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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Gong, JY; Setchell, KDR; Zhao, J; Zhang, W; Wolfe, B; Lu, Y; Lackner, K; Knisely, AS; Wang, NL; Hao, CZ; Zhang, MH; Wang, JS.
Severe Neonatal Cholestasis in Cerebrotendinous Xanthomatosis: Genetics, Immunostaining, Mass Spectrometry.
J Pediatr Gastroenterol Nutr. 2017; 65(5):561-568
Web of Science PubMed FullText FullText_MUG


Autor/innen der Med Uni Graz:
Knisely Alexander
Lackner Karoline

Dimensions Citations:

Plum Analytics:
Cerebrotendinous xanthomatosis (CTX) is caused by defects in sterol 27-hydroxylase (CYP27A1, encoded by CYP27A1), a key enzyme in the bile acid synthesis pathway. CTX usually presents as neurologic disease in adults or older children. The rare reports of CTX manifest as neonatal cholestasis assess the cholestasis as transient, with patient survival. Our experience differs. 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. 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. 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.
Find related publications in this database (using NLM MeSH Indexing)
Cholestanetriol 26-Monooxygenase - genetics
Cholestanetriol 26-Monooxygenase - metabolism
Cholestasis - diagnosis
Cholestasis - etiology
Cholestasis - mortality
Cholestasis - 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
Xanthomatosis, Cerebrotendinous - diagnosis
Xanthomatosis, Cerebrotendinous - genetics
Xanthomatosis, Cerebrotendinous - metabolism

Find related publications in this database (Keywords)
bile acid synthesis defect
bile alcohol
mass spectrometry
next-generation sequencing
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