Xantomas eruptivos: manifestación cutánea de desórdenes de las lipoproteínas / Eruptive xanthomas: skin manifestation of the lipoprotein disorders

Los xantomas constituyen tumores cutáneos, y se presentan por depósitos de lipoproteínas en los macrófagos tisulares. Clínicamente se manifiestan como lesiones papulosas o nodulares de color amarillento, estando relacionada su distribución con las diferentes formas clínicas de presentación. Aunque no se observan con frecuencia, su presencia puede alertar sobre la existencia de alteraciones en los niveles lipídicos en sangre, y es por lo que se presentó este caso, donde la presencia de los xantomas fue indicador de un incremento de los niveles de colesterol y triglicéridos, lo que pudo constituir un importante factor de riesgo para que la paciente presentara alteraciones en otros sistemas...

Xanthomas are skin tumors, and they present as a cause of lipoprotein deposits in tissue macrophages. Clinically they take the form of yellow papular or nodular lesions, being related its distribution with their different forms of presentation. Though they are not very frequent, their presence can alert about the existence of alterations in the lipid levels in blood. That is why we presented this case, where the presence of xanthomas was an indicator of the cholesterol and triglycerides level increase, what probably was an important risk fact for the patient to present alterations in other systems...

Cincuenta años de estudio de las hiperlipidemias primarias: el caso de la hiperlipidemia familiar combinada / Fifty years studying hiperlipidemias: the case of familial combined hyperlipidemia

La hiperlipidemia familiar combinada (HLFC) es la dislipidemia primarias más frecuente en México. Se manifiesta por hipercolesterolemia, hipertrigliceridemia o la combinación de estos defectos. Pese a su frecuencia, pocas veces es diagnosticada con certidumbre. Se requiere del estudio de al menos tres familiares directos para corroborar el diagnóstico. En esta revisión se describen los avances ocurridos en los últimos años sobre la fisiopatología y diagnóstico de la hiperlipidemia familiar combinada. Estudios prospectivos han confirmado la aterogenicidad de la enfermedad. Por ser una enfermedad oligogénica es factible identificar los genes involucrados con los recursos ahora existentes. Gracias al uso de nuevas tecnologías, se han identificado regiones cromosómicas que determinan la concentración de la apolipoproteína B y se demostró que diferencias en la actividad o concentración de varios factores nucleares (USF1, TCF7L2, HNF4alfa) juegan un papel importante en la fisiopatología de la HLFC. Los factores nucleares antes mencionados regulan la expresión de múltiples genes que participan en el metabolismo de lípidos y carbohidratos.

Familial combined hyperlipidemia (FCHL) is the most frequent primary dyslipidemia. Its manifestations include hypercholesterolemia, hypertriglyceridemia or the combination of both abnormalities. In spite of its high frequency, the proper diagnosis is rarely done. For this purpose, the measurement of a lipid profile is required in at least three first-degree relatives. A critical review of the current literature in this field is presented in this paper. Prospective studies have confirmed the atherogenicity of the disease. It is possible to identify the FCHL causal genes with the current methodology because it is an oligogenic disease. Based on the use of new technologies, several loci that regulate apolipoprotein B concentrations have been identified. In addition it was demostrated that variations of the activity or the expression of various nuclear factors (USF1, TCF7L2, HNF4alfa) have a major role in the pathophysiology of FCHL. These nuclear factors regulate the expression of multiple genes involved in the metabolism of lipids or carbohydrates.

Taq1B polymorphism of cholesteryl ester transfer protein (CETP) gene in primary combined hyperlipidaemia.

Background & objectives: Cholesteryl ester transfer protein (CETP) gene polymorphism is known to be associated with changes in lipid profiles. Primary hyperlipidaemia is considered to be a major risk factor for pancreatitis, atherosclerosis and coronary heart disease. We investigated the association of one common polymorphism in the CETP gene (Taq1B) with plasma lipid levels and CETP activity in Iranian subjects with and without primary combined hyperlipidaemia. Methods: The study included 102 patients with primary combined hyperlipidaemia and 214 health individuals. Polymerase chain reaction and restriction fragment length polymorphisms were used for genotype detection. To determine the relationship between Taq1B polymorphism and lipid levels, lipids and CETP activity were measured in primary combined hyperlipidaemic and normolipidaemic subjects, with and without Taq1B polymorphism. Results: Plasma CETP activity was significantly (P<0.001) higher in primary combined hyperlipidaemic individuals than in controls. Plasma HDL-C was higher in both groups, in the B2B2 genotype than in the B1B1 and B1B2 genotypes, whereas the serum TG concentrations and CETP activity were lower in B2B2 genotype compared with other genotypes (B1B1 and B1B2). The genotype and allelic frequencies for this polymorphism differed significantly between hyperlipidaemic and nonmolipidaemic individuals (P<0.05). In both groups, CETP Taq 1B polymorphism (presence of B2 allele) correlated significantly with HDL-cholesterol (HDL-C) (r=0.201 and r=0.452 in control and patient groups respectively) and CETP activity (r= -0.123 for controls and r= -0.192 for patients). Interpretation & conclusions: The results showed that Taq 1B polymorphism of CETP gene was associated with changes in lipids profile and plasma CETP activity in the selected population and might have a role in contributing to genetic risk of developing coronary artery disease.

Identification of loci conferring risk for premature CAD and heterozygous familial hyperlipidemia in the LDLR, APOB and PCSK9 genes

Heterogeneous familial hypercholesterolemia [HFH] partly underlies polymorphic changes in the low-density lipoprotein receptor [LDLR], apolipoprotein B [APOB] and protein convertase subtili-sin/kexin type 9 [PCS/C9], exhibiting intra-ethnical variations in its clinical features. Methods: We employed the Affymetrix whole genome scan 250 styl array to characterize possible geno-mic linkage to heterozygous familial hypercholesterolemia [HFH] and sequencing techniques to identify related mutations in the above three genes in a Saudi family of 11 individuals harbouring clinical features of FH. The propositus had early onset of coronary artery disease [CAD] and very significantly elevated cholesterol [Chol] level of 10.1 mmol/L and LDL-cholesterol [LDL-C] of 7.9 mmol/L as well as low HDL-C level of 0.51 mmol/L, while 4 siblings were affected with HFH.. Whole genome scan for the autosomal dominant model showed high homology for the affected individuals in several regions including chromosomes [chr] 1 and 2 which harbour PCSK9 and APOB, respectively. Subsequent sequencing of the coding regions of these two and LDLR identified 11 single nucleotide polymorphisms [SNPs] in the LDLR, 8 in the APOB and 6 in the PCSK9 genes. The propositus uniquely carried the homozygous mutant genotypes [haplotype] for all 11 LDLR SNPs, in direct contrast to the only normolipidemic sibling and a control who carried the homozygous wild type genotypes at these loci. Another set of 7 SNPs in the APOB also isolated with FH. Interestingly, all family members were heterozygous for all except the rs2228671 C > T of this gene, for which the mother shared the C/C genotype with the propositus, two other affected off-springs and a control, all of whom exhibited low HDL-C levels. A confirmation experiment involving 70 individuals harbouring low HDL-C revealed 74.3% of them as C/C carriers. Our study identified a haplotype in the LDLR as a marker for early onset of CAD, and rs2228671 C > T in the LDLR in association with a reduction in HDL-C concentrations in FH. The results also substantiate the notion of genetic heterogeneity in HFH, underlining the essence of recognizing ethnic-specific gene variability as a potential basis for appropriate management of FH

Familial combined hyperlipidemia with tuberous and tendinous xanthomas: A case report

Familial combined hyperlipidemia, otherwise known as type IIb hyperlipoproteinemia or multiple lipoprotein-type hyperlipidemia is an inherited disorder of high serum cholesterol or high blood triglycerides. This disease is genetic and inherited, although the specific defective genes have not been identified. The person's cholesterol or triglyceride become elevated during the teenage years and continue to be high throughout life. The types of elevated lipoproteins may vary between affected family members. Its clinical manifestations include lipid disposition on the skin or tendons called "xanthomas" as well as on the arteries. People with this condition have an increased risk of cardiovascular disease so that it is essential to recognize early this type of disorder. We report a case of a 37 year-old male who presented with a bilateral yellowish to reddish nodules on the elbows, knees, ankles, malleoili, ventral aspect of both hands, fingers, feet and toes, metacarpophalangeal & proximal interphalangeal joints, back and buttocks of six years duration with an elevated levels.

Familial combined hyperlipidemia in a North Indian kindred.

Familial combined hyperlipidemia is the most common genetic hyperlipidemia and is responsible for premature coronary artery disease. It is genetically heterogenous and no single diagnostic marker exists. The authors report an affected North Indian kindred spanning three successive generations with a possible autosomal dominant pattern of inheritance and all of them had combined dyslipidemia [elevated total cholesterol, predominantly the low density lipoprotein (LDL) fraction and elevated triglycerides]. The proband, a 4-month-old male baby, was incidentally discovered to have a lipaemic serum and so further evaluated. Both the index case and his maternal grandmother, a non-obese diabetic (type 2) with hypertension, had an atherogenic lipoprotein phenotype. Lipaemia retinalis was documented in this baby but xanthomas and coronary artery disease were not noted in the kindred. The present case report highlights the failure of dietary therapy in the proband and explores new options.

A case of acute hyperlipidemic pancreatitis in a patient suspected of familial combined hyperlipidemia / 대한내과학회지

It is well recognized that there is an association between hyperlipidemia and pancreatitis. However, it is not so easy to define clearly whether lipid abnormalities are the cause or the result of pancreatitis. Generally, a serum level of more than 1,000 mg/dL of triglyceride is an identifiable risk factor of hyperlipidemic pancreatitis in patients with type I, IV, or V hyperlipidemia classified by Fredrick's criteria. The clinical course as well as the management of hyperlipidemic pancreatitis is not different from that of pancreatitis of other causes. A thorough family history of lipid abnormalities should be obtained and an attempt to identify secondary causes should be made. The mainstay of treatment includes dietary restriction of fat and lipid-lowering medications. In Korea, there have been reported several cases of hyperlipidemic pancreatitis but familial history of hyperlipidemia has never been identified. We experienced a case of acute type IV hyperlipidemic pancreatitis in a patient suspected of familial combined hyperlipidemia. So, we report this case with the review of related literature.

Normal lipid metabolism, familial hyperlipidaemia, lipid intervention and their benefits.

Some recent developments in lipoprotein metabolism, familial hyperlipidaemias and lipid lowering therapies with reference to coronary artery disease (CAD) are reviewed. LDL-cholesterol (LDL-C) level and particle subclass are important determinants of the extent of cholesterol delivery to the peripheral tissues and thereby of atherogenesis and CAD. LDL modifications (eg, oxidation, adduct formation, desialylation, glycation, etc) enhance the above process. HDL particles bring cholesterol from peripheral tissues to liver (reverse cholesterol transport, RCT). ApoA1, LCAT enzyme, ABCA1 and cholesterol ester transfer protein are involved in RCT. Paraoxonase of HDL prevents oxidation of other lipoproteins and probably hinders atherogenesis. Lp(a) particles are like LDL except the presence of apo(a) that inhibits fibrinolysis and are epidemiologicaly linked to the development of CAD. Indians have high Lp(a), in comparison to whites. Familial hyperlipidaemias are due to altered metabolism of lipoproteins affecting plasma lipid profile. Majority of such patients are prone to atherosclerosis and CAD. LDL-C is the primary target of lipid lowering therapy. Statins inhibit HMG-CoA reductase and are mainly used alone or with other drugs for lowering blood lipids. 'National Cholesterol Education Program' now recommends a stringent LDL-C control ( < 100 mg/dl) for CAD and CAD risk equivalents. Therapeutic lifestyle changes and drug therapy are the main modalities to reduce blood lipids, aiming at total reduction of short-and long-term coronary risk for all (primary prevention), and of coronary mortality and morbidity in patients with CAD (secondary prevention).

Dyslipidemia of atheromatous patients

Study on 210 patients including 120 atheromatous patients, 90 non-atheromatous patients at Transfusion Blood Center in HCMC. Research results showed that: the lipid-lipoprotein disorders had colleration to atheromatous. It was statistical. Hypercholesterolemia 62.6%, hypertriglycerid 51.6%, hypo HDL-C 48.3%, hyper LDL-C 45.8%. The lipid-lipoprotein disorders and atheroscelrosis on the over forty year old patients were higher than the young patients but there was no difference between male and female

Dislipidemia en el escolar y adolescente / Dislipidemia in school children and adolescents

Las enfermedades cardiovasculares constituyen la primera causa de morbimortalidad en la población adulta de la mayoría de los países desarrollados y también en Chile. Entre éstas, la primera causa individual corresponde a la enfermedad coronaria, cuya relación con la concentración de lípidos plasmáticos, especialmente colesterol de lipoproteína de baja densidad (LDL), ha sido claramente establecida

Xantomas eruptivos / Eruptives xanthomas

Se presentan dos pacientes con xantomas eruptivos. Se describe la clínica e histopatología de esta enfermedad y se enumeran los diagnósticos diferenciales. Se destaca la importancia de dicha patología en el descubrimiento de una hiperlipidemia muchas veces ignorada, que puede poner en peligro la vida del paciente

One Family of Familial Combined hyperlipidemia Associated with Various Metabolic Abnormalities / 대한내분비학회지

Familial combined hyperlipidemia is one af the manogenic disorders frequently found in humans and is seen in 0.5~2% of the general populatian, accounting for at least 10% of persons with pemature atlmmcletusis. The distinguishing feature of familial combined hyperlipidemia, in camparison with other single-gene abnarmalities of lipoprotein metabolism, is that not all affected members have the same plasma lipid phenotype; some individuals have an elevation of cholesterol concentration alane(type IIa lipoprotein pattern), while some athers have an elevation of triglyceride concentration alone(type IV pattem), and still others have elevations of both values(type IIb pattem). In any one persan, the lipid phenotype can change as a result of dietary or drug treatment. Familial combined hyperlipidemia should be suspected in those subjects with moderate hypertriglyceridemia and/or moderate hypercholestaolemia (lipoprotein types IIa, Ilb, IV), especially when premature coronary heart disease is evident in the family histary. Low plasma HDL-cholesterol, obesity, insulin resistance and hyperuricemia are often . Family members affected by familial combined hyperlipidemia should be identified and be treated, since tbe condition is associated with premature caronary heart diasease. We have found one family of familial combined hyperlipidemia with one member(case 1) associated with insulin resistance, hyperuricemia and gout, and another member(case 2) associated with diabetes mellitus and infertiTity.

Gemfibrozil in familial and type V hyperlipidaemias. Report of 3 cases.

Gemfibrozil, a lipid lowering agent, was administered to two patients with familial hyperlipidaemia and one patient with insulin dependent diabetes mellitus. It was partially effective in familial hyperlipidaemia. It dramatically reduced triglyceride and cholesterol levels in the patient with Type V hyperlipidaemia and insulin dependent diabetes mellitus. Patients with familial and Type V hyperlipidaemias should be given a trial of gemfibrozil therapy.

Hiperlipidemia familiar combinada.Estudio de una familia. / Combined familial hyperlipidemia. Study of a family

Se estudiaron 15 miembros de una familia con hiperlipidemia familiar combinada, en los que observamos las caracteristicas clinicas principales de este trastorno. El analisis del pedigree y los valores de colesterol y trigilceridos permiten postular un mecanismo de transmision autosomico dominante. El 50 de los individuos de la generacion de los probandos demonstraron valores de lipidos diagnosticos de hiperlipidemia. En base a los valores absolutos de colesterol y trigiceridos, asi como a la electroforesis de lipoproteinas en suero se diagnosticaron los patrones de Fredrickson IIa, IIb, y IV, con una frecuencia similar, de aproximadamente 33% para cada uno de los fenotipos entre los individuos afectados.Los valores medios de colesterol y trigliceridos ajustados para edad y sexo entre los miembros hiperlipidemicos fueron de 308.9 mg/dl (> P95) y 252.1 mg/dl (> P90) respectivamente, mientras que en los casos no afectados correspondieron a 212.1 mg/dl (< P50) para colesterol y 124.9 mg/dl (< P50) para trigliceridos. Se observo claramente en esta familia la existencia de cardiopatia ateroesclerosa prematura, incluyendo 3 casos de muerte a edad temprana por infarto miocardico