Liver transplantation for treatment of severe S-adenosylhomocysteine hydrolase deficiency
| Autor: | Conrad Wagner, George V. Mazariegos, Xueqing Zhao, Shucha Zhang, Kevin A. Strauss, Carlos Ferreira, Maria L. Escolar, Nancy Presnick, Oliver Vugrek, Lucija Kovačević, Erland Arning, Teodoro Bottiglieri, Steven H. Zeisel, S. Harvey Mudd, Erik G. Puffenberger, Kyle Soltys |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
S-Adenosylmethionine Molar concentration Methyltransferase Diet therapy Endocrinology Diabetes and Metabolism medicine.medical_treatment Developmental Disabilities Transsulfuration Glycine N-Methyltransferase Biology Liver transplantation Biochemistry Polymorphism Single Nucleotide chemistry.chemical_compound Endocrinology Methionine Muscular Diseases Internal medicine transsulfuration methyltransferases S-adenosylhomocysteine liver transplantation Genetics medicine Humans Molecular Biology Amino Acid Metabolism Inborn Errors Glycine N-methyltransferase S-Adenosylhomocysteine Liver Transplantation chemistry Child Preschool Microcephaly Female Transmethylation Head Diet Therapy |
| Zdroj: | Molecular genetics and metabolism. 116(1-2) |
| ISSN: | 1096-7206 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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