Diagnostic and pathogenetic investigations of
peroxisomal disorders should include the study of the macroscopic and microscopic pathology of the liver, in addition to careful clinical observations, skeletal X-ray and brain CT scan, assays of very long-chain
fatty acids and
bile acid intermediates, and selected
enzyme activities. This review of the literature also contains novel observations about the following syndromes: cerebro-hepato-renal (
Zellweger) syndrome, X-linked and
neonatal adrenoleukodystrophies (ALD, NALD), NALD-like syndromes, infantile
phytanic acid storage, classical
Refsum disease, rhizomelic and other forms of
chondrodysplasia punctata (XD, XR, AR), hyperpipecolic acidaemia,
primary hyperoxaluria I, pseudo-Zellweger and Zellweger-like syndromes, and single
enzyme deficiencies. Microscopic data include
catalase staining and morphometry of peroxisomes, immunolocalization of beta-oxidation
enzymes, detection of trilamellar, polarizing inclusions in PAS-positive macrophages,
fibrosis and
iron storage. Peroxisomal enlargement appears to be related to functional deficit in beta-oxidation disorders as well as in
rhizomelic chondrodysplasia punctata. Because normal peroxisomal localization of active beta-oxidation
enzymes can accompany a C26 beta-oxidation deficit, other mechanisms such as impaired transport of metabolites should be investigated. 'Ghost'-like organelles are shown in the liver of an infantile Refsum patient and in an NALD-like case; immuno-
gold labelling of
membrane proteins did not reveal ghosts in Zellweger livers.