What are peroxisomal disorders?
Peroxisomal disorders are rare congenital diseases characterized by the absence of peroxisomes in the cells of the body . Since peroxisomes cannot be formed and all peroxisomal functions are defective, they are called disorders of peroxisomal biogenesis or generalized peroxisomal disorders . Peroxisomes are small cell particles that carry out important biochemical reactions, most of them related to fat metabolism. These reactions are “promoted” by enzymes, which are specialized proteins that catalize or facilitate biochemical reactions by increasing their speed. Without enzymes, reactions would be so slow that they would be totally ineffective. If peroxisomes are absent or not functioning, reactions normally catalized by peroxisomal enzymes are defective. This is what happens in Zellweger’s syndrome, the prototype of generalized peroxisomal disorders.
One of the most characteristic reactions that take place in the peroxisome is the breaking down (by b-oxidation) of very long chain fatty acids (VLCFA) with more than 22 carbon atoms (typically 24 and 26 carbon atoms). Peroxisomal b-oxidation shortens the chain length of the fatty acids until they can be further broken down in the mitochondria. If peroxisomes are absent this process is defective and the VLCFA increase in plasma and tissues. This is one of the hallmarks for the diagnosis of peroxisomal disease. Other characteristic abnormality is the decrease in plasmalogen levels. Plasmalogens are a special kind of phospholipids mainly localized in myelin (the fatty material that covers nerve fibers and forms white matter in the brain). Other typical lipid abnormalities are the increases in phytanic acid and in its a-oxidation product pristanic acid. Cholesterol and bile acid synthesis are also affected, which results in the low levels of these lipids found in peroxisomal diseases. Since their synthesis is blocked, some bile acid intermediates DHCA (dihydroxycholestenoic acid) and THCA (trihydroxycholestanoic acid) appear in blood and urine.