Inborn errors in metabolism of carbohydrates, amino acids and fatty acids

Urođene metaboličke bolesti velika su skupina genetičkih i biokemijskih poremećaja metabolizma koje se najčešće nasljeđuju prema Mendelovim zakonima nasljeđivanja, a uzrokovane su mutacijama gena koji kodiraju određene enzime ili transportere, što je izraženo u bolestima u metabolizmu ugljikohidrata, aminokiselina i masnih kiselina. Prva i najstarija opisana bolest pripada skupini poremećaja metabolizma aminokiselina, a to je alkaptonurija. S obzirom na patofiziologiju postoje tri skupine poremećaja, a to su poremećaji koji uzrokuju intoksikacije, poput galaktozemije, tirozinemije, homocistinurije i urina s mirisom javorovog sirupa. Zatim poremećaji koji uključuju metabolizam energije, kao što su poremećaji oksidacije masnih kiselina (nedostatak izrazito dugolančane i srednjolančane acil-CoA dehidrogenaze), transporta karnitina, von Gierkeova bolest (metabolizam glikogena) i nedostatak glukoza-6-fosfat dehidrogenaze (put pentoza fosfata). Treća skupina su poremećaji složenih molekula u koje spadaju poremećaji staničnih organela. Navedene bolesti unutar prve i druge skupine nasljeđuju se autosomalno recesivno, osim nedostatka glukoza-6-fosfat dehidrogenaze koji se nasljeđuje X-vezano recesivno. Za dijagnosticiranje urođenih bolesti metabolizma, kao što je to kod poremećaja u metabolizmu makronutrijenata, koriste se različiti biomarkeri, a to su najčešće metaboliti koji se nakupljaju zbog blokade određenog metaboličkog puta uslijed nedostatka enzima ili transportera. Ovisno o dijagnozi, kliničkim znakovima i obliku bolesti osigurava se adekvatna nutritivna potpora.Inborn errors of metabolism are a large group of genetic and biochemical metabolic disorders that are frequently inherited according to Mendel's laws of inheritance, and are caused by mutations in genes encoding certain enzymes or transporters, what is expressed in diseases in the metabolism of carbohydrates, amino acids and fatty acids. The first and the oldest described disease belongs to the group of disorders of amino acid metabolism, and that is alcaptonuria. Considering pathophysiology, there are three groups of disorders, and these are disorders that cause intoxications, such as galactosemia, tyrosinemia, homocystinuria and maple syrup urine disease. Then there are disorders that include energy metabolism, such as disorders of fatty acid oxidation (very-long-chain and medium-chain acyl-CoA dehydrogenase deficiency), carnitine transport, von Gierke disease (glycogen metabolism) and glucose-6-phosphate deficiency (pentose phosphate pathway). The third group are disorders of complex molecules, which include disorders of cellular organelles. Diseases mentioned within the first and the second group are autosomal recessive according to inheritance, except the glucose-6-phosphate dehydrogenase deficiency which is X-linked recessive. To diagnose inborn errors of metabolism, such as disorders in macronutrient metabolism, various biomarkers are used, and these are most commonly metabolites that accumulate due to blockade of a particular metabolic pathway because of deficiency of enzymes or transporters. Depending on the diagnosis, clinical signs and form of the disease, adequate nutritional support is provided