A novel inborn error of metabolism detected by elevated methionine and/or galactose in newborn screening: neonatal intrahepatic cholestasis caused by citrin deficiency.
Adult-onset type II citrullinaemia, caused by deficiency of the citrin protein encoded by the SLC25A13 gene, is characterised by a liver-specific argininosuccinate synthetase deficiency. DNA analysis for citrin deficiency revealed that SLC25A13 mutations are the cause of a particular type of neonatal intrahepatic cholestasis. We retrospectively investigated nine infants with cholestatic jaundice of unknown origin, detected by newborn screening over a period of 17 years, to determine the role of SLC25A13 defects in children. The results of the newborn screening were varied; four neonates were positive for hypermethioninaemia, two for hyperphenylalaninaemia, one for hypergalactosaemia and two for both hypermethioninaemia and hypergalactosaemia. Clinical characteristics of the patients were severe intrahepatic cholestasis, hypercitrullinaemia, and fatty liver. The symptoms resolved in all patients by 12 months of age without special treatment other than nutritional management. Although five patients were lost to follow-up, we detected SLC25A13 mutations in the remaining four patients examined.


CONCLUSIONS
the differential diagnosis of cholestatic jaundice of unknown origin in infants should therefore include citrin deficiency. In this paper, we stress the importance of newborn screening to detect infants with neonatal intrahepatic cholestasis caused by citrin deficiency.
Ohura
Toshihiro
T
Department of Paediatrics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. tohura@ped.med.tohoku.ac.jp
Kobayashi
Keiko
K
Abukawa
Daiki
D
Tazawa
Yusaku
Y
Aikawa
Jun-ichiro
J
Sakamoto
Osamu
O
Saheki
Takeyori
T
Iinuma
Kazuie
K
D002780:Cholestasis, Intrahepatic / Q000175:diagnosis / Q000178:diet therapy / Q000209:etiology* / Q000235:genetics; D020159:Citrullinemia / Q000150:complications* / Q000175:diagnosis / Q000178:diet therapy / Q000235:genetics; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005690:Galactose / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D008403:Mass Screening; D008715:Methionine / Q000097:blood; D015997:Neonatal Screening; D010649:Phenylalanine / Q000097:blood; D012189:Retrospective Studies
D010649:Phenylalanine; D008715:Methionine; D005690:Galactose