Abstract | OBJECTIVES: METHODS: Homozygous or compound heterozygous CYP27A1 mutations were detected in 8 neonatal cholestasis patients by whole exome sequencing, panel sequencing, or Sanger sequencing. Their clinical and biochemical data were retrospectively reviewed. Immunostaining for CYP27A1 was conducted in liver of 4 patients. Mass spectrometry was used to analyze patients' urine samples. RESULTS: All 8 infants had severe cholestasis. Five died from, or were transplanted for, liver failure; 3 cleared their jaundice eventually. Marking for CYP27A1 was weak or absent in 3 of the 4 patient specimens. Mass spectrometry of urine revealed a predominance of sulfated and doubly conjugated (sulfated-glucuronidated) bile alcohols. No patient harbored a putatively pathogenic mutation in genes other than CYP27A1 that have been implicated in cholestatic liver disease. CONCLUSIONS: CTX manifest as neonatal cholestasis has a bile acid profile different from CTX manifest in later life, and thus may be overlooked. Immunostaining, mass spectrometry of urine, and genetic studies can support one another in making the diagnosis. A substantial proportion of CTX patients with severe neonatal cholestasis may die or need liver transplantation. CTX manifest in infancy as severe cholestasis warrants further investigation of biochemical diagnostic criteria and best management.
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Authors | Jing-Yu Gong, Kenneth D R Setchell, Jing Zhao, Wujuan Zhang, Brian Wolfe, Yi Lu, Karolin Lackner, A S Knisely, Neng-Li Wang, Chen-Zhi Hao, Mei-Hong Zhang, Jian-She Wang |
Journal | Journal of pediatric gastroenterology and nutrition
(J Pediatr Gastroenterol Nutr)
Vol. 65
Issue 5
Pg. 561-568
(11 2017)
ISSN: 1536-4801 [Electronic] United States |
PMID | 28937538
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Genetic Markers
- CYP27A1 protein, human
- Cholestanetriol 26-Monooxygenase
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Topics |
- Cholestanetriol 26-Monooxygenase
(genetics, metabolism)
- Cholestasis
(diagnosis, etiology, mortality, surgery)
- Female
- Genetic Markers
- Humans
- Infant, Newborn
- Liver
(metabolism)
- Liver Transplantation
- Male
- Mass Spectrometry
- Mutation
- Retrospective Studies
- Sequence Analysis, DNA
(methods)
- Severity of Illness Index
- Xanthomatosis, Cerebrotendinous
(complications, diagnosis, genetics, metabolism)
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