Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle.
Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.
Saheki
Takeyori
T
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. takesah@m.kufm.kagoshima-u.ac.jp
Kobayashi
Keiko
K
Iijima
Mikio
M
Horiuchi
Masahisa
M
Begum
Laila
L
Jalil
Md Abdul
MA
Li
Meng Xian
MX
Lu
Yao Bang
YB
Ushikai
Miharu
M
Tabata
Ayako
A
Moriyama
Mitsuaki
M
Hsiao
Kwang-Jen
KJ
Yang
Yanling
Y
D000328:Adult; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D020159:Citrullinemia / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005260:Female; D005787:Gene Frequency; D006505:Hepatitis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008099:Liver / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D027361:Organic Anion Transporters / Q000172:deficiency*; D014508:Urea / Q000378:metabolism*
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; D014508:Urea