Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency

Kevin A. Strauss, Carlos Ferreira, Teodoro Bottiglieri, Xueqing Zhao, Erland Arning, Shucha Zhang, Steven H. Zeisel, Maria L. Escolar, Nancy Presnick, Erik G. Puffenberger, Oliver Vugrek, Lucija Kovacevic, Conrad Wagner, George V. Mazariegos, S. Harvey Mudd, Kyle Soltys

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

A child with severe S-adenosylhomocysteine hydrolase (AHCY) deficiency (AHCY c.428A. >. G, p.Tyr143Cys; c.982. T. >. 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.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalMolecular Genetics and Metabolism
Volume116
Issue number1-2
DOIs
StatePublished - Sep 1 2015

Keywords

  • Liver transplantation
  • Methyltransferases
  • S-adenosylhomocysteine
  • Transsulfuration

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

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    Strauss, K. A., Ferreira, C., Bottiglieri, T., Zhao, X., Arning, E., Zhang, S., Zeisel, S. H., Escolar, M. L., Presnick, N., Puffenberger, E. G., Vugrek, O., Kovacevic, L., Wagner, C., Mazariegos, G. V., Mudd, S. H., & Soltys, K. (2015). Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency. Molecular Genetics and Metabolism, 116(1-2), 44-52. https://doi.org/10.1016/j.ymgme.2015.06.005