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 - 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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U2 - 10.1016/j.ymgme.2015.06.005
DO - 10.1016/j.ymgme.2015.06.005
M3 - Article
C2 - 26095522
AN - SCOPUS:84940896702
SN - 1096-7192
VL - 116
SP - 44
EP - 52
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
ER -