Journal Articles

Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency

June 18, 2015

Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiencyMol Genet Metab. 2015 Jun 18, Strauss KA1, Ferreira C2, Bottiglieri T3, Zhao X4, Arning E3, Zhang S4, Zeisel SH4, Escolar ML5, Presnick N6, Puffenberger EG7, Vugrek O8, Kovacevic L8,Wagner C9, Mazariegos GV10, Mudd SH11, Soltys K10.

Author information

  • 1Clinic for Special Children, Strasburg, PA, USA; Franklin and Marshall College, Lancaster, PA, USA; Lancaster General Hospital, Lancaster, PA, USA. Electronic address: kstrauss@clinicforspecialchildren.org.
  • 2National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • 3Center of Metabolomics, Institute of Metabolic Disease, Baylor Research Institute, Dallas, TX, USA.
  • 4Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, USA.
  • 5Program 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.
  • 6Clinic for Special Children, Strasburg, PA, USA.
  • 7Clinic for Special Children, Strasburg, PA, USA; Franklin and Marshall College, Lancaster, PA, USA.
  • 8Translational Medicine Group, Ruđer Bošković Institute, Zagreb, Croatia.
  • 9Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • 10Hillman 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.
  • 11Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD, USA.

Abstract

A child with severe S-adenosylhomocysteine hydrolase (AHCY) deficiency (AHCY c.428A>G, p.Tyr143Cys; c.982T>G, p.Tyr328Asp) presented at 8months 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 40months 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±0.79mol:mol (control 4.10±2.11mol:mol). Blood methionine and AdoMet were normal and stable during 6months 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.

Copyright © 2015 Elsevier Inc. All rights reserved.

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