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Familial hypercholesterolemia is a genetically determined disease characterized by elevated plasma total and LDL cholesterol levels from the very first years of life, leading to early atherosclerosis. Nutritional intervention is the first-line treatment, complemented with nutraceuticals and drug therapy when necessary. Nutraceuticals with a lipid-lowering effect have been extensively studied in the past few decades, and have been recently included in international guidelines as a complement to nutritional and pharmacological treatment in subjects with dyslipidemia. In this review, we explore current nutritional interventions for dyslipidemia in childhood, with a specific focus on the main nutraceuticals studied for treating severe dyslipidemia in pediatric patients. Additionally, we briefly describe their primary mechanisms of action and highlight the advantages and risks associated with the use of lipid-lowering nutraceuticals in childhood.
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The atherosclerotic process begins in childhood and progresses throughout adult age. Hypercholesterolemia, especially familial hypercholesterolemia (FH) and metabolic dysfunctions linked to weight excess and obesity, are the main atherosclerosis risk factors in pediatric patients and can be detected and treated starting from childhood. Nutritional intervention and a healthy-heart lifestyle are cornerstones and first-line treatments, with which, if necessary, drug therapy should be associated. For several years, functional foods enriched with plant sterols and stanols have been studied in the treatment of hypercholesterolemia, mainly as nutritional complements that can reduce LDL cholesterol; however, there is a lack of randomized controlled trials defining their long-term efficacy and safety, especially in pediatric age. This review aims to evaluate what the main published studies on sterols and stanols in pediatric subjects with dyslipidemia have taught us, providing an updated picture of the possible use of these dietary supplements in children and adolescents with dyslipidemia and increased cardiovascular risk. Nowadays, we can state that plant sterols and stanols should be considered as a valuable therapy in pediatric patients with hypercholesterolemia, bearing in mind that nutritional and lifestyle counseling and, when necessary, pharmacologic therapy, are the cornerstones of the treatment in developmental age.
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Detection and treatment of patients with familial hypercholesterolemia (FH) starting from childhood is fundamental to reduce morbidity and mortality. The activity of National realities such as the LIPIGEN (LIpid transPort disorders Italian GEnetic Network) Paediatric Group, founded in 2018, is a milestone in this context. The aim of this exploratory survey, conducted in October 2021 among Italian lipid clinics included in the LIPIGEN Paediatric Group, was to investigate the current clinical approach in the management and treatment of paediatric patients with suspected FH. A digital questionnaire composed of 20 questions investigating nutritional treatment and nutraceutical and pharmacological therapy for children and adolescents with FH was proposed to the principal investigators of 30 LIPIGEN centres. Twenty-four centres responded to the section referring to children aged < 10 years and 30 to that referring to adolescents. Overall, 66.7% of children and 73.3% of adolescents were given lipid-lowering nutritional treatment as the first intervention level for at least 3-4 months (29.2% and 23.3%) or 6-12 months (58.3% and 53.3%). Nutraceuticals were considered in 41.7% (regarding children) and 50.0% (regarding adolescents) of the centres as a supplementary approach to diet. Lipid-lowering drug therapy initiation was mainly recommended (91.7% and 80.0%). In 83.3% of children and 96.7% of adolescents, statins were the most frequently prescribed drug. We highlighted several differences in the treatment of paediatric patients with suspected FH among Italian centres; however, the overall approach is in line with the European Atherosclerosis Society (EAS) recommendations for FH children and adolescents. We consider this survey as a starting point to reinforce collaboration between LIPIGEN centres and to elaborate in the near future a consensus document on the management of paediatric patients with suspected FH so as to improve and uniform detection, management, and treatment of these patients in our country.
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Anticolesterolemiantes , Dieta , Suplementos Nutricionais , Hiperlipoproteinemia Tipo II , Humanos , Masculino , Feminino , Criança , Adolescente , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/terapia , Anticolesterolemiantes/uso terapêuticoRESUMO
BACKGROUND AND AIMS: We aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age. METHODS: From the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation. RESULTS: The lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives. CONCLUSIONS: In children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age.
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Doença da Artéria Coronariana , Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Criança , Adolescente , Fatores de Risco , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , HeterozigotoRESUMO
Familial hypercholesterolaemia (FH) is a frequent genetic disorder characterised by high plasma levels of total and LDL-cholesterol and premature atherosclerosis. If left untreated, affected subjects have a high risk of cardiovascular disease, as they are exposed to very high levels of LDL-cholesterol from birth. Healthy dietary habits and lifestyle are the first treatment option and, if started from childhood, represent a milestone in the prevention of atherosclerotic disease, both as a starting point and in combination with drug therapy. In this work, based on the main consensus documents available so far, we have evaluated the most up-to-date indications of the dietetic-nutritional intervention for the treatment of FH, delving into the peculiar aspects of the diet of the child/adolescent affected by FH. After an analysis of the macro- and micronutrients and the most common dietary patterns currently recommended, we highlighted some practical aspects, some frequent errors and some risks we could fall into when dealing with paediatric nutritional treatment. In conclusion, the dietary intervention for the child/adolescent with FH is a complex task, that should be individualised and tailored taking into account, first of all, the nutritional adequacy for growth and development, but also the multiple aspects linked to the child/adolescent's age, tastes and preferences, the family they belong to, the socio-economic context and the Country they live in.
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Aterosclerose , Hiperlipoproteinemia Tipo II , Criança , Humanos , Adolescente , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/genética , LDL-Colesterol/uso terapêutico , Dieta , Estilo de VidaRESUMO
[This corrects the article DOI: 10.3389/fgene.2022.912510.].
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Hypertriglyceridemia is a lipid disorder with a varying prevalence; it is very common if we consider triglyceride plasma values slightly above the threshold, whereas it is extremely rare if only severely elevated triglyceride levels are considered. In most cases, severe forms of hypertriglyceridemia are caused by genetic mutations in the genes that regulate triglyceride metabolism, thus leading to extreme triglyceride plasma values and acute pancreatitis risk. Secondary forms of hypertriglyceridemia are usually less severe and are mainly associated with weight excess, but they can also be linked to liver, kidney, endocrinologic, or autoimmune diseases or to some class of drugs. Nutritional intervention is the milestone treatment for patients with hypertriglyceridemia and it has to be modulated on the underlying cause and on triglyceride plasma levels. In pediatric patients, nutritional intervention must be tailored according to specific age-related energy, growth and neurodevelopment requests. Nutritional intervention is extremely strict in case of severe hypertriglyceridemia, whereas it is similar to good healthy nutritional habits counselling for mild forms, mainly related to wrong habits and lifestyles, and to secondary causes. The aim of this narrative review is to define different nutritional intervention for various forms of hypertriglyceridemia in children and adolescents.
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Hipertrigliceridemia , Pancreatite , Adolescente , Humanos , Criança , Doença Aguda , Pancreatite/complicações , Dieta , TriglicerídeosRESUMO
BACKGROUND: It is now well established that atherosclerosis begins in childhood and evolves through adolescence and young adulthood, ultimately resulting in myocardial infarction and stroke in adults. MAIN TEST: Childhood is a critical phase during which atherosclerosis may begin to develop; in the presence of familial hypercholesterolemia, lifelong elevation of Low Density Lipoprotein cholesterol levels greatly accelerates atherosclerosis. These concepts, which have been largely developed from epidemiologic evidence, have not always been simple to implement in the paediatric clinical practice. The purpose of this article is to briefly review but also to highlight the rationale, the motivation and the methods in the process of identifying children and adolescents with familial hypercholesterolemia, an often hidden but very important genetic disease.
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Aterosclerose , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Acidente Vascular Cerebral , Adolescente , Adulto , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Criança , LDL-Colesterol , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Adulto JovemRESUMO
Background and aims: Familial Hypercholesterolaemia (FH) is characterised by a genetic alteration in the transport and metabolism of cholesterol that leads to elevated levels of total cholesterol (CT) and low-density lipoprotein cholesterol (LDL-C) and early onset of atherosclerosis. According to the current guidelines, diet and promotion of healthy habits are first-line treatments. Little is known about the effectiveness of cholesterol-lowering diet and healthy lifestyle habits on plasma cholesterol and lipid profile in children and adolescents with FH. The aim of the study is to investigate the effect of the nutritional counseling on plasma lipid profile in FH children at the first step of treatment. Methods: 115 FH children (2−17 years) were included in the study; dietary habits were evaluated through a Food Frequency Questionnaire (FFQ) and blood samples for lipid profile were collected at the enrollment (T0) and six months later (T1). Results: the lipid profile at T0 and T1, expressed as mean ± standard deviation in mg/dL, was, respectively: total cholesterol 285.9 ± 51.1 and 276.6 ± 46.8 (paired test difference p value < 0.01), LDL-cholesterol 214.9 ± 47.7 and 206.4 ± 46.6 (p value < 0.01), HDL-cholesterol 52.9 ± 13 and 54.4 ± 11.5 (p value 0.07), triglycerides 87 ± 46.7 and 82.2 ± 38.4 (p value 0.4), non-HDL cholesterol 233 ± 51.4 and 222.2 ± 47.4 (p < 0.01). In the dietary habits (weekly portions) we observed an improvement (p ≤ 001) for fruit and vegetables, fish, pulses, whole foods, and a reduction (p < 0.01) for meat, sausages, cheese, junk foods consumption. Conclusions: In FH children we have highlighted an improvement of the plasma lipid profile and in healthy dietary habits after nutritional counseling.
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Hiperlipoproteinemia Tipo II , Adolescente , Criança , Pré-Escolar , Colesterol/sangue , HDL-Colesterol , LDL-Colesterol , Dieta Saudável , Humanos , Hiperlipoproteinemia Tipo II/dietoterapia , Triglicerídeos/sangueRESUMO
Pathology registers can be a useful tool to overcome obstacles in the identification and management of familial hypercholesterolemia since childhood. In 2018, the LIPIGEN pediatric group was constituted within the Italian LIPIGEN study to focus on FH subjects under 18 years. This work aimed at discussing its recent progress and early outcomes. Demographic, biochemical, and genetic baseline characteristics were collected, with an in-depth analysis of the genetic defects. The analysis was carried out on 1,602 children and adolescents (mean age at baseline 9.9 ± 4.0 years), and almost the whole cohort underwent the genetic test (93.3%). Overall, the untreated mean value of LDL-C was 220.0 ± 97.2 mg/dl, with an increasing gradient from subjects with a negative (N = 317; mean untreated LDL-C = 159.9 ± 47.7 mg/dl), inconclusive (N = 125; mean untreated LDL-C = 166.4 ± 56.5 mg/dl), or positive (N = 1,053; mean untreated LDL-C = 246.5 ± 102.1 mg/dl) genetic diagnosis of FH. In the latter group, the LDL-C values presented a great variability based on the number and the biological impact of involved causative variants. The LIPIGEN pediatric group represents one of the largest cohorts of children with FH, allowing the deepening of the characterization of their baseline and genetic features, providing the basis for further longitudinal investigations for complete details.
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BACKGROUND AND AIMS: Little is known about the role of Lp(a) in the assessment of cardiovascular risk in the paediatric population. Trying to clarify the clinical relevance of Lp(a) in risk stratification, the aim of the study is to evaluate the association between Lp(a) plasma levels in children with familial hypercholesterolaemia (FH) and positive family history for premature cardiovascular disease (pCVD) in first- and second-degree relatives. METHODS: 653 Caucasian children and adolescents (334 females and 319 males), aged 2-17 years, with diagnosis of FH from a paediatric cohort included in the LIPIGEN Network, were selected. We compared family history of pCVD, lipid and genetic profile in two groups based on Lp(a) levels below or above 30 mg/dL. To determine the independent predictors of pCVD, a multivariate logistic regression was used, with all clinical characteristics and blood measurements as predictors. RESULTS: Subjects with Lp(a) > 30 mg/dl more frequently reported positive family history of pCVD compared to subjects with Lp(a)≤30 mg/dl (69.90% vs 36.66%, p < 0.0001), while did not show differences in terms of median [interquartile range] LDL-cholesterol level (153.00 [88.00 vs 164.50 [90.25] mg/dL, p = 0.3105). In the regression analysis, Lp(a) > 30 mg/dl was an independent predictor of family history of pCVD. Comparing subjects with or without family history of pCVD, we reported significant differences for Lp(a) > 30 mg/dl (46.25% vs 17.65%, p < 0.0001), FH genetic mutation (50.48% vs 40.75%, p = 0,0157), as well as for LDL-cholesterol (p = 0.0013) and total cholesterol (p = 0.0101). CONCLUSIONS: Children/adolescents with FH and Lp(a) > 30 mg/dl where more likely to have a positive family history of pCVD. Lp(a) screening in children and adolescents with FH may enhance risk assessment and help identify those subjects, children and relatives, at increased pCVD risk.
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Doenças Cardiovasculares , Hiperlipoproteinemia Tipo II , Adolescente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Criança , LDL-Colesterol , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Lipoproteína(a)/genética , Masculino , Fatores de RiscoRESUMO
Coronary heart disease (CHD) is the main cause of death and morbidity in the world. Childhood is a critical period during which atherosclerosis may begin to develop; in the presence of familial hypercholesterolaemia (FH), the lifelong elevation of LDL cholesterol levels greatly accelerates atherosclerosis. Lowering LDL-C levels is associated with a well-documented reduction in cardiovascular disease risk. Current guidelines support the dietary and lifestyle approach as the primary strategy of intervention in children and adolescents with FH. Nutraceuticals (functional foods or dietary supplements of plant or microbial origin) are included in the EU guidelines as lifestyle interventions and may provide an additional contribution in reducing LDL levels when pharmacological therapy is not yet indicated. Meta-analyses of randomised clinical trials have demonstrated that the same nutraceuticals improve lipid profile, including lowering LDL-C, total cholesterol and triglyceride levels. In this narrative review, starting from current scientific evidence, we analyse the benefits and limitations of the nutraceuticals in children and adolescents with dyslipidaemia, and we try to evaluate their use and safety in clinical practice.
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Aterosclerose , Dislipidemias , Hiperlipoproteinemia Tipo II , Adolescente , Criança , Suplementos Nutricionais , Dislipidemias/terapia , Alimento Funcional , HumanosRESUMO
Coronary Heart Disease (CHD) is a major mortality and morbidity cause in adulthood worldwide. The atherosclerotic process starts even before birth, progresses through childhood and, if not stopped, eventually leads to CHD. Therefore, it is important to start prevention from the earliest stages of life. CHD prevention can be performed at different interventional stages: primordial prevention is aimed at preventing risk factors, primary prevention is aimed at early identification and treatment of risk factors, secondary prevention is aimed at reducing the risk of further events in those patients who have already experienced a CHD event. In this context, CHD risk stratification is of utmost importance, in order to tailor the preventive and therapeutic approach. Nutritional intervention is the milestone treatment in pediatric patients at increased CHD risk. According to the Developmental Origin of Health and Disease theory, the origins of lifestyle-related disease is formed in the so called "first thousand days" from conception, when an insult, either positive or negative, can cause life-lasting consequences. Nutrition is a positive epigenetic factor: an adequate nutritional intervention in a developmental critical period can change the outcome from childhood into adulthood.
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Doenças Cardiovasculares/prevenção & controle , Transtornos da Nutrição Infantil/dietoterapia , Desnutrição/dietoterapia , Terapia Nutricional , Adolescente , Desenvolvimento do Adolescente , Fatores Etários , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Criança , Desenvolvimento Infantil , Transtornos da Nutrição Infantil/diagnóstico , Transtornos da Nutrição Infantil/fisiopatologia , Fenômenos Fisiológicos da Nutrição Infantil , Pré-Escolar , Fatores de Risco de Doenças Cardíacas , Humanos , Lactente , Recém-Nascido , Desnutrição/diagnóstico , Desnutrição/fisiopatologia , Estado Nutricional , Prevenção Primária , Medição de Risco , Resultado do TratamentoRESUMO
Coronary heart disease (CHD) is the main cause of death and morbidity in the world. There is a strong evidence that the atherosclerotic process begins in childhood and that hypercholesterolaemia is a CHD major risk factor. Hypercholesterolaemia is a modifiable CHD risk factor and there is a tracking of hypercholesterolaemia from birth to adulthood. Familial hypercholesterolaemia (FH) is the most common primitive cause of hypercholesterolaemia, affecting 1:200-250 individuals. Early detection and treatment of hypercholesterolaemia in childhood can literally "save decades of life", as stated in the European Atherosclerosis Society Consensus. Multiple screening strategies have been proposed. In 2008, the American Academy of Pediatrics published the criteria for targeted screening, while some expert panels recommend universal screening particularly in the young, although cost effectiveness has not been fully analysed. Blood lipid profile evaluation [total cholesterol, Low-Density Lipoprotein Cholesterol (LDL-C), High-Density Lipoprotein Cholesterol (HDL-C) and triglycerides] is the first step. It has to be ideally performed between two and ten years of age. Hypercholesterolaemia has to be confirmed with a second sample and followed by the detection of family history for premature (before 55 years in men and 60 years in women) or subsequent cardio-vascular events and/or hypercholesterolaemia in 1st and 2nd degree relatives. The management of hypercholesterolaemia in childhood primarily involves healthy lifestyle and a prudent low-fat diet, emphasising the benefits of the Mediterranean diet. Statins are the cornerstone of the drug therapy approved in USA and in Europe for use in children. Ezetimibe or bile acid sequestrants may be required to attain LDL-C goal in some patients. Early identification of children with severe hypercholesterolaemia or with FH is important to prevent atherosclerosis at the earliest stage of development, when maximum benefit can still be obtained via lifestyle adaptations and therapy. The purpose of our review is to highlight the importance of prevention and treatment of hypercholesterolaemia starting from the earliest stages of life.
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BACKGROUND: Cardiovascular disease (CVD) is one of the main causes of mortality and morbidity in Italy. Hypercholesterolemia is a modifiable CVD risk factor. The detection and treatment of hypercholesterolemia can modify the natural history of CVD, making CVD risk for affected patients comparable to that of unaffected ones. In this scenario, the detection of families at high cardiovascular risk is the first step of CVD prevention. This multicenter, observational study is aimed at finding an effective and non-invasive screening strategy to detect families at high risk for CVD. METHODS: A survey investigating the knowledge of lipid and CVD issues was distributed to the parents of all infants born at the Neonatology Unit of Piacenza City Hospital and San Paolo Hospital in Milan over a 6 months period. Overall, 554 surveys have been collected. RESULTS: 26.8% newborns had parents who knew their own lipid profile, 40.2% had parents who knew the correct normal blood values of total cholesterol, 37.1% had parents who declared to have first or second degree relatives with lipid disorders, 33.7% had parents who declared to have first or second degree relatives with premature CVD CONCLUSION: Collecting a problem-tailored and accurate family history seems to be a good strategy to detect high risk families. Our data suggest that the percentage of adults who are unaware of their lipid profile, with a positive family history for CVD and/or lipid disorders is higher than expected. As a result, even the number of undetected paediatric patients at high cardiovascular risk might be greater than expected.
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Doenças Cardiovasculares/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Fatores de Risco de Doenças Cardíacas , Pais/psicologia , Prevenção Primária , Adulto , Feminino , Humanos , Recém-Nascido , Itália , MasculinoRESUMO
OBJECTIVE: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5(th) percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL. METHODS: A one month old infant with failure to thrive, severe hypocholesterolemia and acanthocytosis was clinically and genetically characterized. Molecular characterization of the proband and her parents was performed by direct sequencing of the APOB gene and functional role of the identified mutations was assessed by the minigene methodology. RESULTS: The proband was found carrying two novel splicing mutations of the APOB gene (c.3696+1G > C and c.3697-1G > A). CHOK1H8 cells expressing minigenes harbouring the mutations showed that these two mutations were associated with the retention of intron 23 and skipping of exon 24, resulting in two truncated apoB fragments of approximate size of 26-28 % of ApoB-100 and the total absence of apoB. CONCLUSION: We describe the first case of Ho-FHBL due to two splicing mutations affecting both the donor and the acceptor splice sites of the same intron of the APOB gene occurring in the same patient. The clinical management of the proband is discussed and a review of the clinical and genetic features of the published Ho-FHBL cases is reported.
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Apolipoproteína B-100/genética , Homozigoto , Hipobetalipoproteinemias/diagnóstico , Hipobetalipoproteinemias/genética , Mutação , Abetalipoproteinemia/genética , Adulto , Processamento Alternativo , Colesterol/sangue , LDL-Colesterol/sangue , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Íntrons , MasculinoRESUMO
Severe hypertriglyceridemia (sHTG) (plasma triglyceride level > 10 mmol/L) due to lipoprotein lipase (LPL) deficiency is a known risk factor for acute pancreatitis. A 23-day-old male with sHTG was admitted to the Neonatal Intensive Care Unit for plasmapheresis being at high risk for acute pancreatitis. Given the potential hazard of an extracorporeal technique in a very young infant, we decided to perform an exchange transfusion (ET), a procedure widely used by neonatologists and less invasive than plasmapheresis. ET led to a dramatic reduction in plasma triglyceride level, from 93.2 to 3.8 mmol/L at the end of the procedure, without adverse events. The subsequent administration of a special formula low in fat and high in medium-chain triglycerides was effective in keeping fasting plasma triglyceride level below 5.6 mmol/L during the first 5 months of life. The sequence of LPL gene revealed that the patient was apparently homozygous for a novel nucleotide deletion (c.840delG) in exon 6 leading to a premature termination codon (p.N281Mfs*23). However, family studies revealed that while the patient's mother was heterozygous for this mutation, the father was heterozygous for a novel deletion eliminating the whole LPL gene. The patient therefore turned out to be a compound heterozygous for two LPL gene mutations predicted to abolish LPL activity. This is the first case of sHTG treated with ET in a neonate reported in the literature. ET appears to be a safe procedure, alternative to plasmapheresis, to prevent acute pancreatitis in young infants with sHTG due to LPL deficiency.
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OBJECTIVE: To ascertain whether the molecular characterization of a defect in the low-density lipoprotein (LDL) receptor gene (LDLR) in children with heterozygous familial hypercholesterolemia (heFH) identifies subjects at greater risk of developing premature coronary artery disease (pCAD) later in life. STUDY DESIGN: We investigated 264 children with heFH from 201 families, along with 148 affected parents and 100 unaffected siblings. The lipid profile was assessed before any treatment was provided, and genotype analysis was performed to characterize LDLR defects. In a subgroup of children with heFH and controls, we measured aorta and carotid intima-media thickness (aIMT and cIMT). The prevalence of pCAD in parents and/or grandparents with heFH was recorded. RESULTS: The children with heFH with a family history of pCAD had higher LDL cholesterol and apolipoprotein B levels and greater aIMT and cIMT than those with negative family history. Compared with carriers of LDLR-defective mutations, carriers of LDLR-negative mutations had a more severe phenotype, in terms of plasma lipid levels and IMT, and a higher prevalence of pCAD in first-degree relatives (36% vs 6.7%; P < .001). CONCLUSIONS: The study of heFH in children, in which other risk factors for CAD play a minor role, allows early identification of those at increased risk for developing pCAD, who merit more stringent clinical control and early pharmacologic treatment.