PEROXIZÓMOVÉ DEDIČNÉ METABOLICKÉ CHOROBY

Peroxisomal Hereditary Metabolic Disorders

Metabolic function of peroxisomes includes oxidation of wide spectrum of substances in the presence of oxygen.Hydrogen peroxide formed at the same time is either degraded by catalase or further utilized in peroxidative reactions.From the view of cellular pathology, the most important becomes alpha and beta-oxidation of carboxylic acids,particularly beta-oxidation of long-chain carboxylic acids, which undergoes selectively in peroxisomes. Mutationsof peroxisomal genes result in serious metabolic disorders. At present about twenty hereditary peroxisomal diseaseshas been described. One group of them includes generalized forms (impairment of peroxisome biogenesis); diseasesof other group result from isolated defects of individual peroxisomal enzymes. Combined incidence of peroxisomalhereditary disorders in the Western Europe is estimated to be 1:10 000. Beside the X-linked adrenoleukodystrophy,all others have the autosomal-recessive type of heredity. In phenotypic manifestation of generalized forms, as in theZellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, rhizomelic chondrodysplasia pun-ctata, an impairment of the central nervous system, liver, and kidney dominate. Most of the patients die within oneyear, survival period longer than three years becomes exceptional. X-adrenoleukodystrophy, pseudoneonataladrenoleukodystrophy, trifunctional enzyme deficiency, Refsum disease, primary hyperoxaluria, acatalasemia resultfrom the deficiency of a single enzyme. The most frequent peroxiosomal hereditary disease, the X-adrenoleukodys-trophy, has several clinical phenotypes, which most frequently manifest already in infants. The disease has alsoa clinically less serious form, which manifest only in adults – the adrenomyeloneuropathy. For the postnatal but alsofor the prenatal diagnostics, methods of biochemistry, molecular genetics, morphology, and immunocytochemistryare necessary.

Key words:
peroxisomes, beta-oxidation, metabolic functions of peroxisomes, peroxisomal hereditary disorders,Zellweger syndrome, adrenoleukodystrophy, Refsum disease.