Primary giperlipoproteinemiya - Dislipidemiya (dislipoproteinemiya)

Primary giperlipoproteinemiya it is possible to classify as follows (tab. 2).

Family hypercholesterolemia

Family hypercholesterolemia —   the disease caused by defect of the gene coding synthesis, structure and function of a receptor to aproteina V/E and, therefore, to LPNP-to receptors.

Tab. 2. Classification of primary giperlipoproteinemiya (Ginsberg, Goldberg, 1998, with amendment)

Notes:
* Inclusion of family LP (a) - a giperlipoproteinemiya in group of the isolated hypercholesterolemia in a certain measure is conditional since at this type of giperlipoproteinemiya also the gipertriglitseridemiya can be observed (not always). The place of LP (a) is final - giperlipoproteinemiya in classification it is not defined, perhaps, it should be considered absolutely separately.

Now more than 300 various mutations in the field of this gene which are subdivided into 5 classes are known. Mutations of the first class result in the lowered concentration of MRNK of a receptor of LPNP in the patient's cells; mutations of the second class cause delay of transport       of protein from the place of synthesis to a cell membrane; mutations of the third class cause decline in the ability of a receptor to connect LPNP ligand; mutations of the fourth class cause disturbance of penetration in a cell of LPNP connected with a receptor; at a mutation of the fifth class formation of the shortened protein of the LPNP-receptor which is incapable to release a ligand in a cell that leads to degradation of a receptor is observed.
Distinguish two forms of a family hypercholesterolemia: heterozygous and homozygous.
The heterozygous form of a family hypercholesterolemia meets frequency of 1 a case on           the person in the general population, at the same time only a half of LPNP-receptors is functionally full. Main manifestations of a heterozygous form following:
xanthomatosis of sinews (Achilles tendon, and also area of a razgibately brush);

prematurity of atherosclerosis of coronary arteries and ischemic heart disease at the age of      years;
the hypercholesterolemia (from the moment of the birth), cholesterol level in blood raises to 7 — 13 mmol/l;

The homozygous form of a family hypercholesterolemia meets frequency of 1 a case on 1 — 1.5 million people. At this form of a disease           almost completely are absent or do not function.
Main symptoms of a disease following:

emergence of eruptive xanthomas on buttocks, elbows, knees, a mucous membrane of an oral cavity;
adjournment of lipids on the edge of an iris of the eye is observed aged till 30 flyings;
very much a prematurity of atherosclerosis and an ischemic heart disease (aged till 20 flyings, sometimes even in the first years
sharply expressed hypercholesterolemia (content of cholesterol in blood usually exceeds 13 mmol/l);

Patients with a homozygous form of a hypercholesterolemia die, as a rule, early, aged till 30 flyings of coronary heart disease.

Family defect of V-100 apoprotein

Family defect of V-100 apoprotein — the autosomal and dominant genetic disease which is characterized by reduction of affinity of LPNP to receptors V/E (to receptors to LPNP and LPPP). Nature of defect consists in a dot mutation of the gene coding synthesis of receptors V/E owing to what in situation 3500 there is a replacement of arginine by glutamine.
The clinical picture of defect of V-100 apoprotein is similar to clinic of a family hypercholesterolemia. At patients with this disease atherosclerosis of arteries of various localization and an ischemic heart disease early develop. It is promoted also by increase in the period of semi-life of LPNP and more expressed their ability to modification in comparison with the patients who do not have this genetic defect of V-100 apoprotein. Unlike a family hypercholesterolemia, at defect of V-100 apoprotein usually there are no tendinous xanthomas. The hypercholesterolemia fluctuates within 7 — 13 mmol/l, IIA hypercholesterolemia type comes to light.

Polygenic hypercholesterolemia

The polygenic hypercholesterolemia is the form of a hypercholesterolemia caused by the combined effect of defective proteins of several genes and additional influence of some external factors (the use of plentiful greasy food with high content of cholesterol and saturated animal fats, a hypodynamia). This form of a hypercholesterolemia is considered the most widespread.
Main manifestations of a polygenic hypercholesterolemia:
prematurity of atherosclerosis of arteries, including ischemic heart disease;
otlozheniyelipid on edge of an iris of the eye;
lack of xanthomas;
increase of content in cholesterol blood, is more often within 6.5 — 9.0 mmol/l;
type IIA giperlipoproteinemiya;
frequent detection of a hypercholesterolemia among members of the family of the patient.
In recent years there were messages that in a pathogeny of a polygenic hypercholesterolemia pathology of the genes responsible for synthesis of cholesterol and bile acids can matter (Ginsberg, Goldberg, 1998).

Family LP (a) - a giperlipoproteinemiya

Family LP (a) - giperlipoproteinemiyakhl ra ktorisutsya by high content in LP (a) blood that usually is followed by increase of the LPNP level and cholesterol, and also development of giperli-poproteinemiya IIA. High level in LP (a) blood always correlates with high risk of development of an ischemic heart disease.

Family gipertriglitseridemiya

Family gipertriglitseridemiya — the autosomal and dominant disease which is characterized by increase of content of triglycerides in blood. The mutations of genes which are the cornerstone of this disease are not identified. The pathogeny of an illness consists, on the one hand, in decrease in a catabolism of the lipoproteins rich with triglycerides, with another — in hyperproduction of LPONP. The family gipertriglitseridemiya meets frequency of 1 a case on 300 people in population and is characterized by high content in blood of triglycerides (2.8 — 8.5 mmol/l), giperlipoproteinemiy the IV type. (increase in blood of quantity of LPONP). The disease usually proceeds without the expressed clinical manifestations though at many patients symptoms of atherosclerosis of peripheral arteries are observed. However it develops slowly, the risk degree of a prematurity of an ischemic heart disease is not high. Nevertheless, Carlson (1979) proved a high risk of development of an ischemic heart disease at a family gipertriglitseridemiya.
At a family gipertriglitseridemiya the fine and dense particles of LPONP which are          Quite often at patients can form LPONP particles increased in sizes which cannot get into a wall of arteries and not an aterogenna are found. The specified features of a family gipertriglitseridemiya explain various risk degree of a prematurity of an ischemic heart disease at various patients. The xanthomatosis is not characteristic of a family gipertriglitseridemiya, but adjournment of lipids on edge of an iris of the eye can be observed.

Family deficit of a lipoprotein lipase

Family deficit of a lipoprotein lipase — the autosomal and recessive disease which is characterized by decrease of the activity or total absence of a lipoprotein lipase owing to what very high level of triglycerides in blood is observed. The disease meets seldom. Manifestation of family deficit of a lipoprotein lipase begins already at the earliest age and includes:
sudden pristua of abdominal pain, without accurate localization, but quite often surrounding character;
often recurrent pancreatitis with the expressed clinical symptomatology;
eruptive xanthomas;
hepatomegalia;
splenomegaly;
infiltration of bones foamy cells;
otlozheniyelipid in a retina (at sharply expressed triglitseridemiya);
high level of triglycerides in blood (> 8.5mmol/l);
giperlipoproteinemiya of I or V types;

As it was specified earlier, a hepatomegalia and a splenomegaly — characteristic symptoms of a disease. At insufficiency of a lipoprotein lipase capillaries of a liver and spleen are overloaded with chylomicrons, cells of reticuloendothelial system of these bodies begin to take intensively chylomicrons from blood, and it leads to increase in a liver and spleen.
Development of pancreatitis is caused by the fact that a pancreas a certain quantity of a lipase in capillaries along with secretion in a 12-perstny gut. Under the influence of a lipase in capillaries of a pancreas a large number of cleavage products           in particular, fatty acids which can be exposed to oxidation with allocation of the free radicals possessing cytotoxic and pro-inflammatory action is formed.

Family deficit of apoprotein C-II

Family deficit of apoprotein C-II — an autosomal and recessive disease which cornerstone decrease of the activity of a new lipase in connection with deficit of apoprotein C-II is. As it was specified earlier, apoprotein C-II is the activator of a lipoprotein lipase. Due to the functional deficit of a lipoprotein lipase hydrolysis is sharply broken       and          the symptomatology of family deficit of apoprotein C-II is similar to manifestations of family deficit of a lipoprotein lipase: recurrent pancreatitis,           eruptive the high level of triglycerides in blood (> by means of a method of a cut absence or sharply expressed deficit of apoprotein C-II comes to light. At heterozygous patients the content of apoprotein C-II in blood is reduced less considerably (only and the clinic of a disease is less expressed, and in certain cases can be absent, but the level of triglycerides in blood is moderately reduced.
The electrophoresis of lipoproteins in polyacrylamide gel reveals I or V types of a gaperlipoproteinemiya at family deficit of apoprotein C-II.

The family combined lipidemia

The family combined lipidemia — the inborn autosomal and dominant disease which is characterized by the expressed polymorphism of a lipidic range at patients and their close relatives. The exact nature of genetic defect is not known. Existence of mutations or polymorphism in the field of the genes coding synthesis of a lipoprotein and A-I, C-III, A apoproteins - IV is supposed. There is also a point of view that apoprotein hyperproduction   the Approximate frequency of a disease — 1 case on 100 people is the cornerstone of a disease.
A variety of disturbances of a lipidic exchange is characteristic, at one patients IIA giperlipoproteinemiya type with isolated at others — type with contents increase comes to light
in blood of cholesterol and triglycerides, at many patients the giperlipoproteinemiya of the IV type with the isolated gipertriglitseridemiya develops. The same polymorphism is characteristic also of relatives of patients, i.e. in the same family various types of a giperlipoproteinemiya are observed. The type of a gaperlipoproteinemiya can change during the patient's life
Content of cholesterol in blood of patients fluctuates from 6.5 to 13 mmol/l, and the level of triglycerides — from 2.8 to 8.5 mmol/l.
The disease contributes to an ischemic heart disease prematurity; differs from a family hypercholesterolemia in lack of a xanthomatosis of sinews.

Disbetalipoproteinemiya

Family disbetalipoproteinemiya (remnantny giperlipoproteinemiya, giperlipoproteinemiya of the III type) — the rare genetic disease which is transmitted in the autosomal and recessive way, characterized by a giperlipoproteinemiya of the III type, caused by disturbance of a catabolism of chylomicrons and LPONP. The disease meets frequency of 1 a case on the 5000th population. The mutation of the gene controlling apoprotein E synthesis that leads to emergence of a mutant form apo E is the cornerstone of a disease (apo E2). It is known that apoprotein E causes binding of the remnantny (residual) particles which are formed at a catabolism of chylomicrons and LPONP with apo V/E and apo E-retsepto-ramy a liver. The normal phenotype apo E is apo EZ.
The mutant form apo E (apo E2) poorly interacts with the specified receptors owing to what extraction from blood of remnantny particles decreases, their level increases in blood that leads to substantial increase in blood of content of cholesterol (usually within 6.5 — 13.0 mmol/l) and triglycerides (2.8 — 5.6 mmol/l).
The Remnantny particles collecting at this disease in blood are characterized at an electrophoresis by bigger mobility, than usual LPONP, and received the name R-LPONP. As a rule, the disease is shown at adults, development of clinical symptomatology is often promoted by an alcohol abuse, a diabetes mellitus, obesity, a hypothyroidism.
Main manifestations of a disbetalipoproteinemiya:
Linear xanthomatosis of folds of palms and fingers, emergence of hilly xanthomas of other localization (in various body parts); rasprostranennyyaterosklerotichesky process with defeat of coronary arteries (that leads to development of an ischemic heart disease), carotid, renal arteries and arteries of the lower extremities;
gipertriglitseridemiya igiperkholesterinemiya;
giperlipoproteinemiya of the III type with the increased quantity in LPPP blood and normal quantity of LPNP; on an elektroforegramma of blood serum the wide r-strip (from here the second name — an illness of "a wide strip") is defined which is caused by surplus of LPPP and remnant of chylomicrons;
apoprotein E vyyavleniyeizoforma — apo E2;
size of relation HSLPONP / plasma triglycerides> 0.3.

Other types of primary dislipidemiya

Primary gipoaljfalipoproteinemiya — the disturbance of an exchange of lipoproteins which is characterized by decrease in concentration of the XC LPVP and, therefore, low content in blood of alphalipoproteins (LPVP). The disease is caused by mutations of the gene coding A-I apoprotein synthesis. This gene is localized in a chromosome 11. Besides, can it is caused by hereditary deficit of enzyme of a letsitinkholesterinatsiltransferaza (about a role of this enzyme in synthesis and - lipoproteins or LPVP see in the section "Lipoproteins of High Density"), Deficit of LPVP promotes a prematurity of atherosclerosis of arteries and an ischemic heart disease. It is possible to speak about deficit of LPVP if the content of LPVP cholesterol in blood at men is lower than 0.9 mmol/l, women have lower than 1.2 mmol/l. It is possible to find the LPVP low level also in the analysis of results of an elektroforegramma of lipoproteins of blood.
Family giperalfalipoproteinemiya — the inborn disturbance of an exchange of lipoproteins which is characterized by increase of content in LPVP blood (alpha lipoproteins).

Distinguish two pathogenetic kinds of a disease. One form is characterized by activation of synthesis of A-I apoprotein and, respectively, LPVP. At this form of a giperalfalipoproteinemiya no clinical pathological symptoms come to light. It is established that at this form of a giperalfalipoproteinemiya life expectancy (perhaps considerably increases because does not develop     therefore the first option of a giperalfalipoproteinemiya is called still a longevity syndrome.
The second kind of a family giperalfalipoproteinemiya is caused by hereditary deficit of protein, the transferring        cholesterol (its role is shown in fig. 5), at the same time most the Increase in Content in LPVP Blood fraction considerably increases at deficit of the protein transferring cholesterol ethers it is caused also by delay of speed of a catabolism of A-I and A-II apoproteins. This type of a family giperalfalipoproteinemiya is followed by the high level of triglycerides in blood, decrease in content of cholesterol in fractions of LPONP, LPPP and LPNP.

The diagnosis of a family giperalfalipoproteinemiya is made on the basis of determination of low content in LPVP cholesterol blood, and also reduction of maintenance of the LPVP most fraction at an electrophoresis of lipoproteins of blood with the subsequent to it their fractions.
The most often found primary (hereditary) giperlipoproteinemiya are:
family gaperkholesterinemiya (most often heterozygous form);

It is possible to suspect existence of a hereditary giperlipoproteinemiya on the basis of the following signs:
the postponed myocardial infarction at persons of young age (especially at women);
existence of signs of atherosclerotic damage of arteries of various localization at young faces;
the instruction in the anamnesis on development of an ischemic heart disease in the immediate family at young age.
It is recommended to conduct careful research of the main indicators of a metabolism of lipoproteins at the persons having the above-stated signs of predisposition to primary giperlipoproteinemiya.
Other rare options of genetically caused disturbances of a metabolism of lipids are provided to tab. 3.
Tab. 3. Rare genetic disorders of a metabolism of lipids (Ginsberg, Goldberg, 1998)