A new Caucasian case of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD): A clinical, molecular, and functional study

Giuseppe Fiermonte, Giovanni Parisi, Diego Martinelli, Francesco De Leonardis, Giuliano Torre, Ciro Leonardo Pierri, Alessia Saccari, Francesco Massimo Lasorsa, Angelo Vozza, Ferdinando Palmieri, Carlo Dionisi-Vici

Research output: Contribution to journalArticlepeer-review

Abstract

Citrin is the liver-specific isoform of the mitochondrial aspartate/glutamate carrier (AGC2). AGC2 deficiency is an autosomal recessive disorder with two age related phenotypes: neonatal intrahepatic cholestasis (NICCD, OMIM#. 605814) and adult-onset type II citrullinemia (CTLN2, OMIM#. 603471). NICCD arises within the first few weeks of life resulting in prolonged cholestasis and metabolic abnormalities including aminoacidemia and galactosuria. Usually symptoms disappear within the first year of life, thus making a diagnosis difficult after this time. In this study we report a new Caucasian case of NICCD, a seven week old Romanian boy with prolonged jaundice. Sequencing of the AGC2 gene showed a novel homozygous missense double-nucleotide (doublet) mutation, which produces the change of the glycine at position 437 into glutamate. Functional studies, carried out on the recombinant mutant protein, for the first time demonstrated, that NICCD is caused by a reduced transport activity of AGC2. The presence of AGC2 deficiency in other ethnic groups besides Asian population suggests further consideration for NICCD diagnosis of any neonate with an unexplained cholestasis; a prompt diagnosis is crucial to resolve the metabolic decompensation with an appropriate dietary treatment.

Original languageEnglish
Pages (from-to)501-506
Number of pages6
JournalMolecular Genetics and Metabolism
Volume104
Issue number4
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Aspartate/glutamate carrier
  • NICCD
  • Urea cycle defect

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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