Six patients with disorders of peroxisomal function have been studied. Two presented in the neonatal period with the classical features of the
Zellweger syndrome, two had incomplete Zellweger phenotypes, one
infantile Refsum's disease and one
rhizomelic chondrodysplasia punctata. Plasma
bile acid profiles were determined using capillary gas chromatography-mass spectrometry. In all patients, except the case of
chondrodysplasia punctata, 27-carbon and 29-carbon
bile acids were present. The compounds identified included trihydroxycoprostanic
acid (THCA), dihydroxycoprostanic
acid (DHCA), C24-, C25- and C26-hydroxylated derivatives of THCA, a 27-carbon
acid with four nuclear hydroxy groups and 3 alpha,7 alpha,12 alpha-trihydroxy-27a,27b-dihomo-5 beta-cholestan-26, 27b-dioic
acid (C29-dicarboxylic acid). THCA was present at a low concentration in the patient with
infantile Refsum's disease; the concentration of DHCA and the C29 dicarboxylic
acid were considerably higher. The presence of abnormal
bile acids in patients with
Zellweger syndrome and
infantile Refsum's disease could be explained by the absence of peroxisomes from their hepatocytes. In
chondrodysplasia punctata the cause of peroxisomal dysfunction must be different, since normal
bile acid synthesis is preserved.