title: Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation.
abstract: Adult-onset type 2 citrullinaemia (CTLN2) is caused by a deficiency of the citrin protein encoded by the SLC25A13 gene. Citrin, an aspartate glutamate carrier in mitochondria, is an essential component of the malate-aspartate NADH shuttle. Recently, citrin deficiency has been reported to manifest as neonatal intrahepatic cholestasis. We report here five cases with neonatal intrahepatic cholestasis caused by citrin deficiency. Genetic diagnosis revealed compound heterozygotes of 851del4/IVS11 + 1G-->A in two patients, IVS11 + 1G-->A/E601X, and IVS11 + 1G-->A/unknown in each one patient and homozygote for S225X in one patient. All cases revealed high levels of alpha-fetoprotein, which are not observed in CTLN2 patients. The condition was self-limiting and spontaneously disappeared after 5-7 months of age in four patients. However, one patient developed hepatic dysfunction from the age of 6 months and required a living-related liver transplantation at the age of 10 months. The patient showed complete recovery after transplantation, and now at the age of 3 years, shows normal growth and mental development.
  
  
  CONCLUSIONS
  we report the first case of neonatal intrahepatic cholestasis caused by citrin deficiency with severe hepatic dysfunction requiring a living-related liver transplantation. Patients with this disorder should be followed up carefully, even during infancy.
authors.affiliation: Department of Paediatrics, Fujiidera City Hospital, Fujiidera, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Tamamori
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Okano
authors.forename: Hajime
authors.initials: H
authors.lastname: Ozaki
authors.forename: Akie
authors.initials: A
authors.lastname: Fujimoto
authors.forename: Masue
authors.initials: M
authors.lastname: Kajiwara
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Fukuda
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Takeyori
authors.initials: T
authors.lastname: Saheki
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tagami
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Yamano
mesh_terms: D002135:Calcium-Binding Proteins / Q000172:deficiency*; D002780:Cholestasis, Intrahepatic / Q000151:congenital / Q000209:etiology* / Q000601:surgery*; D020159:Citrullinemia / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics; D009154:Mutation; D027361:Organic Anion Transporters / Q000172:deficiency*; D012075:Remission, Spontaneous
chemical_list: D002135:Calcium-Binding Proteins; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; C008822:citrin