Infantile Refsum disease.

Disorders attributable to peroxisomal dysfunction are well recognized on the basis of their clinical and biochemical characteristics. These observations have resulted in a preliminary classification that recognizes two major groups of disorders, both of which are genetically determined. Group 1 consists of the generalized peroxisomal disorders that frequently cause signs and symptoms in the newborn period , are inherited in an autosomal recessive manner, and result from a failure of the peroxisomes to form or maintain themselves so that functional defects are present in more than one enzyme of this organelle. It is to this category that infantile Refsum disease (IRD) belongs [1 , 2]. Other members of this group include Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and hyperpipecolic acidemia. Group 2 consists of a growing number of disorders in which the peroxisomes are normal in appearance, and only one enzyme defect occurs. This class includes X-linked adrenoleukodystrophy, hyperoxaluria type 1 , acatalasia, acyi-CoA oxidase deficiency, bifunctional enzyme deficiency, and pseudo-Zellweger syndrome-thiolase deficiency. A third group, in which peroxisomes are present, but multiple enzyme defects occur, is exemplified by rhizomelic chondrodysplasia punctata (RCDP), but the position of this disorder in the classification is uncertain. Several recent reviews [3-5) provide further details of the distinguishing biochemical features of peroxisomal disorders. Attention to the peroxisome as a cause of disease in humans stems from the observation that these organelles are completely absent in Zellweger syndrome; this was attributed to defective formation of the membrane [6) . More recent studies [3, 7] have shown that the primary defect involves