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BACKGROUND: Forkhead box protein 3 (FOXP3) is the master transcription factor in CD4+CD25hiCD127lo regulatory T (Treg) cells. Mutations in FOXP3 result in IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome. Clinical presentation of IPEX syndrome is broader than initially described, challenging the understanding of the disease, its evolution, and treatment choice. OBJECTIVE: We sought to study the type and extent of immunologic abnormalities that remain ill-defined in IPEX, across genetic and clinical heterogeneity. METHODS: We performed Treg-cell-specific epigenetic quantification and immunologic characterization of severe "typical" (n = 6) and "atypical" or asymptomatic (n = 9) patients with IPEX. RESULTS: Increased number of cells with Treg-cell-Specific Demethylated Region demethylation in FOXP3 is a consistent feature in patients with IPEX, with (1) highest values in those with typical IPEX, (2) increased values in subjects with pathogenic FOXP3 but still no symptoms, and (3) gradual increase over the course of disease progression. Large-scale profiling using Luminex identified plasma inflammatory signature of macrophage activation and TH2 polarization, with cytokines previously not associated with IPEX pathology, including CCL22, CCL17, CCL15, and IL-13, and the inflammatory markers TNF-α, IL-1A, IL-8, sFasL, and CXCL9. Similarly, both Treg-cell and Teff compartments, studied by Mass Cytometry by Time-Of-Flight, were skewed toward the TH2 compartment, especially in typical IPEX. CONCLUSIONS: Elevated TSDR-demethylated cells, combined with elevation of plasmatic and cellular markers of a polarized type 2 inflammatory immune response, extends our understanding of IPEX diagnosis and heterogeneity.
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Enfermedades Genéticas Ligadas al Cromosoma X , Poliendocrinopatías Autoinmunes , Humanos , Factores de Transcripción Forkhead , Linfocitos T Reguladores , Mutación , Epigénesis GenéticaRESUMEN
PURPOSE OF REVIEW: Insulin resistance (IR) is a clinical condition due to the decline in the efficiency of insulin promoting glucose uptake and utilization. The aim of this review is to provide an overview of the current knowledge on IR in children, focusing on its physiopathology, the most appropriate methods of measurement of IR, the assessment of risk factors, the effects of IR in children, and finally giving indications on screening and treatment. RECENT FINDINGS: IR has evolved more and more to be a global public health problem associated with several chronic metabolic diseases. SUMMARY: Detecting a correct measurement method and specific risk predictors, in order to reduce the incidence of IR, represents a challenging goal.
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Resistencia a la Insulina , Glucemia/metabolismo , Índice de Masa Corporal , Niño , Humanos , Incidencia , Insulina/uso terapéutico , Factores de RiesgoRESUMEN
Insulin resistance (IR) is a key component in the etiopathogenesis of hypertension (HS) in patients with diabetes mellitus (DM). Several pathways have been found to be involved in this mechanism in recent literature. For the above-mentioned reasons, treatment of HS should be specifically addressed in patients affected by DM. Two relevant recently published guidelines have stressed this concept, giving specific advice in the treatment of HS in children belonging to this group: the European Society of HS guidelines for the management of high blood pressure in children and adolescents and the American Academy of Pediatrics Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents. Our aim is to summarize the main pathophysiological mechanisms through which IR causes HS and to highlight the specific principles of treatment of HS for children with DM.
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Hipertensión , Resistencia a la Insulina , Adolescente , Niño , Humanos , Hipertensión/complicaciones , Hipertensión/terapia , Tamizaje Masivo , Estados UnidosRESUMEN
PURPOSE OF REVIEW: It is well known that obesity represents the main modifiable risk factor for insulin resistance in children and adolescents; obesity-induced insulin resistance in children is the most important risk factor for developing cardiovascular diseases and type 2 diabetes in adulthood. The mechanisms through which obesity causes insulin resistance are complex and not completely known to date. RECENT FINDINGS: In children, global adiposity is the main factor determining insulin resistance. Excessive fatty acids play a determinant role in the pathogenesis of insulin resistance in obese children, inducing an increased production of acetyl-CoA in the liver and enhancing inflammation in adipose tissue. The aetiology of insulin resistance in polycystic ovary syndrome is multifactorial and still debated. SUMMARY: The aim of this review is to present an updated frame and new insights of the numerous pathways involved in the development of insulin resistance in obese patients, focusing on the peculiarities of children and adolescents. Improving the knowledge of mechanisms through which obesity leads to insulin resistance is fundamental in order to recommend particular follow-up and possible treatment to specific categories of obese children and adolescents.
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Diabetes Mellitus Tipo 2/complicaciones , Resistencia a la Insulina , Obesidad/complicaciones , Síndrome del Ovario Poliquístico/complicaciones , Adiposidad/fisiología , Adolescente , Adulto , Composición Corporal , Niño , Femenino , Intolerancia a la Glucosa/complicaciones , HumanosRESUMEN
Anthropologists are frequently required to confirm or exclude the human origin of skeletal remains; DNA and protein radioimmunoassays are useful in confirming the human origin of bone fragments but are not always successful. Histology may be the solution, but the young subadult structure could create misinterpretation. Histological tests were conducted on femur and skull of 31 human subjects. Each sample was observed focusing on presence or absence of fibrous bone, lamellar bone, radial lamellar bone, plexiform bone, reticular pattern, osteon banding, Haversian bone, primary osteons, secondary osteon and osteon fragments. Samples were divided into five age classes; 1 (<1 year), 2 (1-5 years), 3 (6-10 years), 4 (11-15 years) and 5 (16-20 years). Regarding femurs, class 1 presented the following: 87.5% fibrous bone, 37.5% plexiform bone, 12.5% reticular pattern and 12.5% lamellar bone radially oriented. Class 2 showed 37.5% of fibrous bone, 12.5% of reticular pattern and 37.5% of osteon banding. In the higher age classes, the classical human structures, lamellar bone and osteons were frequently visible, except for one case of reticular pattern, generally considered a distinctive non-human structure. The situation appeared different for the skull, where there was a lack of similar information, both in human and non-human. An analysis of the percentage of lamellar bone and osteons was conducted on femur and skull fragments. A trend of increase of primary osteon number and a decrease of the lamellar bone area has been detected in the femur. The present study has therefore shed some light on further pitfalls in species determination of subadult bone.
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Fémur/patología , Cráneo/patología , Adolescente , Niño , Preescolar , Antropología Forense/métodos , Osteón/patología , Humanos , Lactante , Especificidad de la Especie , Adulto JovenRESUMEN
Hypertension is a real problem in children. It shows a tracking behaviour, representing a key risk factor for hypertension, cardiovascular disease, and end-organ failure in adulthood. However, the importance of addressing arterial hypertension in children is not limited to its risk of tracking into adulthood. Thus, early detection and management are crucial. Hypertension may be primary or due to secondary causes, and identification of this distinction is very important for the treatment setting. Importantly, the management of hypertension in children is crucial to prevent the well-known cardiovascular effects in adulthood. As demonstrated in the literature, healthy eating habits, together with regular physical activity, can have a major impact on reducing high blood pressure and preventing organ damage in children and adolescents. However, suppose these are not sufficient to treat hypertension. In that case, if patients are symptomatic and/or have additional metabolic conditions such as obesity, type diabetes mellitus, or chronic kidney disease, anti-hypertensive medication must be started. Recent guidelines have provided clear guidance on the treatment of hypertension and hypertensive crisis in pediatric age. On the other hand, there are currently few specific recommendations on the treatment of isolated nocturnal hypertension and treatment-resistant hypertension. This review aims to summarize the most recent recommendations for the treatment of hypertension and hypertensive crisis in children and the last years' knowledge and experience in treating childhood isolated nocturnal hypertension and resistant hypertension of childhood.
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Neurodegenerative disorders are a group of diseases characterized by progressive degeneration of the nervous system, leading to a gradual loss of previously acquired motor, sensory and/or cognitive functions. Leukodystrophies are amongst the most frequent childhood-onset neurodegenerative diseases and primarily affect the white matter of the brain, often resulting in neuro-motor disability. Notably, gastrointestinal (GI) symptoms and complications, such as gastroesophageal reflux disease (GERD) and dysphagia, significantly impact patients' quality of life, highlighting the need for comprehensive management strategies. Gut dysbiosis, characterized by microbial imbalance, has been implicated in various GI disorders and neurodegenerative diseases. This narrative review explores the intricate relationship between GI symptoms, Gut Microbiota (GM), and neurodegeneration. Emerging evidence underscores the profound influence of GM on neurological functions via the microbiota gut-brain axis. Animal models have demonstrated alterations in GM composition associated with neuroinflammation and neurodegeneration. Our single-centre experience reveals a high prevalence of GI symptoms in leukodystrophy population, emphasizing the importance of gastroenterological assessment and nutritional intervention in affected children. The bidirectional relationship between GI disorders and neurodegeneration suggests a potential role of gut dysbiosis in disease progression. Prospective studies investigating the GM in leukodystrophies are essential to understand the role of gut-brain axis dysfunction in disease progression and identify novel therapeutic targets. In conclusion, elucidating the interplay between GI disorders, GM, and neurodegeneration holds promise for precision treatments aimed at improving patient outcomes and quality of life.
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Advancements in food science technology have allowed the development of new products for the therapeutic management of inherited metabolic diseases such as phenylketonuria (PKU). Glycomacropeptide (GMP), a peptide derived from casein, is naturally low in phenylalanine (Phe) and, thus, adequate for protein substitutes (PSs) for the management of PKU in children. This review aims primarily to analyse the differences in the nutritional composition of GMP-based protein substitutes in different formulations (ready to drink, powdered, and bars), and secondarily to assess the quality of these products, comparing their nutritional composition with that of standard amino acid (L-AA) mixtures. Thirty-five GMP-based PSs produced by six different companies were included in this review: twenty-one powdered PSs, eight ready to drink, and six bars. The analysis revealed great heterogeneity not only among the different formulations (powdered, ready to drink, and bars) but also within the same group, in terms of energy content and nutritional composition. GMP-based PSs were shown to have higher contents of sugars and saturated fatty acids compared to L-AA PSs, especially in ready-to-drink formulations and bars. The latter also provided the highest amounts of energy among the GMP-based products. This finding may be related to a higher risk of developing overweight and obesity. The greater palatability of these GMP-based PSs, combined with improved nutritional quality, could not only improve adherence to diet therapy but also reduce the incidence of obesity-related comorbidities in PKU.
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Caseínas , Fragmentos de Péptidos , Fenilcetonurias , Niño , Humanos , Italia , ObesidadRESUMEN
Pulmonologists may be involved in managing pulmonary diseases in children with complex clinical pictures without a diagnosis. Moreover, they are routinely involved in the multidisciplinary care of children with rare diseases, at baseline and during follow-up, for lung function monitoring. Lysosomal storage diseases (LSDs) are a group of genetic diseases characterised by a specific lysosomal enzyme deficiency. Despite varying pathogen and organ involvement, they are linked by the pathological accumulation of exceeding substrates, leading to cellular toxicity and subsequent organ damage. Less severe forms of LSDs can manifest during childhood or later in life, sometimes being underdiagnosed. Respiratory impairment may stem from different pathogenetic mechanisms, depending on substrate storage in bones, with skeletal deformity and restrictive pattern, in bronchi, with obstructive pattern, in lung interstitium, with altered alveolar gas exchange, and in muscles, with hypotonia. This narrative review aims to outline different pulmonary clinical findings and a diagnostic approach based on key elements for differential diagnosis in some treatable LSDs like Gaucher disease, Acid Sphingomyelinase deficiency, Pompe disease and Mucopolysaccharidosis. Alongside their respiratory clinical aspects, which might overlap, we will describe radiological findings, lung functional patterns and associated symptoms to guide pediatric pulmonologists in differential diagnosis. The second part of the paper will address follow-up and management specifics. Recent evidence suggests that new therapeutic strategies play a substantial role in preventing lung involvement in early-treated patients and enhancing lung function and radiological signs in others. Timely diagnosis, driven by clinical suspicion and diagnostic workup, can help in treating LSDs effectively.
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Olipudase alfa is indicated for the non-central nervous system manifestations of Acid sphingomyelinase deficiency (ASMD). Anaphylaxis is a very rare and life-threatening adverse reaction described for this drug. Here, we report the case of a 2-year-old boy affected by chronic neurovisceral ASMD who experienced signs of hypersensitivity reactions to olipudase alfa since the administered dose of 1 mg/kg during dose escalation and a proper anaphylactic reaction during the second administration of the target therapeutic dose of 3 mg/kg. The treatment was stopped for 15 weeks and then a 7-step desensitization protocol with the infused dose of 0.03 mg/kg was applied. Subsequent gradual dose escalation was resumed, successfully reaching the dose of 0.3 mg/kg. Moreover, biochemical, and radiological disease indexes, which were increased during treatment discontinuation, have gradually improved since the restart of treatment. However, at the second administration of the dose of 0.6 mg/kg, the patient experienced another adverse drug reaction with facial urticarial rash and bronchospasm, requiring the administration of adrenaline, methylprednisolone, and inhaled salbutamol. This case report highlights the need to customize the olipudase alfa desensitization protocol according to individual tolerance and raises the issue of achieving the established therapeutic target in the most sensitive children. Synopsis: We report a case of anaphylaxis to olipudase alfa in a child affected by chronic neurovisceral Acid sphingomyelinase deficiency (ASMD) and describe a 7-step desensitization procedure. This procedure, with the total administered dose of 0.03 mg/kg, followed by gradual dose escalation, allowed to reach the dose of 0.3 mg/kg without adverse reactions; however, at the second administration of the dose of 0.6 mg/kg our patient presented another adverse reaction suggesting the need of a different desensitization strategy.
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BACKGROUND: Limited evidence exists regarding the association between COVID-19 and Long COVID manifestations in children, particularly concerning variants of concern (VOCs). We aimed to characterize a cohort of pediatric patients hospitalized with confirmed acute SARS-CoV-2 and monitor them for Long COVID symptoms. Additionally, it seeks to explore any potential correlations between VOCs and clinical symptoms. METHODS: We conducted a prospective study involving children hospitalized from November 2021 to March 2023, with confirmed acute SARS-CoV-2 infection. A telephone survey was conducted at 3-6-12 months after discharge. RESULTS: We included 167 patients (77 F/90 M). Upon hospital admission, 95.5% of patients presented as symptomatic. Regarding patients for whom it was feasible to determine the SARS-CoV-2 variant (n = 51), the Delta variant was identified in 11 children (21.6%) and Omicron variant in the remaining 40 patients (78.4%: 27.5% BA.1 variant; 15% BA.2 variant; 57.5% BA.5 variant). 19 patients (16.5%) reported experiencing at least one symptom indicative of Long COVID (weight loss 31.6%, inappetence 26.3%, chronic cough 21.1%, fatigue 21.1%, and sleep disturbances, wheezing, abdominal pain and mood disorders 15.8%). In only 4 patients with Long COVID we could identified a specific SARS-CoV-2 variant (3 Omicron: 2 BA.1 and 1 BA.2; 1 Delta). CONCLUSIONS: this study underscores that long COVID is a significant concern in the pediatric population. Our data reinforce the importance of continuously monitoring the impact of long-COVID in infants, children, and adolescents. A follow-up following SARS-CoV-2 infection is therefore advisable, with symptom investigation tailored to the patient's age.
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COVID-19 , Niño Hospitalizado , Adolescente , Lactante , Humanos , Niño , SARS-CoV-2 , COVID-19/epidemiología , Síndrome Post Agudo de COVID-19 , Estudios Prospectivos , Italia/epidemiologíaRESUMEN
Over the last few decades, numerous scientific studies have investigated the possible association between sleep duration and adiposity during childhood, since it has been reported that sleep deprivation causes a related increase in caloric intake. Even though the underlying pathogenetic mechanisms are still under study and not completely known, the effect of dietetic habits and nutrient intake on sleep quality and patterns has been reported. The aim of this study is to explore the intricate interplay between food intake/diet patterns and pediatric sleep disturbances in children and adolescents with obesity, emphasizing the importance of not underestimating this aspect in the prevention and treatment of this complex disease. Recent evidence supports a high correlation between specific diet patterns and foods with sleep disturbances in children at all ages. Diets rich in fiber, fruit, vegetables, and anti-inflammatory nutrients and low in saturated fats seem to promote better sleep quality. Sleep disturbances are, in turn, risk factors for the development of obesity. Therefore, food strategies should be applied to counteract this harmful process. Unraveling the complex links between dietary habits, sleep patterns, and obesity is essential for developing effective strategies to combat this critical public health issue.
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Obesidad Infantil , Adolescente , Humanos , Niño , Obesidad Infantil/complicaciones , Obesidad Infantil/epidemiología , Dieta/efectos adversos , Ingestión de Energía , Frutas , Privación de Sueño/complicaciones , Conducta Alimentaria , Ingestión de Alimentos , Fibras de la Dieta , SueñoRESUMEN
Evidence suggests that psychological and physical stress are relevant triggering factors for the onset of type 1 diabetes (T1D) and type 2 diabetes (T2D). The underlying mechanisms involve a complex neuroendocrine structure, involving the central nervous system and the periphery. Psychological stress leads to an increase of serum glucocorticoid concentrations and catecholamines release increasing the insulin need and the insulin resistance. According to the ß-cell stress hypothesis, also causes of increased insulin demand, such as rapid growth, overweight, puberty, low physical activity, trauma, infections, and glucose overload, are potentially relevant factors in development of T1D. It has also been demonstrated that chronic stress and obesity form a vicious circle which leads to a definitive metabolic failure, increasing the risk of developing T2D. In this review, we will provide the most recent data concerning the role of stress in the outcomes of T1D and T2D, with a focus on the role of physical and psychological stress on the onset of T1D.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 1/etiología , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/etiología , Insulina , Resistencia a la Insulina/fisiología , GlucosaRESUMEN
Pubertal development represents the process of physical maturation where an adolescent reaches sexual maturity and attains reproductive function. The effects of vitamin D are mainly mediated by the vitamin D receptor (VDR), which is expressed in almost all body cells, including the ovary and human pituitary gland and animal hypothalamus. Thus, vitamin D has gained great interest as pathogenic factor of pubertal disorders and fertility. This narrative review aimed to provide a broad overview of the available literature regarding the association between vitamin D levels, puberty timing, and age at menarche. A review of the data on the involvement of micronutrient deficiency, as a modifiable cause of pubertal disorders, is important for the prediction and prevention of deficiencies as well as for fertility protection and should be considered a public health priority. Reported data support that vitamin D is a regulator of neuroendocrine and ovarian physiology and, more in detail, a deficiency of vitamin D is involved in altered pubertal timing. Considering the long-term consequences of early pubertal development and early menarche, the detection of modifiable causes is crucial in preventive strategies. Future studies in humans and with an increased scale are needed to elucidate the vitamin D role in sexual maturation and puberty development.
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Since the advent of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increased incidence of several endocrinological anomalies in acute-phase and/or long-term complications has been described. The aim of this review is to provide a broad overview of the available literature regarding changes in the worldwide epidemiology of endocrinological involvement in children since December 2019 and to report the evidence supporting its association with coronavirus disease 2019 (COVID-19). Although little is known regarding the involvement of endocrine organs during COVID-19 in children, the current evidence in adults and epidemiological studies on the pediatric population suggest the presence of a causal association between the virus and endocrinopathies. Untreated transient thyroid dysfunction, sick euthyroid syndrome, nonthyroidal illness syndrome, and hypothalamic-pituitary-adrenal (HPA) axis and central precocious puberty have been observed in children in acute infection and/or during multisystem inflammatory syndrome development. Furthermore, a higher frequency of ketoacidosis at onset in children with a new diagnosis of type 1 diabetes is reported in the literature. Although the direct association between COVID-19 and endocrinological involvement has not been confirmed yet, data on the development of different endocrinopathies in children, both during acute infection and as a result of its long-term complications, have been reported. This information is of primary importance to guide the management of patients with previous or current COVID-19.
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Inflammatory status is one of the main drivers in the development of non-communicable diseases (NCDs). Specific unhealthy dietary patterns and the growing consumption of ultra-processed foods (UPFs) may influence the inflammation process, which negatively modulates the gut microbiota and increases the risk of NCDs. Moreover, several chronic health conditions require special long-term dietary treatment, characterized by altered ratios of the intake of nutrients or by the consumption of disease-specific foods. In this narrative review, we aimed to collect the latest evidence on the pro-inflammatory potential of dietary patterns, foods, and nutrients in children affected by multifactorial diseases but also on the dietetic approaches used as treatment for specific diseases. Considering multifactorial diet-related diseases, the triggering effect of pro-inflammatory diets has been addressed for metabolic syndrome and inflammatory bowel diseases, and the latter for adults only. Future research is required on multiple sclerosis, type 1 diabetes, and pediatric cancer, in which the role of inflammation is emerging. For diseases requiring special diets, the role of single or multiple foods, possibly associated with inflammation, was assessed, but more studies are needed. The evidence collected highlighted the need for health professionals to consider the entire dietary pattern, providing balanced and healthy diets not only to permit the metabolic control of the disease itself, but also to prevent the development of NCDs in adolescence and adulthood. Personalized nutritional approaches, in close collaboration between the hospital, country, and families, must always be promoted together with the development of new methods for the assessment of pro-inflammatory dietary habits in pediatric age and the implementation of telemedicine.
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Dieta , Enfermedades Inflamatorias del Intestino , Adulto , Adolescente , Humanos , Niño , Nutrientes , Dieta Saludable , Enfermedades Inflamatorias del Intestino/etiología , InflamaciónRESUMEN
In our modern society, where highly palatable and calorie-rich foods are readily available, and sedentary lifestyle is common among children and adolescents, we face the pandemic of obesity, nonalcoholic fatty liver disease, hypertension, atherosclerosis, and T2D. Insulin resistance (IR) is known to be the main underlying mechanism of all these associated health consequences; therefore, the early detection of IR is fundamental for preventing them.A Consensus Statement, internationally supported by all the major scientific societies in pediatric endocrinology, was published in 2010, providing all the most recent reliable evidence to identify the definition of IR in children, its measurement, its risk factors, and the effective strategies to prevent and treat it. However, the 2010 Consensus concluded that further research was necessary to assess some of the discussed points, in particular the best way to measure insulin sensitivity, standardization of insulin measurements, identification of strong surrogate biomarkers of IR, and the effective role of lifestyle intervention and medications in the prevention and treatment of IR.The aim of this review is to update each point of the consensus with the most recent available studies, with the goal of giving a picture of the current state of the scientific literature regarding IR in children, with a particular regard for issues that are not yet fully clarified.
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Aterosclerosis , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Adolescente , Niño , Humanos , Consenso , ObesidadRESUMEN
Lipodystrophy includes a heterogeneous group of rare diseases characterized by different amounts of adipose tissue loss and several metabolic complications, including hypertriglyceridemia, steatohepatitis and particularly insulin resistance, that may lead to severe morbidity and, sometimes, mortality. Therefore, therapy for lipodystrophy primarily consists of a conventional approach that involves standard treatments of metabolic abnormalities. Given the evidence of leptin deficiency in lipodystrophy syndromes, leptin replacement therapy has been considered as a treatment option. Long-term studies on the use of therapy with a methionylated analog of human leptin, metreleptin, first on animals and subsequently on human patients, demonstrated enormous improvements of patients' clinical features and metabolic conditions. Recently, metreleptin was approved by Food and Drug Administration (FDA) for the treatment of generalized lipodystrophy and by European Medicines Agency (EMA) for the treatment of both generalized and partial lipodystrophy. However, further research is being conducted for new and different therapeutic agents, especially helpful for the treatment of patients with partial lipodystrophy, as some of them do not have access to metreleptin therapy or show poor response.
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Resistencia a la Insulina , Lipodistrofia Generalizada Congénita , Lipodistrofia , Animales , Humanos , Leptina/uso terapéutico , Lipodistrofia/tratamiento farmacológico , Lipodistrofia Generalizada Congénita/tratamiento farmacológico , Estados UnidosRESUMEN
Familial hypercholesterolemia is a common autosomal hereditary disorder characterized by elevated concentrations of low-density lipoprotein cholesterol and the development of premature atherosclerosis and cardiovascular disease. Early diagnosis, as well as prompt and aggressive treatment, are fundamental steps to prevent cardiovascular complications and a high rate of premature mortality in children and adolescents. Clinics and genetics are the two main aspects on which diagnosis is based. Widespread screening programs are a respectable option for the early detection of familial hypercholesterolemia. Different types of screening have been proposed so far; however, the optimal screening program has not yet been found. The treatment approach for both heterozygous and homozygous familial hypercholesterolemia in the pediatric population is multidisciplinary, including lifestyle modifications, standard lipid-lowering medications, and novel pharmacological agents. The latter show promising results, especially for patients who experience intolerance to other treatment or present with more severe conditions. Our purpose is to focus on the importance of the early detection of familial hypercholesterolemia, and to highlight the best therapeutic strategies, including the recent approaches based on current clinical evidence, that need to be adopted from the earliest stages of life.
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Cardiovascular diseases are the main causes of death and health costs in developed countries. Although cardiovascular diseases are thought to affect only adulthood, the underlying process of atherosclerosis begins in the first decade of life. Epidemiological studies show that severity of atherosclerosis depends both on the number and intensity of risk factors. Early detection of cardiovascular risk in childhood is the most powerful tool to prevent cardiovascular accidents in adulthood and possibly reduce its consequent burden for the future.A large amount of cardiovascular risk factors is already detectable in childhood and include non-modifiable elements, among which genetic factors and congenital heart diseases, and modifiable elements, which depend on environmental effects (e.g. lifestyle and nutrition). Regardless of the possibility to intervene on these factors, an early diagnosis is fundamental to ensure an optimal life expectancy in adulthood. The most important cardiovascular risk factors in the paediatric age and adolescence are excess weight, arterial hypertension, glucose metabolism and lipid metabolism alterations.In this review we will discuss the main risk factors strictly correlated with cardiac and vessels diseases, focusing on their pathogenesis, diagnosis, and treatments.