Peroxisomal Defects: Refsum Disease and Adrenomyeloneuropathy

Abstract Peroxisomes are single-membrane-bound organelles, measuring about 0.2 to 0.5 µm in diameter. They lack DNA and have no defined internal cytoarchitecture. These organelles are found in all cells in the human body, especially the liver and kidney, but are absent from mature erythrocytes.1 Peroxisomes catalyze the 13 oxidation of fatty acids and related substrates. Those preferentially or exclusively oxidized in peroxisomes include very long chain fatty acids (VLCFA), polyunsaturated fatty acids, dicarboxylic fatty acids, prostaglandins, and the side chain of cholesterol. Peroxisomes also catalyze the initial reaction in the biosynthesis of plasmalogens, which are phospholipids abundantly found in the myelin. Bile acid formation requires peroxisomes and they are the principal site for H202-based cellular respiration using catalase and oxidases. Peroxisomal disorders can be divided into two major categories: those in which peroxisomes are absent or severely reduced because their assembly is defective, and disorders involving single peroxisomal enzyme defects. The peroxisomal disorders associated with neurological dysfunction are listed in Table 24-1. Peripheral neuropathy occurs as a predominant manifestation of two peroxisomal disorders, both caused by single enzyme defects: Refsum disease (Table 24-2) and X-linked adrenomyeloneuropathy (a subtype of adrenoleukodystrophy) (see Table 24-3). These disorders are genetically distinct from other conditions that carry similar names: neonatal adrenoleukodystrophy and infantile Refsum disease.