RESUMO
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.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Ácido Metilmalônico , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , Criança , Feminino , Humanos , Metilmalonil-CoA Mutase/genética , Mutação , GravidezRESUMO
The review summarizes the current knowledge about inborn errors of fatty acid metabolism (disorders of carnitine transport and mitochondrial fatty acid oxidation), characterized by high mortality, predominant damage of the central nervous system, heart, liver and skeletal muscles. The article presents the main clinical genetic features of diseases this group. After the introduction of newborn screening using the tandem mass-spectrometry (MS/MS), early identification of fatty acid metabolism defects became possible. Using of MS/MS method is promising for mass newborn screening. Early identification and accordingly timely initiated treatment prevents unfavorable outcome. Moreover, a specified medical-genetic diagnosis allows further prenatal diagnosis of pathology in subsequent pregnancies.
Assuntos
Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos/genética , Erros Inatos do Metabolismo , Triagem Neonatal , Espectrometria de Massas em Tandem , Feminino , Humanos , Recém-Nascido , Mitocôndrias , Oxirredução , GravidezRESUMO
The review highlights the current knowledge about the potential role of glycosaminoglycans in the induction of inflammation and development of damage of the functional systems of the organs by mucopolysaccharides (MPS). Undegraded glycosaminoglycans are stimulants of secondary events in the form of complex pathogenetic cascades: accumulation of secondary substrates unrelated to the defective enzyme, abnormal composition of the membranes, disorders of intracellular vesicular transport, impairment of autophagy, change of intracellular signaling (aberrant activation of signaling pathways), abnormalities of calcium homeostasis, oxidative stress. Understanding of the cellular processes underlying the pathophysiology of MPS helps to address the limitations of the existing therapies and to identify new therapeutic targets, which potentially form additional and effective ways of the therapy of the patients with MPS.
