTIVE: The aim of this cross-sectional study was to assess the association between eating behavior scores (cognitive restraint, uncontrolled eating, and emotional eating), and body composition in a sample of Chilean young adults. METHODS: Logistic and linear regression models assessed the independent associations between cognitive restraint, uncontrolled eating, and emotional eating, derived from the Three Factor Eating Questionnaire-R18, and body mass index (BMI), percent body fat by dual-energy X-ray absorptiometry, and central obesity, accounting for demographic covariates, stratified by sex, in a sample of 555 participants of the Santiago Longitudinal Study (mean age 22.6 years [SD 0.4]). RESULTS: Cognitive restraint was positively associated with obesity, defined by BMI, % body fat, and central obesity. Emotional eating was related to obesity, defined by % body fat and central obesity in men and women and to obesity, defined by BMI, in women. Cognitive restraint was related to BMI in men and % body fat in women. Uncontrolled eating was not associated with adiposity in men or women. CONCLUSIONS: In Chilean young adults, cognitive restraint and emotional eating scores were associated with higher BMI, elevated percent body fat, and greater central obesity.

Association between indicators of systemic inflammation biomarkers during puberty with breast density and onset of menarche.

BACKGROUND: Systemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. Pubertal development presents a critical window of breast tissue susceptibility to exogenous and endogenous factors, including pro-inflammatory markers. However, little is known about the role of systemic inflammation on adolescent breast composition and pubertal development among girls. METHODS: We investigated associations between circulating levels of inflammatory markers (e.g., interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNFR2), and C-reactive protein (CRP)) at Tanner stages 2 and 4 and breast composition at Tanner stage 4 in a cohort of 397 adolescent girls in Santiago, Chile (Growth and Obesity Cohort Study, 2006-2018). Multivariable linear models were used to examine the association between breast composition and each inflammatory marker, stratifying by Tanner stage at inflammatory marker measurement. Accelerated failure time models were used to evaluate the association between inflammatory markers concentrations at each Tanner stage and time to menarche. RESULTS: In age-adjusted linear regression models, a doubling of TNFR2 at Tanner 2 was associated with a 26% (95% CI 7-48%) increase in total breast volume at Tanner 4 and a 22% (95% CI 10-32%) decrease of fibroglandular volume at Tanner 4. In multivariable models further adjusted for body fatness and other covariates, these associations were attenuated to the null. The time to menarche was 3% (95% CI 1-5%) shorter among those in the highest quartile of IL-6 at Tanner 2 relative to those in the lowest quartile in fully adjusted models. Compared to those in the lowest quartile of CRP at Tanner 4, those in the highest quartile experienced 2% (95% CI 0-3%) longer time to menarche in multivariable models. CONCLUSIONS: Systemic inflammation during puberty was not associated with breast volume or breast density at the conclusion of breast development among pubertal girls after adjusting for body fatness; however, these circulating inflammation biomarkers, specifically CRP and IL-6, may affect the timing of menarche onset.

Early Obesity: Risk Factor for Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), defined as fat accumulation greater than 5% in hepatocytes, may progress to fibrosis or cirrhosis later in life. NAFLD prevalence in adolescents has increased significantly in direct relation with obesity prevalence. Fatty liver has become the most frequent indication for liver transplantation in adults. OBJECTIVE: The aim of the study was to identify anthropometric variables during the first 10 years of life associated to the risk of developing NAFLD in adolescence. METHODS: Longitudinal cohort study 'Growth and Obesity Chilean Cohort Study' (GOCS) consisting of 513 children born in 2002 to 2003, with yearly anthropometric data collected over a 10-year period. The presence of intrahepatic fat in the livers of subjects 14 to 16 years of age was determined using abdominal ultrasound. In addition, elastography was performed on all participants with ultrasound evidence of NAFLD. RESULTS: 9.7% of the participants presented findings compatible with NAFLD. After 2 years of age, obesity significantly and progressively increased the probability of NAFLD occurrence in adolescence. Obesity at 5 years of age was associated with the highest OR for NAFLD, reaching values of 8.91 (95% CI 3.03-16.11). Among participants with NAFLD, those with altered liver elasticity (≥7 kPa) had greater weight, BMI z-score, waist and hip circumference, and altered liver enzymes (P < 0.05). CONCLUSION: The risk of developing NAFLD in adolescence increases progressively with early obesity starting at age 2 years.

Microstructure of starch-based meals with either palm or soybean oils alter in vitro starch digestibility with no major effects on glycaemic responses.

Glycaemic response (GR) to starch-based meals depends on their food composition and microstructure. We studied the effect of palm and soybean oils on the microstructure of a solid starch-oil-gluten matrix, on the starch gelatinisation and in vitro digestibility. Additionally, a pilot cross-over study was carried out to assess GR after eating gelatinised starch/gluten-based foods with the addition of either palm or soybean oil in 8 young non-diabetic female volunteers (ISRCTN39636850). Both types of foods generated similar starch gelatinisation temperature. Starch/gluten-based food with soybean oil had rougher microstructure compared to food with palm oil, showing a higher initial and lower final in vitro digestion. Administration of starch/gluten-based meals with either palm or soybean oils to volunteers show very similar postprandial glucose or insulin responses. In conclusion, differences in fatty acid composition changes food microstructure and in vitro starch digestibility, with no major effects on glycaemic responses in female volunteers.

Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia.

BACKGROUND: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. METHODS: An adult female proband with hypoalphalipoproteinemia, corneal opacity and mild anemia, as well as her first-degree relatives, were recruited for clinical, biochemical, genetic, in-silico and in-vitro LCAT analysis. Sequencing of exons and intron-exon boundaries was performed to identify mutations. Site-directed mutagenesis was carried out to generate plasmids containing cDNA with wild type or mutant sequences. Such expression vectors were transfected to HEK-239 T cells to asses the effect of LCAT variants in expression, synthesis, secretion and enzyme activity. In-silico prediction analysis and molecular modeling was also used to evaluate the effect of LCAT variants. RESULTS: LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband's plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. CONCLUSION: Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p.V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.

Propagation of vibrational modes in classical harmonic lattice with correlated disorder.

The vibrational modes with nonzero frequency are localized in harmonic lattice with disordered masses. In our work, we investigated numerically the propagation of vibrational energy in harmonic lattice with long-range correlated disordered masses, which are randomly distributed with power law spectrum S ( k ) ∝ k - α . For α = 0, a standard uncorrelated disordered mass distribution was observed and for α > 0 its distribution exhibits intrinsic long-range correlations. Our procedure was done by the numerical solution of the classical equations for the mass displacement and velocities. Energy flow was investigated after injection of an initial wave-packet with energy E0 and the dynamics of the vibrational energy wave-packet was analyzed. We also investigated the dynamics of a pulse pumped at one side of the lattice. Our calculations suggest that vibrational modes with nonzero frequency propagate within harmonic lattice with correlated disordered masses distribution.

Insulin Sensitivity Is Associated with Lipoprotein Lipase (LPL) and Catenin Delta 2 (CTNND2) DNA Methylation in Peripheral White Blood Cells in Non-Diabetic Young Women.

Hyperglycaemia and type 2 diabetes (T2D) are associated with impaired insulin secretion and/or insulin action. Since few studies have addressed the relation between DNA methylation patterns with elaborated surrogates of insulin secretion/sensitivity based on the intravenous glucose tolerance test (IVGTT), the aim of this study was to evaluate the association between DNA methylation and an insulin sensitivity index based on IVGTT (calculated insulin sensitivity index (CSi)) in peripheral white blood cells from 57 non-diabetic female volunteers. The CSi and acute insulin response (AIR) indexes, as well as the disposition index (DI = CSi × AIR), were estimated from abbreviated IVGTT in 49 apparently healthy Chilean women. Methylation levels were assessed using the Illumina Infinium Human Methylation 450k BeadChip. After a statistical probe filtering, the two top CpGs whose methylation was associated with CSi were cg04615668 and cg07263235, located in the catenin delta 2 (CTNND2) and lipoprotein lipase (LPL) genes, respectively. Both CpGs conjointly predicted insulin sensitivity status with an area under the curve of 0.90. Additionally, cg04615668 correlated with homeostasis model assessment insulin-sensitivity (HOMA-S) and AIR, whereas cg07263235 was associated with plasma creatinine and DI. These results add further insights into the epigenetic regulation of insulin sensitivity and associated complications, pointing the CTNND2 and LPL genes as potential underlying epigenetic biomarkers for future risk of insulin-related diseases.

Interactions between Starch, Lipids, and Proteins in Foods: Microstructure Control for Glycemic Response Modulation.

In real food, starch is usually forming part of a matrix with lipids and proteins. However, research on this ternary system and interactions between such food components has been scarce so far. The control of food microstructure is crucial to determine the product properties, including sensorial and nutritionals ones. This paper reviews the microstructural principles of interactions between starch, lipids, and proteins in foods as well as their effect on postprandial glycemic response, considering human intrinsic differences on postprandial glycemic responses. Several lines of research support the hypothesis that foods without rapidly digestible starch will not mandatorily generate the lowest postprandial glycemic response, highlighting that the full understanding of food microstructure, which modulates starch digestion, plays a key role on food design from a nutritional viewpoint.

Fabry-Perot cavity based on silica tube for strain sensing at high temperatures.

In this work, a Fabry-Perot cavity based on a new silica tube design is proposed. The tube presents a cladding with a thickness of ~14 µm and a hollow core. The presence of four small rods, of ~20 µm diameter each, placed in diametrically opposite positions ensure the mechanical stability of the tube. The cavity, formed by splicing a section of the silica tube between two sections of single mode fiber, is characterized in strain and temperature (from room temperature to 900 °C). When the sensor is exposed to high temperatures, there is a change in the response to strain. The influence of the thermal annealing is investigated in order to improve the sensing head performance.

Preventive letter: doubling the return rate after gestational diabetes mellitus.

To measure the impact of a "Preventive Letter" designed to encourage the return of gestational diabetes mellitus (GDM) mothers to follow up visit after delivery, in the context of a worldwide concern about low return rates after delivery of these patients. Mothers with GDM require medical evaluation and an oral glucose tolerance test (OGTT) 6 weeks after delivery, in order to: [a] confirm remission of GDM and [b] provide advice on the prevention of type 2 diabetes. In the year 2003 we developed a "Preventive Letter", containing three aspects: [a] current treatment, [b] suggested management during labor, and [c] a stapled laboratory order for OGTT to be performed 6 weeks after delivery. The return rate after delivery was assessed in two groups of GDM mothers: [a] "Without Preventive Letter" (n = 253), and "With Preventive Letter" (n = 215). Both groups, similar with respect to age (33.0 ± 5.4 and 32.3 ± 4.9 years respectively, p = 0.166) and education time (14.9 ± 1.8 and 15.0 ± 1.8 years respectively, p = 0.494), showed a significant difference in the 1-year return rate after delivery, as assessed by the Kaplan-Meier test: 32.0 % for the group "Without Preventive Letter", and 76.0 % for the group "With Preventive Letter" (p < 0.001). The 1-year return rate after delivery of GDM mothers was 2.4 times higher in the group "With Preventive Letter" than in the group without it. We believe that this low-cost approach could be useful in other institutions caring for pregnant women with diabetes.

Silica microspheres array strain sensor.

An optical fiber sensor based on arrays of silica microspheres is proposed. The microspheres are produced separately using a fusion splicer and then also connected in series by fusion splicing. Three different sensors are presented, differing by the number of microspheres. Due to the geometry of the structures, different behaviors are obtained in strain measurements. Sensors with an odd number of microspheres are more sensitive to strain than the ones with an even number of microspheres. Additionally, the sensing heads are subjected to temperature where a sensitivity of 20.3 pm/°C is obtained in a range of 200°C.

[Cerebrotendinous xanthomatosis: physiopathology, clinical manifestations and genetics]. / Xantomatosis cerebrotendinosa: aspectos fisiopatológicos, clínicos y genéticos.

Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease, caused by genetic deficiency of the 27-hydroxylase enzyme (encoded by CYP27A1). It plays a key role in cholesterol metabolism, especially in bile acid synthesis and in the 25-hydroxylation of vitamin D3 in the liver. Its deficiency causes reduced bile acid synthesis and tissue accumulation of cholestanol. Clinical manifestations are related to the presence of cholestanol deposits and include tendon xanthomas, premature cataracts, chronic diarrhea, progressive neurologic impairment and less frequently coronary heart disease, early onset osteoporosis and abnormalities in the optic disk and retina. An early diagnosis and treatment with quenodeoxycholic acid may prevent further complications, mainly neurological manifestations. This review summarizes cholesterol metabolism related to bile acid synthesis, physiopathology, biochemistry and treatment of cerebrotendinous xanthomatosis.