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Hyperlipoproteinemia (HLP) is one of the most common metabolic disorder in childhood. We assume that 20 % of children have a disorder of the lipid metabolism. Some HLP are very common in the population, and moderate, and some are very rare, but are very severe. These may occur secondary to pathological conditions, or are formed on the basis of the primary monogenic or polygenic disorders of lipid metabolism. The detection of children with HLP in the Czech Republic is either random, or more often by selective screening of children with familial history of cardiovascular disease, provided by general pediatric practitioners for children and adolescents. Treatment in childhood is primarily dietetic, some of them, especially children with familial hypercholesterolemia are treated from 8-10 years pharmacologically.Key words: diagnosis - hyperlipoproteinemia - children - treatment.

Hyperlipoproteinemia (HLP) and dyslipidemia (DLP) are of course mainly perceived as diseases of common incidence and are typically seen as the greatest risk factors (RF) in the context of the pandemic of cardiovascular diseases. This is certainly true and HLP or DLP overall affect tens of percents of adults. However we cannot overlook the fact that disorders (mostly congenital) of lipid metabolism exist which, though not formally defined as such, amply satisfy the conditions for classification as rare diseases. Our account only includes a brief overview of the rare HLPs based on the dominant disorder of lipid metabolism, i.e. we shall mention the rare primary forms of hypercholesterolemia, primary forms of hypertriglyceridemia and the rare primary combined forms of HLP. In recent years an amazing progress has been reached relating to these diseases, in particular in the area of exact identification of the genetic defect and the mechanism of defect formation, however each of these diseases would require a separate article, though outside the field of clinical internal medicine. Therefore we shall discuss homozygous familial hypercholesterolemia (FH) in greater depth, partially also the "severe" form of heterozygous FH and in the following part the lipoprotein lipase deficiency; that means, diseases which present an extreme and even fatal risk for their carriers at a young age, but on the other hand, new therapeutic possibilities are offered within their treatment. An internist then should be alert to the suspicion that the described diseases may be involved, know about their main symptoms, where to refer the patient and how to treat them. Also dysbetalipoproteinemia (or type III HLP) will be briefly mentioned. Homozygous FH occurs with the frequency of 1 : 1 000 000 (maybe even more frequently, 1 : 160 000), it is characterized by severe isolated hypercholesterolemia (overall cholesterol typically equal to 15 mmol/l or more), xanthomatosis and first of all by a very early manifestation of a cardiovascular disease. Myocardial infarction is not an exception even in childhood. The therapy is based on high-dose statins, statins in combination with ezetimib and now also newly on PCSK9 inhibitors. Lomitapid and partly also mipomersen hold great promise for patients. LDL apheresis then represents an aggressive form of treatment. Lipoprotein lipase deficiency (type I HLP) is mainly characterized by severe hypertriglyceridemia, serum milky in colour, and xanthomatosis. A fatal complication is acute recurrent pancreatitis. A critical part of the treatment is diet, however it alone is not enough to control a genetic disorder. The only approved treatment is gene therapy. Experimentally, as an "off label" therapy, it is used in case studies with a lomitapid effect. We have our own experience with this experimental therapy. Dysbetalipoproteinemia is a congenital disorder of lipoprotein metabolism, characterized by high cholesterol (CH) and triglyceride (TG) levels. The underlying cause of this disease is the defect of the gene providing for apolipoprotein E. It is clinically manifested by xanthomatosis, however primarily by an early manifestation of atherosclerosis (rather peripheral than coronary).Key words: Lipoprotein lipase deficiency - dysbetalipoproteinemia - familial hypercholesterolemia - gene therapy - homozygous FH - LDL apheresis - lomitapid - mipomersen - PCSK9 inhibitors - rare diseases.

At present, literally no one disputes hyperlipoproteinaemia and dyslipidemia (HLP and DLP) treatment as a rational therapeutic approach in the prevention of cardiovascular diseases (CVD). This approach is in line with the current principles of evidence-based medicine (EBM) and is sufficiently evidenced particularly by the results of large intervention studies. Nevertheless! When the results of the recent studies are critically appraised, these by no means are (mostly, there, obviously, are exceptions) as conclusive as the studies conducted in 1980s and 1990s. Consequently, positive results are being sought in subanalyses, subgroup evaluations and multiple-study metaanalyses. This paper is not intended as a critique of new drugs. These certainly are developed to be safe, effective and well-tolerated. However, the newer studies suffer from a range of issues: the populations studied are already very well managed, it is not possible to compare against placebo and sometimes, let us be honest, the trial design itself is problematic (often it is an uncritical effort to treat as wide as possible range of patients as well as new groups of patients who might not be suitable for the given treatment). Certainly, we should not start disputing the well-evidenced hypotheses and seek alternatives to the long-established arguments and approaches as a consequence to some less convincing studies. We must not overlook the most robust results of statin studies as well as 'positive' studies with other hypolipidemics. There is no doubt that the effect ofstatins on LDL-cholesterol represents a significant move towards cardiovascular disease prevention. Despite this, we currently recognise with increased intensity that this very effective and well-evidenced treatment has its limits and that a high proportion of patients dies or are faced with cardiovascular diseases even though they are treated with a correct dose ofa statin and a target LDL-C level is achieved. This remaining risk (represents more than 50% ofevents) has been termed 'RESIDUAL RISK'. The issue of residual risk is crucial in patients with type 2 diabetes mellitus (DM2T) or in all patients with HDL-C-low DLP. As was repeatedly emphasised, a statin will be a cornerstone of pharmacological treatment of a DLP. However, a question arises what to combine it with. The most convincing data exist for niacin (combination of niacin with laropiprant minimising the incidence of unwanted flushes). We surely should not marginalize other hypolipidemics used mainly in combinations: resin and ezetimibe to treat LDL-C, niacin, fibrates and possibly omega-3-fatty acids to manage the residual risk (HDL and TG). Last but not least we should not forget non-pharmacological treatment as the pivotal treatment approach in all patients.

Elevated LDL-cholesterol levels and reduced HDL-cholesterol levels are independent risk factors for the development of ischaemic heart disease. Atherosclerosis is promoted also by some particles rich in triacylglycerols, in particular intermediate density lipoproteins (IDL), partly also very low density lipoproteins (VLDL). The risk of IHD is enhanced also by subfractions of LDLIII and protracted postprandial lipaemia, characterized by an increased concentration of remnants of chylomicrons. An independent risk factor is also an increased concentration of lipoprotein(a). When evaluating the cardiovascular risk of an actual patient it is always necessary to consider in addition to blood lipid levels also other non-lipid risk factors.

Unlabelled: Our study focused on the effect of non-pharmacological intervention based on the modification of dietary habits and increasing physical activity on the level of total plasma cholesterol., Sample and Methods: Intervented sample was created by 279 highly motivated healthy adults from Brno (168 women and 111 men) of average age 43.5 +/- 10.3 years and average level of total plasma cholesterol 6.1 +/- 0.75 mmol/l and HDL-cholesterol 1.04 +/- 0.14 mmol/l. After medical and life-style history assessment, followed by clinical and biochemical checking and evaluation the risk from the life-style and biochemical and clinical parameters, the participants were individually informed about recommendations. These recommendations regarded detailed changes of dietary habits, quantified by the recommended number of servings of basic food groups and sub-groups daily and also increasing physical activity., Results: After 3 months the changes of biochemical parameters were evaluated. After our non-pharmacological intervention we founded significantly lower average level of total plasma cholesterol 5.36 +/- 1.24 mmol/l (p < 0.001) and higher level of HDL-cholesterol 1.16 +/- 0.14 mmol/l. The level of TG's did not change significantly neither in whole sample, nor in the sub/sample of women and men. 26% of our sample was resistant to the intervention (the difference in the total cholesterol level between 2 assessment was lower than 0.5 mmol/l). No significant difference was found between men and women regarding the reaction of plasma lipoproteins., Discussion and Conclusions: Our results justify the adequacy and appropriety of primary preventive advising focusing on decrease of the risk of premature death using non-pharmacological intervention in highly motivated people with good compliance and sufficient responsibility for their personal health.

There are sufficient arguments for treatment of hyperlipoproteinaemia at present and this treatment is considered not only rational but also an essential procedure in primary and in particular in secondary prevention of cardiovascular diseases. Views of scepticists as regards this treatment are, with regard to the most recent epidemiological studies with hypolipidaemic agents, not very convincing and the majority is refused. Treatment of patients with hyperlipoproteinaemia is comprehensive, its basis being dietary and lifestyle measures. The latter are, if they are not sufficiently effective, with increasing frequency supplemented with medicamentous intervention. This treatment is then as a rule very effective and leads to rapid achievement of desirable "target values" of parameters of lipid and lipoprotein metabolism. This comprehensive therapeutic algorithm is considered the modern approach to primary and secondary prevention of cardiovascular diseases. If a long-term favourable effect on the lipid spectrum is to be achieved in individual subjects and whole populations (and in particular in populations of subjects with the highest risk of manifestation of complications of atherosclerosis), it is essential to implement the mentioned therapeutic measures on a long-term basis, frequently for the rest of life. Considering contemporary prices of medicaments which are used to influence risk factors of atherosclerosis, this quite understandably worries health economists. Despite their "economic" objections it is important to give maximal support to preventive measures. Therapeutic procedures in advanced disease may be finally incomparably more expensive than soundly implemented preventive measures. On the other hand, it is a must to treat disorders of the lipid metabolism, as well as other risk factors of atherosclerosis such as hypertension or diabetes mellitus rationally, respecting recent results of basic and applied research. It is also a great advantage if we can use as a basis for the diagnostic and therapeutic algorithm international widely accepted recommendations of European and American societies. We also use their recommendations as guidelines when seeking the right patient or group of subjects on whom our greatest therapeutic effort should be focused.

The author reviews the main epidemiological studies which identified a number of risk factors of ischaemic heart disease and became the basis for widely accepted ranges of lipids where dietary or medicamentous intervention should be used. She emphasizes in particular the evaluation of the total risk not only from the aspect of various lipid indicators but also non-lipid risk factors. The author reviews the main hypolipidaemic intervention studies and their meta-analyses. She emphasizes the importance of hitherto not widely accepted hypolipidaemic treatment in secondary prevention of ischaemic heart disease, which reduced not only cardiovascular but also total mortality. The author gives also an account of coronarography-based intervention studies which provide evidence that intensive hypolipidaemic treatment leads not only to arrested progression but may induce regression of atherosclerotic vascular changes.

The authors administered to a group of 60 patients with primary hyperlipoproteinaemia (HLP) HLP type IIA 9, IIB 16, type IV 35 (fish oil) (Activepa 30TG) rich in eicosapentaenic acid (EPA, 20:5-n-3) and docosahexaenic acid (DHA, 22:6n-3). Administration of fish oil, 10 g per day, for a period of 21 days led to a decline of the total cholesterol by 9.8%, triglycerides (TG) by 39.5% and a rise of HDL-cholesterol (HDL-C) by 12.8%. The concentration of LDL-C, apo B, and apo A-I did not change significantly. The content of individual fatty acids (FA) in phosphatidyl choline (PC) cholesteryl esters (CE) and plasma TG before treatment was used as an independent variable for discrimination analysis in relation to dependent variables such quintile 1 (Q1) and Q2 on the one hand and Q4 and Q5 differences of the above mentioned parameters on the other hand. The drop of TG after ingestion of n-3 FA correlates indirectly with concentrations of PC 20:5n-3, TG 18:3n-3 and TG 20:4n-6. The content of 20:0 and 20:1 in PC and 18:0 in TG are related to the rise of LDL-C after treatment. The drop of apo B is associated with the PC 22:6n-3 concentration. The rise of HDL-C and apo A-I is positively associated with the concentration of 16:1n-7 in PC and TG and negatively with the CE 16:0 content. The rise of HDL-C after treatment is moreover negatively influenced by concentrations of PC 18:3n-6 and TG 20:3n-6.(ABSTRACT TRUNCATED AT 250 WORDS)