Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation.
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.
Tamamori
Akiko
A
Department of Paediatrics, Fujiidera City Hospital, Fujiidera, Japan.
Okano
Yoshiyuki
Y
Ozaki
Hajime
H
Fujimoto
Akie
A
Kajiwara
Masue
M
Fukuda
Kazuyoshi
K
Kobayashi
Keiko
K
Saheki
Takeyori
T
Tagami
Yasuko
Y
Yamano
Tsunekazu
T
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
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