Publication: Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among thai infants
Issued Date
2012
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eng
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Mahidol University
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BioMed Central
Bibliographic Citation
BMC Gastroenterology. Vol. 12, (2012), 141
Suggested Citation
Suporn Treepongkaruna, Suttiruk Jitraruch, Porawee Kodcharin, Dussadee Charoenpipop, Pim Suwannarat, Paneeya Pienvichit, Keiko Kobayashi, Duangrurdee Wattanasirichaigoon1 Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among thai infants. BMC Gastroenterology. Vol. 12, (2012), 141. doi:10.1186/1471-230X-12-141 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/2693
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Title
Neonatal intrahepatic cholestasis caused by citrin deficiency: prevalence and SLC25A13 mutations among thai infants
Abstract
Background: The most common causes of cholestatic jaundice are biliary atresia and idiopathic neonatal hepatitis
(INH). Specific disorders underlying INH, such as various infectious and metabolic causes, including neonatal
intrahepatic cholestasis caused by citrin deficiency (NICCD) especially, in East Asian populations are increasingly
being identified. Since most NICCD infants recovered from liver disease by 1 year of age, they often are
misdiagnosed with INH, leading to difficulty in determining the true prevalence of NICCD. Mutation(s) of human
SLC25A13 gene encoding a mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), can lead to AGC2
deficiency, resulting in NICCD and an adult-onset fatal disease namely citrullinemia type II (CTLN2). To study the
prevalence of NICCD and SLC25A13 mutations in Thai infants, and to compare manifestations of NICCD and
non-NICCD, infants with idiopathic cholestatic jaundice or INH were enrolled. Clinical and biochemical data were
reviewed. Urine organic acid and plasma amino acids profiles were analyzed. PCR-sequencing of all 18 exons of
SLC25A13 and gap PCR for the mutations IVS16ins3kb and Ex16+74_IVS17-32del516 were performed. mRNA were
analyzed in selected cases with possible splicing error.
Results: Five out of 39 (12.8%) unrelated infants enrolled in the study were found to have NICCD, of which three
had homozygous 851del4 (GTATdel) and two compound heterozygous 851del4/IVS16ins3kb and 851del4/
1638ins23, respectively. Two missense mutations (p.M1? and p.R605Q) of unknown functional significance were
identified. At the initial presentation, NICCD patients had higher levels of alkaline phosphatase (ALP) and
alpha-fetoprotein (AFP) and lower level of alanine aminotransferase (ALT) than those in non-NICCD patients
(p< 0.05). NICCD patients showed higher citrulline level and threonine/serine ratio than non-NICCD infants
(p< 0.05). Fatty liver was found in 2 NICCD patients. Jaundice resolved in all NICCD and in 87.5% of non-NICCD
infants at the median age of 9.5 and 4.0 months, respectively.
Conclusion: NICCD should be considered in infants with idiopathic cholestasis. The preliminary estimated
prevalence of NICCD was calculated to be 1/48,228 with carrier rate of 1/110 among Thai infants. However, this
number may be underestimated and required further analysis with mutation screening in larger control population
to establish the true prevalence of NICCD and AGC2 deficiency.