title: Mutation in the sterol 27-hydroxylase gene associated with fatal cholestasis in infancy.
abstract: BACKGROUND
  Inborn errors of bile acid synthesis are rare but potentially treatable causes of neonatal cholestasis. We here present a cholestatic infant with an ongoing cytomegalovirus infection who despite intensive treatment died of severe liver disease at 4 months of age.
  
  
  METHODS
  The urinary steroids were investigated by electrospray mass spectrometry and gas chromatography mass spectrometry. Oxysterols in plasma were analysed by isotope dilution mass spectrometry. Mutations in the sterol 27-hydroxylase gene were detected by PCR.
  
  
  RESULTS
  Glucuronidated bile alcohols, which are known to be excreted by patients with cerebrotendinous xanthomatosis (CTX) were detected in the urine. Analysis of plasma revealed markedly reduced levels of 27-hydroxycholesterol. Mutation analysis showed the presence of a stop codon in exon 7, confirming the diagnosis of CTX, a rare disease not previously diagnosed in Sweden.
  
  
  CONCLUSIONS
  Fetal and neonatal deaths among siblings of patients with CTX have been reported previously and the present case supports the contention that reduced activity of the sterol 27-hydroxylase may predispose to the development of neonatal cholestasis. The associated viral infection may have further precipitated the liver disease. Since CTX, like other inborn errors of bile acid synthesis may be treated with bile acids an early diagnosis is essential. Thus, the analysis of urine by electrospray mass spectrometry is highly recommended in the investigation of patients with neonatal cholestasis.
authors.affiliation: Department of Clinical Chemistry, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: von Bahr
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Van't Hooft
authors.forename: Gunvor
authors.initials: G
authors.lastname: Alvelius
authors.forename: Antal
authors.initials: A
authors.lastname: Nemeth
authors.forename: Jan
authors.initials: J
authors.lastname: Sjövall
authors.forename: Björn
authors.initials: B
authors.lastname: Fischler
mesh_terms: D053493:Cholestanetriol 26-Monooxygenase; D002779:Cholestasis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D017809:Fatal Outcome; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000235:genetics*; D019294:Xanthomatosis, Cerebrotendinous / Q000175:diagnosis* / Q000235:genetics
chemical_list: D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase