title: Loss of Hep Par 1 immunoreactivity in the livers of patients with carbamoyl phosphate synthetase 1 deficiency.
abstract: The hepatocyte paraffin 1 (Hep Par 1) antibody is widely used as a hepatocyte marker, recognizing carbamoyl phosphate synthetase 1 (CPS1), an essential component of the urea cycle. Various missense, nonsense, and frameshift mutations occur in the CPS1 gene. In neonatal patients with homozygous CPS1 deficiency (CPS1D), urea cycle defects with resulting severe hyperammonemia can be fatal, though liver transplantation provides a complete cure for CPS1D. We performed Hep Par 1 immunostaining in the explanted livers of 10 liver transplant patients with CPS1D. Seven were negative for Hep Par 1 in the hepatocytes and the other three showed normal diffuse granular cytoplasmic staining. As expected, all three Hep Par 1-positive patients had at least one missense mutation, and all four patients who had only nonsense or frameshift mutations were Hep Par 1-negative. The other three patients were unexpectedly negative for Hep Par 1, even though each had one missense mutation. These results suggest that CPS1D can be related to the loss of Hep Par 1 reactivity due to the loss of protein production, a one amino acid substitution resulting in an abortive protein product, or both. Hep Par 1 immunohistochemistry can be used as a simple method to confirm CPS1D.
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Organ Transplant Unit, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Tatsuki R
authors.initials: TR
authors.lastname: Kataoka
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shibayama
authors.affiliation: Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Akinari
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Division of Clinical Pathology, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Nakazawa
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Minamiguchi
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Miyagawa-Hayashino
authors.affiliation: Department of Pediatrics, Osaka City General Hospital, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yorifuji
authors.affiliation: Organ Transplantation Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Mureo
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Organ Transplant Unit, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D020165:Carbamoyl-Phosphate Synthase I Deficiency Disease / Q000378:metabolism* / Q000601:surgery; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008099:Liver / Q000378:metabolism*; D016031:Liver Transplantation; D008297:Male; D020125:Mutation, Missense
chemical_list: D000951:Antigens, Neoplasm; C000600022:HepPar-1 protein, human
keywords: CPS1; Hep Par 1; liver transplantation