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

doi:10.1016/j.ymgme.2015.06.005

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 journal › Article › peer-review

27 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 language	English (US)
Pages (from-to)	44-52
Number of pages	9
Journal	Molecular Genetics and Metabolism
Volume	116
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ymgme.2015.06.005
State	Published - Sep 1 2015
Externally published	Yes

Keywords

Liver transplantation
Methyltransferases
S-adenosylhomocysteine
Transsulfuration

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Molecular Biology
Genetics
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ymgme.2015.06.005

Cite this

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

Strauss, KA, Ferreira, C, Bottiglieri, T, Zhao, X, Arning, E, Zhang, S, Zeisel, SH, Escolar, ML, Presnick, N, Puffenberger, EG, Vugrek, O, Kovacevic, L, Wagner, C, Mazariegos, GV, Mudd, SH & Soltys, K 2015, 'Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency', Molecular Genetics and Metabolism, vol. 116, no. 1-2, pp. 44-52. https://doi.org/10.1016/j.ymgme.2015.06.005

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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.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.",

keywords = "Liver transplantation, Methyltransferases, S-adenosylhomocysteine, Transsulfuration",

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

note = "Funding Information: Research at the Clinic for Special Children is supported in part by charitable donations from Amish and Mennonite communities of the Northeastern United States. Dr. Vugrek was supported by funds received from the European Union 's Seventh Framework Programme for Research, Technological Development, and Demonstration under grant agreement No. 316289-InnoMol, FP7-REGPOT-2012-2013-1 . Dedication The authors dedicate this work to the late S. Harvey Mudd, who pioneered the study of transsulfuration and its relevance to human well-being. Harvey possessed a rare combination of humility and wonder that allowed him to wear his scholarship lightly and share it openly. He had a reputation for training his keen intellectual focus on people with real problems, and remained a tireless healer to the end of his life. Harvey taught by example to strive with clarity, alleviate suffering, and always be kind. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc..",

year = "2015",

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day = "1",

doi = "10.1016/j.ymgme.2015.06.005",

language = "English (US)",

volume = "116",

pages = "44--52",

journal = "Molecular Genetics and Metabolism",

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TY - JOUR

T1 - Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency

AU - Strauss, Kevin A.

AU - Ferreira, Carlos

AU - Bottiglieri, Teodoro

AU - Zhao, Xueqing

AU - Arning, Erland

AU - Zhang, Shucha

AU - Zeisel, Steven H.

AU - Escolar, Maria L.

AU - Presnick, Nancy

AU - Puffenberger, Erik G.

AU - Vugrek, Oliver

AU - Kovacevic, Lucija

AU - Wagner, Conrad

AU - Mazariegos, George V.

AU - Mudd, S. Harvey

AU - Soltys, Kyle

N1 - Funding Information: Research at the Clinic for Special Children is supported in part by charitable donations from Amish and Mennonite communities of the Northeastern United States. Dr. Vugrek was supported by funds received from the European Union 's Seventh Framework Programme for Research, Technological Development, and Demonstration under grant agreement No. 316289-InnoMol, FP7-REGPOT-2012-2013-1 . Dedication The authors dedicate this work to the late S. Harvey Mudd, who pioneered the study of transsulfuration and its relevance to human well-being. Harvey possessed a rare combination of humility and wonder that allowed him to wear his scholarship lightly and share it openly. He had a reputation for training his keen intellectual focus on people with real problems, and remained a tireless healer to the end of his life. Harvey taught by example to strive with clarity, alleviate suffering, and always be kind. Publisher Copyright: © 2015 Elsevier Inc..

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - Liver transplantation

KW - Methyltransferases

KW - S-adenosylhomocysteine

KW - Transsulfuration

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ER -

Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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