Diseases associated with impaired connective tissue exchange

Three main components of connective tissue are distinguished:

■ cellular elements;

■ collagen, elastic and reticular fibers;

■ amorphous basic substance.

Genetic defects in the synthesis and breakdown of various structural components of connective tissue lead to the development of hereditary

diseases. Among the diseases in which collagen and elastic fibers are affected, Marfan's disease is most often observed. A group of diseases, which are based on a violation of the metabolism of an amorphous substance, mainly acidic glycosaminoglycans, are called mucopolysaccharidosis.

Marfan disease is a hereditary disease characterized by a systemic lesion of connective tissue. In the development of the disease, the defeat of collagen and elastin is important, manifested in the violation of intra- and intermolecular bonds in these structures. The primary genetic defect that causes Marfan's disease is associated with damage to the fibrillin-1 gene( # 154700, 15q15-q21.3, FBN1 gene [* 134797], Normally this gene codes for synthesis of connective tissue protein - fibrillin-1( structural glycoprotein component of elastin) The patients are characterized by high growth, long( spidery) fingers, femoral and inguinal hernia, hypoplasia of muscles and subcutaneous tissue, flat feet, heart defects, aortic aneurysm

Mucopolysaccharidosis The most important part of the connective tissue is proteoglycansmolecules consisting of a fibrous central protein with covalently attached glycosyl-minoglycans.) The number and ratio of different proteoglycans depends on the type of connective tissue they form in fibroblasts. In lysosomes of the same cells, proteoglycans after endocytosis are destroyed. The destruction of glycosaminoglycans begins with a terminal monosaccharide underthe action of specific lysosomal glycosidases If any lysosomal enzymes are absent( genetic defect in their synthesis) or their activityand in the connective tissue of various organs, the accumulation of undisturbed or partially destroyed proteoglycans begins. Therefore, mucopolysaccharidosis refers to accumulation diseases.

Currently, there are 9 major types of mucopolysaccharidosis, characterized by deficiency of various enzymes and certain features of the clinical picture. The list of main types of mucopolysaccharidosis, defective enzymes, chromosomal gene localization, types and number of mutations are given in the table.

Table Molecular-genetic bases of mucopolysaccharidoses

Table Molecular-genetic bases of mucopolysaccharidosis