Time course of acylcarnitine elevation in neonatal intrahepatic cholestasis caused by citrin deficiency

J Inherit Metab Dis. 2006 Aug;29(4):551-5. doi: 10.1007/s10545-006-0250-y. Epub 2006 May 30.

Abstract

Citrin is a mitochondrial membrane aspartate-glutamate carrier, and citrin deficiency causes both hyperammonaemia in adults (adult-onset type II citrullinaemia, CTLN2) and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), with metabolic derangements in gluconeogenesis, aerobic glycolysis, urea synthesis, UDP-galactose epimerase activity, and possibly fatty acid synthesis and utilization. Through neonatal screening and case review, four patients with NICCD who had an acylcarnitine profile during infancy were all found to have an elevation of free carnitine, C2-carnitine, and long-chain acylcarnitines. These metabolic abnormalities appeared after the rise of citrulline and bilirubin, but before the elevation of alanine aminotransferase and aspartate aminotransferase. Although the rise of free carnitine and acylcarnitines seems to be a benign condition, the sequential changes of these metabolic derangements may give clues to the pathogenesis of this interesting disorder.

MeSH terms

  • Alanine / metabolism
  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Calcium-Binding Proteins / deficiency*
  • Carnitine / analogs & derivatives*
  • Carnitine / biosynthesis
  • Carnitine / metabolism
  • Cholestasis, Intrahepatic / etiology*
  • Cholestasis, Intrahepatic / metabolism*
  • Humans
  • Infant
  • Infant, Newborn
  • Mass Spectrometry / methods
  • Membrane Transport Proteins / chemistry
  • Models, Biological
  • Neonatal Screening
  • Organic Anion Transporters / deficiency*
  • Time Factors

Substances

  • Calcium-Binding Proteins
  • Membrane Transport Proteins
  • Organic Anion Transporters
  • acylcarnitine
  • citrin
  • Alanine
  • Carnitine