The cerebrohepatorenal (Zellweger) syndrome. Increased levels and impaired degradation of very-long-chain fatty acids and their use in prenatal diagnosis.
The cerebrohepatorenal (Zellweger) syndrome is a fatal autosomal recessive disorder manifested in the neonatal period by profound hypotonia, psychomotor retardation, dysmorphic features, and an enlarged liver. In this study we demonstrate fivefold or greater increases of very-long-chain fatty acid levels, particularly hexacosanoic acid (C26:0) and hexacosenoic acid (C26:1), in plasma and cultured skin fibroblasts from 20 patients. Similar findings in cultured amniocytes from 3 of 14 women in whom the fetus was at risk of the Zellweger syndrome permitted prenatal diagnosis. Oxidation of very-long-chain fatty acids, which normally takes place in the peroxisome, was impaired in homogenates of cultured skin fibroblasts and amniocytes. This observation extends the evidence that the Zellweger syndrome belongs to the newly formulated category of peroxisomal disorders. The pattern of excess very-long-chain fatty acids differs from that demonstrated previously in patients with childhood adrenoleukodystrophy. The study of very-long-chain fatty acids provides a convenient method for the early diagnosis and prenatal detection of the Zellweger syndrome.
D000015:Abnormalities, Multiple / Q000175:diagnosis*; D000326:Adrenoleukodystrophy / Q000175:diagnosis; D000649:Amniocentesis; D001927:Brain Diseases / Q000175:diagnosis*; D003937:Diagnosis, Differential; D005227:Fatty Acids / Q000032:analysis* / Q000097:blood; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000032:analysis; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000175:diagnosis*; D008107:Liver Diseases / Q000175:diagnosis*; D008297:Male; D008830:Microbodies / Q000378:metabolism; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D013577:Syndrome
D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; C040938:1-hexacosenoic acid; C017364:hexacosanoic acid