title: Homozygous SLC25A13 mutation in a Taiwanese patient with adult-onset citrullinemia complicated with steatosis and hepatocellular carcinoma.
abstract: Citrullinemia is a metabolic disorder characterized by elevated plasma concentrations of citrulline and ammonia. Adult-onset citrullinemia (type II, CTLN2) has been attributed to citrin deficiency caused by mutations in the SLC25A13 gene. CTLN2 is associated with a high incidence of hepatocellular carcinoma (HCC) in Japanese. We report a 48-year-old Taiwanese man with citrullinemia, who was in good health until the age of 34 when he had repeated episodes of consciousness disturbance. Hyperammonia (201 micromol/L) was found during an episode of coma. Liver function and electrolyte levels were normal at that time. Serologic markers of viral hepatitis B and C were negative. Analysis of genomic DNA extracted from peripheral blood leukocytes showed homozygous 851del4 mutation in exon 9 of the SLC25A13 gene on chromosome 7q21.3. Fourteen years after disease onset, at the age of 48, he was admitted due to an episode of coma. Abdominal sonography and computed tomography showed a 2.5 cm tumor in the left lobe of the liver, without evidence of liver cirrhosis. Wedge resection of the tumor was performed and grade 2 HCC was diagnosed. The nontumor part of the resected specimen showed chronic persistent hepatitis with moderate steatosis. The results in this case support that both citrin deficiency and steatohepatitis may contribute to hepatocarcinogenesis.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung Shan South Road, Taipei 100, Taiwan.
authors.forename: Ching-Wei
authors.initials: CW
authors.lastname: Tsai
authors.forename: Chih-Chao
authors.initials: CC
authors.lastname: Yang
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chen
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: Mu-Zon
authors.initials: MZ
authors.lastname: Wu
authors.forename: Kao-Lang
authors.initials: KL
authors.lastname: Liu
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
mesh_terms: D044963:Biopsy, Fine-Needle; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D020159:Citrullinemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D003937:Diagnosis, Differential; D004569:Electroencephalography; D005234:Fatty Liver / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D005500:Follow-Up Studies; D006498:Hepatectomy; D006720:Homozygote; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000601:surgery; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D013624:Taiwan; D014057:Tomography, X-Ray Computed
chemical_list: D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C119629:SLC25A13 protein, human; D004247:DNA