PubMed1988
The history of the peroxisomal disorders (PDs), including the most frequent variant, the cerebrohepatorenal syndrome of Zellweger, can be divided into four phases. During the first phase, lasting from 1964 to 1972, the clinical and pathologic manifestations of Zellweger's syndrome (ZS) were explored and delineated. In 1973 it was found that ZS is due to the absence of peroxisomes in hepatocytes and renal tubular epithelial cells. With this discovery the second phase of ZS was initiated, which in subsequent years led to discovery of various defective peroxisomal functions. During the third phase, beginning in 1980, various other peroxisomal disorders were discovered, among them infantile Refsum's disease, hyperpipecolic acidemia, neonatal adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata. During 1986 the etiology of the various PDs was identified by complementation studies, marking the beginning of the fourth phase of the history of the peroxisomopathies. It was found that ZS, neonatal adrenoleukodystrophy, and rhizomelic chondrodysplasia punctata represent different genetic entities, while Refsum's disease and hyperpipecolic acidemia are alleviated variants of ZS. Moreover, results of preliminary studies indicate that cells of one case of ZS may complement the cells of another ZS case, which could indicate genetic heterogeneity of ZS.