title: Hepatocellular carcinoma in a research subject with ornithine transcarbamylase deficiency.
abstract: A 66 year old woman who is a manifesting heterozygote for ornithine transcarbamylase deficiency (OTCD) presented with hepatocellular carcinoma (HCC). Fourteen years prior to this presentation she participated in a phase I gene therapy study which used an adenoviral vector, thought to be non-oncogenic, to deliver a normal OTC gene to hepatocytes [1]. A recent review of data collected through a national longitudinal study of individuals with urea cycle defects [2,3] suggests that early urea cycle disorders (UCDs) are associated with hepatocellular damage and liver dysfunction in many cases. This may predispose an affected individual to a substantially increased risk of developing HCC, as has been observed in certain other inborn errors of metabolism. We speculate that the underlying urea cycle defect may be the cause of HCC in this individual.
authors: Gene Therapy Program, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. wilsonjm@mail.med.upenn.edu
authors: James M
authors: JM
authors: Wilson
authors: Oleg A
authors: OA
authors: Shchelochkov
authors: Renata C
authors: RC
authors: Gallagher
authors: Mark L
authors: ML
authors: Batshaw
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D015316:Genetic Therapy; D006579:Heterozygote; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000175:diagnosis / Q000473:pathology*; D009954:Ornithine Carbamoyltransferase / Q000235:genetics / Q000378:metabolism*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000150:complications / Q000235:genetics / Q000628:therapy*; D056806:Urea Cycle Disorders, Inborn / Q000235:genetics / Q000628:therapy*
chemical_list: D009954:Ornithine Carbamoyltransferase