title: Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency.
abstract: A child with severe S-adenosylhomocysteine hydrolase (AHCY) deficiency (AHCY c.428A>G, p.Tyr143Cys; c.982T>G, p.Tyr328Asp) presented at 8 months of age with growth failure, microcephaly, global developmental delay, myopathy, hepatopathy, and factor VII deficiency. Plasma methionine, S-adenosylmethionine (AdoMet), and S-adenosylhomocysteine (AdoHcy) were markedly elevated and the molar concentration ratio of AdoMet:AdoHcy, believed to regulate a myriad of methyltransferase reactions, was 15% of the control mean. Dietary therapy failed to normalize biochemical markers or alter the AdoMet to AdoHcy molar concentration ratio. At 40 months of age, the proband received a liver segment from a healthy, unrelated living donor. Mean AdoHcy decreased 96% and the AdoMet:AdoHcy concentration ratio improved from 0.52±0.19 to 1.48±0.79 mol:mol (control 4.10±2.11 mol:mol). Blood methionine and AdoMet were normal and stable during 6 months of follow-up on an unrestricted diet. Average calculated tissue methyltransferase activity increased from 43±26% to 60±22%, accompanied by signs of increased transmethylation in vivo. Factor VII activity increased from 12% to 100%. During 6 postoperative months, head growth accelerated 4-fold and the patient made promising gains in gross motor, language, and social skills.
authors.affiliation: Clinic for Special Children, Strasburg, PA, USA; Franklin and Marshall College, Lancaster, PA, USA; Lancaster General Hospital, Lancaster, PA, USA. Electronic address: kstrauss@clinicforspecialchildren.org.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Strauss
authors.affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Center of Metabolomics, Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Teodoro
authors.initials: T
authors.lastname: Bottiglieri
authors.affiliation: Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Center of Metabolomics, Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Erland
authors.initials: E
authors.lastname: Arning
authors.affiliation: Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
authors.forename: Shucha
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
authors.affiliation: Program for the Study of Neurodevelopment in Rare Disorders and Center for Rare Disease Therapy, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Escolar
authors.affiliation: Clinic for Special Children, Strasburg, PA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Presnick
authors.affiliation: Clinic for Special Children, Strasburg, PA, USA; Franklin and Marshall College, Lancaster, PA, USA.
authors.forename: Erik G
authors.initials: EG
authors.lastname: Puffenberger
authors.affiliation: Translational Medicine Group, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vugrek
authors.affiliation: Translational Medicine Group, Ruđer Bošković Institute, Zagreb, Croatia.
authors.forename: Lucija
authors.initials: L
authors.lastname: Kovacevic
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.affiliation: Hillman Center for Pediatric Transplantation, Thomas E. Starzl Transplant Institute and Center for Rare Disease Therapy, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: George V
authors.initials: GV
authors.lastname: Mazariegos
authors.affiliation: Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD, USA.
authors.forename: S Harvey
authors.initials: SH
authors.lastname: Mudd
authors.affiliation: Hillman Center for Pediatric Transplantation, Thomas E. Starzl Transplant Institute and Center for Rare Disease Therapy, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Soltys
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000503:physiopathology / Q000601:surgery* / Q000628:therapy*; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology; D004035:Diet Therapy; D005260:Female; D050938:Glycine N-Methyltransferase / Q000172:deficiency*; D006257:Head / Q000254:growth & development / Q000473:pathology; D006801:Humans; D016031:Liver Transplantation; D008715:Methionine / Q000097:blood; D008831:Microcephaly / Q000209:etiology; D009135:Muscular Diseases / Q000209:etiology; D020641:Polymorphism, Single Nucleotide; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood
chemical_list: D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D050938:Glycine N-Methyltransferase
keywords: Liver transplantation; Methyltransferases; S-adenosylhomocysteine; Transsulfuration