Diseases associated with metabolic disorders
Wilson-Konovalov's disease( hepatolenticular degeneration) is a disease caused by a hereditary copper exchange defect( * 277900, 13q14.3-q21.1, ATP7B p-polypeptide mutation of Cu2 + -transporting ATPase; p).In patients with blood plasma, the concentration of the main copper-bearing protein - ceruloplasmin and, to a lesser extent, another protein participating in the metabolism of copper, - cytochromoxidase is sharply reduced. The main manifestations of the disease are liver lesions( cirrhosis with
followed by hepatic insufficiency) and CNS( stem and cerebellar disorders, extrapyramidal rigidity, hyperkinesia, psychiatric disorders).
The pathological gene has been fully identified, therefore it is possible to detect mutations in it both by direct and indirect methods. More than 30 mutations have been identified in the ATP7V gene. In the European population the most significant mutations are His1070Gln and Gly1267Lys, recorded in 28 and 10% of all mutant chromosomes, respectively [Thomas G. R. et al., 1995].
Menkes syndrome is a disease resulting from dysfunction of copper-containing enzymes( * 309400, Xq12-q13, defects of genes encoding ATP7A, MNK, MK, OHS, 300011, Xq12-q13, n recessive cation-ATPase ATPase).The concentration of copper in serum is sharply reduced. As a result of the violation of transport of copper, various changes occur in the connective tissue( degenerative changes in the walls of the vessels, a violation of the structure of the tubular bones), is affected by the central nervous system.
Primary hemochromatosis( * 235200, 6p21.3, HFE gene, p; association with HLA A3, B7, B14) is due to increased absorption of iron in the small intestine and its accumulation in tissues, followed by damage and organ failure. In the clinical and morphological characteristics of primary hemochromatosis, it is necessary to take into account the distinct staging of its course. Typically, the preclinical and clinical stages are distinguished. The average age of patients with preclinical stage is 29 years, and in the stage of detailed clinical manifestations 44-49 years.
From the biochemical parameters for the diagnosis of primary hemochroma-toza, the concentration of iron and ferritin in the blood serum, the degree of saturation of transferrin with iron is used. Already in the preclinical stage the disease is characterized by profound disturbances in the parameters of iron metabolism. In the stage of detailed clinical manifestations, the concentration of iron in serum reaches 35-56 μmol / l, ferritin - 500-1500 μg / l, and the degree of saturation of transferrin with iron - 62-129%.The increase in serum ferritin concentration to 200 μg / l and higher in women and 300 μg / l and higher in men, as well as an increase in the saturation ratio of iron transferrin by more than 60%, is considered the most informative. The first indicator correlates with the iron stores in the patients and with the clinical manifestation of the disease, the second is the most simple and reliable marker of homozygous carriage of the allele of the primary hemochromatosis. Direct diagnostics of primary hemochromatosis by DNA analysis methods is possible.