Estrategia para el diagnóstico de las dislipidemias. Recomendación 2018 / Strategy for the diagnosis of dyslipidaemias

Las dislipidemias son alteraciones del metabolismo lipídico que cursan con concentraciones de lípidos alteradas, tanto por exceso como por defecto. Estas alteraciones están fuertemente asociadas con el proceso aterosclerótico, y se ha demostrado que el control de dichas alteraciones consigue disminuir la incidencia de episodios de origen isquémico. Diagnosticar las dislipidemias desde un punto de vista etiológico es muy importante, ya que el riesgo cardiovascular al que predispone cada una de ellas es diferente, dependiendo del tipo de lipoproteína que esté alterada y de su concentración. Por ello es de gran utilidad disponer de algoritmos diagnósticos sencillos que incluyan magnitudes del metabolismo lipídico disponibles en la mayoría de los laboratorios clínicos, con el fin de realizar el diagnóstico inicial del tipo de dislipidemia, en caso de poseer las herramientas diagnósticas adecuadas identificarla y, en caso contrario, disponer de la información apropiada para recomendar la ampliación del estudio en otro centro que disponga de los recursos necesarios para establecer el diagnóstico

Dyslipidaemias are alterations in lipid metabolism that involve an excess, as well as a deficit, in lipid concentrations. These alterations are strongly associated with atherosclerosis, and it has been shown that its control reduces the incidence of episodes of ischaemic origin. Diagnosing dyslipidaemias from an aetiological point of view is very important, since the cardiovascular risk to which each one predisposes is different, and depends on the type of lipoprotein that is altered and its concentration. For this reason, it is very useful to have simple diagnostic algorithms that include the measurements of lipid metabolism that are available in most clinical laboratories in order to make the initial diagnosis of the type of dyslipidaemia. In the case of having the right diagnostic tools, identify it; and if not, to have the appropriate information to recommend the extension of the study in another centre with resources to establish the diagnosis

Recomendaciones para la estandarización de la medida de lípidos y lipoproteínas. Recomendación (2018) / Recommendations for the standardisation of lipids and lipoproteins measurements. Recommendation (2018)

Este documento describe recomendaciones para la estandarización de la medida de las magnitudes lipídicas, puesto que resultan críticas para la toma de decisiones clínicas. Deben emplearse métodos recomendados validados frente a un método de referencia o definitivo, y materiales de control que cumplan con la Directiva Europea sobre Diagnóstico in vitro; deben cumplir también los objetivos recomendados por el National Cholesterol Education Program (NCEP) y la Sociedad Española de Medicina del Laboratorio (SEQCML). La determinación de colesterol de HDL por métodos homogéneos en equipos automatizados se considera aceptable para la práctica rutinaria, y la fórmula de Friedewald utilizable para estimar la concentración de colesterol de LDL siempre que las concentraciones de triglicéridos sean iguales o inferiores a 200mg/dL (2,3mmol/L); en otro caso, se recomienda utilizar la concentración de colesterol-no-HDL. La cuantificación rutinaria de apolipoproteínas A1 y B, y lipoproteína (a), puede efectuarse por métodos de inmunonefelometría e inmunoturbidimetría, con calibradores trazables a materiales de referencia

Some recommendations are presented for standardising the measurement of lipids and lipoproteins, as they are critical for clinical decisions making. Recommended methods validated against a reference or definitive method should be employed, as well as the use of control materials that comply with European Directives on in vitro diagnostics. Additionally, the chosen methods must comply with the objectives set forth by the National Cholesterol Education Program (NCEP) and by the Spanish Society of Laboratory Medicine (SEQCML). Determination of HDL cholesterol using automatic homogenous methods is considered acceptable for normal clinical practice, and the Friedewald Formula is considered to be usable to estimate LDL cholesterol concentration when triglyceride concentrations are below 200mg/dL (2.3mmol/L). If this should not be the case, the use of non-HDL cholesterol is recommended. Routine quantification of apolipoproteins A1 and B, and lipoprotein (a) can be measured using immunonephelometric or immunoturbidimetric methods, with calibrators that are traceable to reference materials

A new metabolic disorder in human cationic amino acid transporter-2 that mimics arginase 1 deficiency in newborn screening.

PURPOSE: We report a patient with a human cationic amino acid transporter 2 (CAT-2) defect discovered due to a suspected arginase 1 deficiency observed in newborn screening (NBS). METHODS: A NBS sample was analyzed using tandem mass spectrometry. Screen results were confirmed by plasma and urine amino acid quantification. Molecular diagnosis was done using clinical exome sequencing. Dimethylated arginines were determined by HPLC and nitrate/nitrite levels by a colorimetric assay. The metabolomic profile was analyzed using 1D nuclear magnetic resonance spectroscopy. RESULTS: A Spanish boy of nonconsanguineous parents had high arginine levels in a NBS blood sample. Plasma and urinary cationic amino acids were high. Arginase enzyme activity in erythrocytes was normal and no pathogenic mutations were identified in the ARG1 gene. Massive parallel sequencing detected two loss-of-function mutations in the SLC7A2 gene. Currently, the child receives a protein-controlled diet of 1.2 g/kg/day with protein-and amino-acid free infant formula, 30 g/day, and is asymptomatic. CONCLUSION: We identified a novel defect in human CAT-2 due to biallelic pathogenic variants in the SLC7A2 gene. The characteristic biochemical profile includes high plasma and urine arginine, ornithine, and lysine levels. NBS centers should know of this disorder since it can be detected in arginase 1 deficiency screening.

Infantile sialidosis: natural history in a preterm infant with two new pathogenic mutations and new ocular findings.

Sialidosis is a rare lysosomal storage disease caused by an α-N-acetyl neuraminidase-1 deficiency due to mutations of the NEU1 gene (6p21). Disease severity varies among patients and is linked to the level of residual neuraminidase activity in vivo. At least 40 disease-causing mutations in the NEU1 gene have been reported. Sialidosis occurs in two main clinical variants: type I, the milder form of the disease, and type II, which is subdivided into congenital, infantile, and juvenile forms. We report the clinical, biochemical, and molecular characterization of a patient with infantile sialidosis type II. The abnormal urinary oligosaccharide profile is described for the first time. The genetic characterization of the patient showed two previously unreported missense mutations in the NEU1 gene: p.R78C (c.232C>T) and p.R290Q (c.869G>A).

Implications of the Mediterranean diet and physical exercise on the lipid profile of metabolically healthy obese women as measured by nuclear magnetic resonance spectroscopy (1H NMR).

OBJECTIVE: There is a lack of consensus when it comes to establishing the biochemical parameters that define metabolically healthy obese (MHO) subjects. Indeed, most studies do not include subjects' lipid profiles. Our objective was to characterize lipoprotein size, particle and subclass concentration using 1H NMR in MHO women after two years of weight loss with a hypocaloric Mediterranean diet and physical exercise. METHODS: 115 non-diabetic women (aged 35-55 years) with a body mass index (BMI) of 30-40 kg/m2 and ≤1 of the following criteria: blood pressure ≥135/85 mmHg, fasting plasma glucose ≥100 mg/dL, HDL cholesterol ≤50 mg/dL and triglycerides ≥150 mg/dL were included. After two years of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5%-<10% and ≥10%. Lipoprotein size, particle and subclass concentrations were measured using 1H NMR. RESULTS: The final population, after dropouts, were 67 women (age: 44.5 ±â€¯3.7 years, BMI: 36.3 ±â€¯4.7 kg/m2), of whom 23 (38.3%) lost <5%, and 22 (36.7%), lost ≥5% to <10% and ≥10% of baseline body weight, respectively. The lipid profile showed no significant changes after intervention, especially in small LDL particles or in production of HDL. The diameter of LDL and HDL particles did not change after two years of a Mediterranean diet and physical exercise. CONCLUSION: These results indicate that intensive lifestyle modification does not produce significant changes in the lipid profile of MHO women. Levels of more atherogenic or atheroprotective particles did not change after two years, despite the intervention.

Characterization of lipid profile by nuclear magnetic resonance spectroscopy (1H NMR) of metabolically healthy obese women after weight loss with Mediterranean diet and physical exercise.

Obesity is associated with an atherogenic lipid profile. No data exists on lipoprotein particle profiles in metabolically healthy obese (MHO) individuals. Our aim is to characterize lipoprotein size, particle, and subclass concentrations in MHO women after 3 months of weight loss through dietary restriction and physical exercise.A total of 115 nondiabetic women (aged 35-55 years) with a body mass index (BMI) of 30 to 40 kg/m and ≤1 of the following criteria: blood pressure ≤135/85 mm Hg, fasting plasma glucose ≤100 mg/dL, HDL-cholesterol ≤50 mg/dL, and triglycerides ≤150 mg/dL were included. After 3 months of intensive lifestyle modification (Mediterranean diet and physical exercise), they were classified according to their weight loss: <5%, ≥5% to <10%, and ≥10%. Lipoprotein size, particle, and subclass concentrations were measured using H NMR.The final sample, after dropouts, comprised 104 women (age: 44.4 ±â€Š3.7 years, BMI: 36.3 ±â€Š4.7 kg/m), of whom 47 (45.2%), 27 (26%), and 30 (28.8%) lost <5%, ≥5% to <10%, and ≥10% of baseline body weight, respectively. All participants experienced significant weight loss and decreases in BMI. The lipid profiles showed an increase in small, medium, and large very low density lipoprotein (VLDL) particles in all groups of study with the exception of small VLDL particles in women with ≥10% of weight loss, in which it decreased. The number of VLDL particles decreased in women who had ≥10% weight loss. On the other hand, we detected a decrease in all low density lipoprotein (cLDL) and high density lipoprotein (cHDL) concentrations.These results indicate that intensive lifestyle modification alters lipid profiles. In particular, it decreases small LDL and HDL particle numbers and does not increase medium or large HDL particles numbers.