Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

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 Doi: 10.1097/MPG.0000000000001730
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Knisely Alexander

Lackner Karoline

Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Abstract:

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

CYP27A1

mass spectrometry

next-generation sequencing

© Med Uni Graz • Imprint