LIPIDOSES (lipidosis; a lipid(s) + - osis; ustar. lipoidoses) — group of the diseases which are characterized by disturbance of lipidic exchange and having in most cases hereditary character. Reason of hereditary (primary) L. more often there is a genetic defect of any enzyme. Majority of L. is diseases of accumulation (see. Tezaurismoza ), since as a result of insufficiency of the certain enzyme participating in lipid metabolism (see. Lipometabolism ) or lipoproteids (see), in cells or biol, liquids of an organism find abnormally large amounts of not split substrate of the corresponding enzyme. Classification is finally not developed, origins of L. continue to be studied.
Big group L. — glycolipidoses (see. Glikozidoza ), i.e. diseases of which pathogeny disturbance of disintegration of a carbohydrate component is the cornerstone glycolipids (see). The most widespread glycolipids in a human body — sfingoglikolipida therefore the diseases connected with disturbance of exchange of a carbohydrate part of their molecules carry the independent name «sfingoglikolipidoza». Thus, the terms «glycolipidoses» and «sfingoglikolipidoza» are close. However, strictly speaking, these terms are not synonyms of the term «sphingolipidoses» which is widely used in literature combining wider group of hereditary diseases with disturbance of exchange (generally disintegration) not only a carbohydrate, but also lipidic component of lipids of this class. In spite of the fact that the majority of the known sphingolipidoses represents sfingoglikolipidoza, diseases at which lack of the enzymes catalyzing disintegration of a lipidic component of sfingoglikolipid is genetically caused concern to the same group of diseases (e.g., at Farber's disease there is no enzyme of a tseramidaz) or the remains of not carbohydrate nature catalyzing eliminating, such as phosphosincaline (e.g., a sphingomyelinase at Nimann's disease — Peak) or sulfate (e.g., arylsulphatase A at a metachromatic leukodystrophy).
Hereditarily the caused disturbance of exchange of gangliosides (glycolipids which carbohydrate part of a molecule contains the rest of sialic acid) is the reason of gangliozidoz. The disease Teja belongs to gangliozidoza — the Saxophone (GM2 ганглиозидоз, type I), in a brain of patients with this disease significant amounts of Om2-gangliozida for lack of a geksozaminidaza collect And, for a cut the Gm2-ganglioside is substrate (see. Amaurotic idiocy ). At so-called zero option of a disease Teja — the Saxophone — Sandgoff's diseases (to Gm2-gangliozidoza II of type) in tissues of patients are absent activities geksozaminidaz And yes to V. Kroma of Sandgoff's disease, distinguish youthful GM2 ганглиозидоз the III type, or Berngeymer's disease — Zaytelbergera who is characterized by reduction of activity of a geksozaminidaza And, and infantile (children's) GM2 ганглиозидоз, the option of AV, at Krom activity geksozaminidaz And yes In does not change, but there is no specific thermolabile factor necessary for splitting of a Gm2-ganglioside geksozaminidazy And. This type GM2 ганглиозидоза can be revealed only if as substrate the natural GM2 ganglioside since the specific proteinaceous factor of influence does not render on splitting of synthetic substrate is used. Treat the partial gangliozidoza connected with disturbance of disintegration of GM1-ganglio-zida generalized GM1 ганглиозидоз, or Norman's disease — Landinga (there are no beta galactosidases And, In and C), and youthful GM1 ганглиозидоз, or a disease of Derry (activity In - and S-forms of a beta galactosidase is considerably reduced).
There are data on new type of a glycolipidosis — GM3 ганглиозидозе, development to-rogo is connected not with accumulation of not split gangliosides, i.e. with genetically caused block of their catabolism, and with disturbance of their biosynthesis. Accumulation in a liver and a brain of patients with this disease of a GM3 ganglioside results from lack of the specific N-atsetilgalaktozaminiltransferazy catalyzing transformation of a GM3 ganglioside into a GM2 ganglioside.
Fabri's disease — only among glycolipidoses, at a cut genetic defect is definitely connected with X-chromosome; it is caused by deficit of activity tseramidtrigeksozid - alpha galactosidases And (see. Fabri disease ). At Fabri's disease in tissues of patients, and also in their leukocytes and fibroblasts a large number of a tseramidtrigeksozid who is removed with urine collects.
One of very widespread glycolipidoses — a disease to Gosha (see. to Gosha disease ). A key product of accumulation at it is tseramidglyukozid (glyukotserebrebrozid) — not split substrate of the reaction catalyzed by acid beta glucosidase (glyukotserebrozidazy) which collects in reticuloendothelial cells. Activity of acid beta glucosidase (see. Glucosidases ) at this disease decreases in different degree depending on a form of a disease up to total absence. For the most severe infantile form of a disease residual activity of a glyukotserebrozidaza makes less than 9% of activity of enzyme normal. The youthful form of a disease is characterized by 10 — 17% of residual activity of a glyukotserebrozidaza, and an adult form — even 40% of activity of enzyme. Existence of various forms of a disease to Gosha is caused, apparently, by various mutations in same (or similar) the genetic locus controlling formation of a glyukotserebrozidaza.
At the heart of a pathogeny of a globoidnokletochny leukodystrophy (Krabbe's disease) and a family metachromatic leukodystrophy of Greenfield — Sholtsa (see. Leukodystrophy ) genetically determined deficit of a beta galactosidase (tseramidgalaktozidaza) and tserebrozidsulfataza (arylsulphatase A) lies. At Krabbe's disease a product of accumulation is tseramidgalaktozid (galaktotserebrozid), and at a family metachromatic leukodystrophy in nervous cells, nerve fibrils, in a glia of c. N of page, and also in a retina of eyes, tubules of nights and leukocytes collect cerebroside sulfatides.
On a clinical picture to Krabbe's disease it is similar mukolipidoz, however at it the volume of internals does not increase and the amount of mucopolysaccharides in urine remains normal.
At genetically caused defect of a sphingomyelinase in retikulomakrofagalny system and a brain, and also in mesenchymal and epithelial elements of many bodies a large amount of sphingomyelin collects. In marrow there are multinuclear macrophages — cells of Peak (see. Nimanna-Pika disease ).
In 1888 the American neuropathologist and the psychiatrist F. X. Dercum for the first time described a neuroendocrinal disease, education under skin of multiple painful lipomas was characteristic manifestation to-rogo. Assume that this disease has hereditary character since it was observed at several members of one family (see. Derkuma disease ).
At genetic defect of steapsin ability to completely digest fats is lost. Apprx. 50 — 80% of the fats arriving with food it is allocated with a stake which differs in an oily consistence. Insufficiency of an acid lipase is an etiology of Volman, at a cut in internals the «foamy» cells containing a large amount of triglycerides and cholesterol are found. The disease is characterized by calcification of adrenal glands, a gepatosplenomegaliya and xanthomatosis (see), i.e. adjournment in skin and some fabrics of cholesterol and triglycerides, shown education xanthomas (see).
The xanthomatosis accompanies also the lipoproteinemiya of the I type [according to D. S. Fredrickson] developing owing to genetic defect lipoproteidlipaza (see). The hereditary aalfalipoproteinemiya — the Tangier disease — is characterized by absence in blood of normal lipoproteids of the high density (α-lipoproteids)))))))))) and emergence of abnormal lipoproteids of high density (see. Lipoproteids ).
Other hereditary pathology of this kind — abetalipoproteinemiya (see) it is characterized by absence in blood not only beta lipoproteids, but also pre - beta lipoiroteidov and chylomicrons. In this case the main metabolic defect is connected with oppression of synthesis of protein apo-V in a liver. This protein is necessary for formation of the listed lipoproteids. The hereditary disease caused by insufficiency lecithin is known: cholesterol — acyltransferases (so-called. LHAT-insufficiency). This enzyme catalyzes etherification of cholesterol. As a result of disturbance of etherification of cholesterol the structure and morphology of lipoproteids of a blood plasma change. Adjournment of not esterified cholesterol in a spleen, kidneys, a cornea, an erythrocyte membrane is characteristic of this disease. Its clinical manifestations — hypochromia anemia, a renal failure, a splenomegaly, opacification of a cornea etc. Besides, in blood appear abnormal lipoproteids - X.
The acquired (secondary) L. are usually connected with disturbance of exchange of cholesterol. The diseases of the tumoral nature which received the name concern to them histiocytoses (see), and also secondary giperkholesterinemichesky xanthomatosis and secondary giperlipemichesky xanthomatosis. Enter into group of histiocytoses the acute system progressing histiocytosis (Letterer's disease — Siwa), hron, the system progressing histiocytosis (Hend's disease — Schueller — Krischena) and an eosinophilic granuloma. Disease Henda — Schueller — Krischena reminds some sphingolipidoses. In a basis patol, process at this disease disturbance of exchange of cholesterol lies. A wedge, its manifestation — a xanthomatosis with dystrophy of the bone tissue and internals caused by adjournment of cholesterol and its ethers, triglycerides and phosphatides in the proliferating histiocytes taking a foamy form and turning in multinuclear huge macrophages.
Local manifestation of a row patol, processes and diseases are secondary local L., which can be connected with destruction of the fabrics rich with lipids, with formation of abnormal quantities of lipids at these or those patol, processes, with local frustration krovo-and lymphokineses, with an inflammation or development of a tumor. Morfol, signs of such L. are formation of lipophages and lipogranulomas, liposklerotichesky (atherosclerotic) plaques p atheromas, lipoid infiltration as again formed substances (a hyalin, amyloid), and fabrics at an inflammation, reparative regeneration or a tumor. The greatest distribution among secondary local L. has atherosclerosis (see).
An experimental vascular lipidosis
On separate morfol, and tsitol, to signs to L. the so-called experimental vascular L can be carried., at Krom exchange of cholesterol and lipoproteids is broken; the mechanism of these disturbances is not found out. Experimental vascular L. on a nek-eye to data represents an initial stage of atherosclerosis.
Experimental vascular L. it can be received as a result of feeding by an animal of large amounts of cholesterol, saturated fat, and also after the repeated intravenous administration by an animal of homologous lipoproteids of low and very low density offered by A. N. Klimov and soavt. (1967). Most often for this purpose use rabbits, pigs of tiny breed and monkeys; in the course of the experiment their increase is noted in a blood plasma of concentration of lipoproteids of low and very low density.
Morphologically experimental vascular lipidosis first of all is shown in formation of small lipidic spots and strips of yellowish color. In spots and strips the content of cholesterol, to a lesser extent phospholipids and triglycerides is sharply increased.
The sequence of the changes happening in a vascular wall is represented as follows. In the beginning changes of permeability of an endothelial barrier are shown. In response to increase in level beta and pre - beta lipoiroteidov in blood pinotsitozny activity of endothelial cells increases. Along with it there are changes on a surface of endothelial cells — a loosening and disappearance of a protective carbohydrate layer (glycocalyx). Increase in pinotsitozny activity is followed by partial or full disclosure of interendothelial spaces that allows to get and be postponed freely in an internal cover of arteries to lipoproteids and other proteins of a blood plasma. It is promoted by education in a vascular wall physical. - a chemical complex beta and pre - beta lipoproteids and glikozaminoglikan of the main substance of its internal cover. Filling with lipidic vacuoles of cytoplasm of endothelial cells, their reduction or stretching with the bulking-up interstitial fabric causes death of separate endothelial cells.
At this stage macroscopically lipidic spots are not visible yet, and diffusion adjournment of lipids only in the main substance is microscopically observed.
In response to receipt in a subendothelial layer of lipoproteids reaction from the main substance and cells producing it is noted: the quantity of acid glikozaminoglikan increases, formation of collagenic and elastic fibers amplifies. Cellular reaction is expressed first of all in the strengthened proliferation of smooth muscle cells. Smooth muscle cells of a subintimalny layer of an average cover of an artery (miointimalny foamy cells) get into an internal cover through the loosened inner elastic membrane and take part in absorption of lipoproteids and lipids.
An important point of metabolism of lipids in cytoplasm of foamy cells is the contact and alloyage of lipidic vacuoles with primary lysosomes (see) thanks to what secondary lysosomes are formed. A part of hydrolysates of lipoproteids (fat to - you, amino acids, etc.) by diffusion through a membrane of a secondary lysosome come to cytoplasm of a cell where are used or for power needs, or for synthesis of new macromolecules. Free not esterified cholesterol collects in cytoplasm of cells, is frequent in the form of the crystals surrounded with the condensed cytoplasm. Ethers of cholesterol because of their bigger water repellency create intracellular drops like triglycerides. Sharply reduced activity of holesterinesterazny enzymes in cytoplasm of cells leads to excess accumulation of cholesterol in cells and an arterial wall in general.
During the progressing of L. death of the cells overloaded with lipids can take place. An exit of hydrolases in intercellular space causes a necrosis of surrounding fabrics and promotes the strengthened proliferation of connecting fabric. Same decrease of the activity of oxidation-reduction enzymes in a vascular wall accompanies. Thus transition of L is obviously possible. in a mode of formation of atherosclerotic plaques.
At short-term feeding of animals cholesterol at a stage of experimental vascular L. processes of regression of the lipidic centers can take place.
Bibliography: Davidenkova E. F. and Liberman I. S. Klinicheskaya of the geneticist, page 285, L., 1975; Makkyyusik V. A. Ancestral features of the person, the lane with English, M., 1976: Harris G. Fundamentals of biochemical genetics of the person, the lane with English, M., 1978, bibliogr.; S r of a n g e r J. W. a. W i e e clin a n n H. R. The genetic mucolipidoses, diagnosis and differential diagnosis, Hum. Genet., v. 9. p. 113, 1970; Stanbu-r at J. B., W y n g an a r d e n J. B. a. Fredrick s o n D. S. The metabolic basis of inherited disease, N. Y. a. o., 1972.
B. B. Sirs, H. G. Budkovskaya; And. H. Klimov, B. A. Nagornev (experimental lipidosis).