ABSTRACT
The review summarizes the current literature data on the inherited metabolic disorder of branched-chain amino acids - methylmalonic aciduria, characterized by high mortality, acute onset and crisis course. The paper presents the molecular genetic characteristics of the known thirteen different genes (responsible for the synthesis of methylmalonyl-CoA mutase, methylmalonyl-CoA epimerase and vitamin B12 metabolism), mutations of which lead to the development of methylmalonic aciduria. The current knowledge about the potential role of organic acids and their derivatives in the development of metabolic decompensation, toxic damage to the nervous system and internal organs is presented. Early diagnosis by tandem mass spectrometry is extremely important, since timely treatment started (diet therapy, the use of hydroxycobalamin in the B12-dependent form) prevent an unfavorable outcome and allow a high degree of rehabilitation for children with this pathology. Moreover, the identification of the primary molecular genetic defect makes it possible to adjust the patient management tactics and to carry out further prenatal diagnosis of the pathology in subsequent pregnancies.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Methylmalonic Acid , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acid Metabolism, Inborn Errors/genetics , Child , Female , Humans , Methylmalonyl-CoA Mutase/genetics , Mutation , PregnancyABSTRACT
Purpose - to establish a relationship between the incidence and the prevalence of breast cancer and air emissions of pollutants in the Aktobe region of the Republic of Kazakhstan.A retrospective study of the database was carried out on the territory of the Aktobe region of Western Kazakhstan. The data were obtained from the Register of Oncological Diseases of the Aktobe Regional Cancer Center. Data on air emissions for 2014-2019 were obtained from the Annual Statistical Bulletin "Environmental statistics. On the state of protection of atmospheric air in Kazakhstan" of the Committee on Statistics of the Republic of Kazakhstan.Breast cancer ranks is first among the malignant oncological pathology of women in the Aktobe region in 2019 and is 20.5% (95% CI 19.6-21.4) of all cancer cases. The analysis shows that the incidence and prevalence of breast cancer in 2014-2019 continues to grow: incidents from 37.3 (2014) to 56.0 (2019) per 100,000 population, the growth rate is 8.3%; prevalence: from 274.0 (2014) to 344.8 (2019) per 100,000 population, the growth rate is 4.7%. Spearman's rank correlation analysis showed a strong direct relationship between benzene emissions and the incidence (r=0.8, p=0.027). A direct strong relationship was found between the prevalence of breast cancer and the amount of emissions into the atmosphere (r=0.8, p=0.027), carbon monoxide (r=0.9, p=0.037), nitrogen oxides (r=0.9, p=0.037), lead (r=0.8, p=0.021), hexavalent chromium (r=0.6, p=0.048), xylene (r=0.7, p=0.047), toluene (r=0.8, p=0.034), methanol (r=0.8, p=0.040), butyl acetate (r=0.7, p=0.046).The unfavorable environmental situation in the Aktobe region associated with the release of chemical pollutants and heavy metals can contribute to the development of cancer. The revealed correlation between the prevalence of breast cancer and the release of chemical elements into the atmosphere requires further study to determine risk factors for breast cancer in the region of Western Kazakhstan.
