Accumulation and impaired in vivo metabolism of di- and trihydroxycholestanoic acid in two patients.
Two patients with a suspected peroxisomal disorder on the basis of neurological, craniofacial, hepatological and other abnormalities were studied. The phenotype of both girls was remarkably similar from birth until age 1.5 yr. Detailed studies in plasma revealed normal plasma very-long-chain fatty acids but the presence of di- and trihydroxycholestanoic acids and the C29-dicarboxylic bile acid, all known to occur in plasma from Zellweger patients. These results suggest an isolated defect in the peroxisomal beta-oxidation of the side chains of the cholestanoic acids. Activation of trihydroxycholestanoic acid and beta-oxidation of trihydroxycholestanoyl-CoA, measured in a liver biopsy, were normal, however, as was the peroxisomal beta-oxidation of palmitate. Although the molecular defect remains unknown, the results stress the importance of performing multiple analyses in any patient suspected to suffer from a peroxisomal disorder and indicate that screening for peroxisomal disorders based upon analysis of only plasma very long chain fatty acids with or without analysis of erythrocyte plasmalogen levels, may be inadequate.
Wanders
R J
RJ
Department of Clinical Biochemistry, University Hospital Amsterdam, The Netherlands.
Casteels
M
M
Mannaerts
G P
GP
van Roermund
C W
CW
Schutgens
R B
RB
Kozich
V
V
Zeman
J
J
Hyanek
J
J
D000015:Abnormalities, Multiple / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000214:Acyl Coenzyme A / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002478:Cells, Cultured; D002777:Cholestanols / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000378:metabolism; D004200:Diseases in Twins; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008830:Microbodies / Q000378:metabolism / Q000648:ultrastructure; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D010641:Phenotype; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D012867:Skin / Q000378:metabolism; D014429:Twins, Dizygotic; D015211:Zellweger Syndrome / Q000378:metabolism; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
C000986:3,7-dihydroxycholestan-26-oic acid; D000214:Acyl Coenzyme A; D001647:Bile Acids and Salts; D002777:Cholestanols; D003998:Dicarboxylic Acids; D005230:Fatty Acids, Nonesterified; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D010171:Palmitoyl Coenzyme A; C022069:3,7,12-trihydroxycholestan-26-oic acid; C074626:3,7,12-trihydroxycholestan-26-oyl-CoA; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase