Abstract | BACKGROUND & AIMS: METHODS:
Bile acids were measured by mass spectrometry in urine, bile, serum, and feces of the patient and in urine from the unrelated recipient. RESULTS: Liver biopsy specimens showed neonatal hepatitis with giant cell transformation and hepatocyte necrosis; peroxisomes were reduced in number. High concentrations of (25R)3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid in the urine, bile, and serum established a pattern similar to that of Zellweger syndrome and identical to the Alligator mississippiensis. Serum phytanic acid was normal, whereas pristanic acid was markedly elevated. Biochemical, MRI, and neurologic findings were inconsistent with a generalized defect of peroxisomal function and were unique. Analysis of the urine from the recipient of the deceased sibling's liver confirmed the same bile acid synthetic defect. A deficiency in 2-methylacyl-CoA racemase, which is essential for conversion of (25R)THCA to its 25S-isomer, the substrate to initiate peroxisomal beta-oxidation to primary bile acids, was confirmed by DNA analysis revealing a missense mutation (S52P) in the gene encoding this enzyme. Long-term treatment with cholic acid normalized liver enzymes and prevented progression of symptoms. CONCLUSIONS: This genetic defect further highlights bile acid synthetic defects as a cause of neonatal cholestasis.
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Authors | Kenneth D R Setchell, James E Heubi, Kevin E Bove, Nancy C O'Connell, Tracy Brewsaugh, Steven J Steinberg, Ann Moser, Robert H Squires Jr |
Journal | Gastroenterology
(Gastroenterology)
Vol. 124
Issue 1
Pg. 217-32
(Jan 2003)
ISSN: 0016-5085 [Print] United States |
PMID | 12512044
(Publication Type: Case Reports, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Bile Acids and Salts
- Biomarkers
- Cholestanols
- 3,7,12-trihydroxycholestan-26-oic acid
- Racemases and Epimerases
- alpha-methylacyl-CoA racemase
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Topics |
- Bile
(chemistry)
- Bile Acids and Salts
(analysis, biosynthesis, therapeutic use, urine)
- Biomarkers
(analysis)
- Blood
(metabolism)
- Cholestanols
(metabolism)
- DNA Mutational Analysis
- Female
- Gas Chromatography-Mass Spectrometry
- Humans
- Infant, Newborn
- Liver Diseases
(etiology, surgery)
- Liver Transplantation
- Metabolism, Inborn Errors
(complications, drug therapy)
- Mutation
(physiology)
- Peroxisomes
(enzymology)
- Racemases and Epimerases
(genetics)
- Spectrometry, Mass, Fast Atom Bombardment
- Urine
(chemistry)
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