2 – Neurobiology of Peroxisomal Disorders

Peroxisomal disorders are divided into two major groups: those in which peroxisome biogenesis is defective and the peroxisomes are morphologically abnormal or absent, which has an adverse impact on numerous peroxisomal functions (Group 1); and those in which a single protein, almost invariably a matrix enzyme, is deficient and their peroxisomes usually are morphologically intact (Group 2). Group 1, the peroxisomal biogenesis disorders (PBDs), formerly called general or generalized peroxisomal diseases, includes Zellweger cerebrohepatorenal syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum's disease (IRD) or phytanic acid storage disease, and rhizomelic chondrodysplasia punctata (RCDP). The most common disease in Group 2 is X-linked adreno-leukodystrophy (XALD, ALD) and its adult variant adrenomyeloneuropathy (AMN). The peroxisomal disorders are heredofamilial diseases and, with the exception of adreno-leukodystrophy/adrenomyeloneuropathy (ALD/AMN), are transmitted in an autosomal-recessive pattern; ALD/AMN is X linked. Group 1 and Group 2 disorders have both shared and distinctive neuropathological features. Their shared neuropathological features include abnormalities of myelin, usually of the central nervous system (CNS) and particularly cerebral and post developmental neuronal or axonal degenerations. Biochemical abnormalities of fatty acids are prominent markers of peroxisomal disorders and, hence, would be expected to play dominant roles in their pathophysiologies and pathogeneses.