title: Adult-onset liver disease and hepatocellular carcinoma in S-adenosylhomocysteine hydrolase deficiency.
abstract: BACKGROUND
  The etiology of liver disease remains elusive in some adults presenting with severe hepatic dysfunction.
  
  
  RESULTS
  Here we describe a woman of Pakistani descent who had elevated aminotransferases at age 23. She developed muscle weakness in her mid-20s, and was diagnosed with hepatocellular carcinoma at age 29. She died without a diagnosis at age 32 after having a liver transplant. Exome sequencing revealed that she was homozygous for a missense mutation (R49H) in AHCY, the gene encoding S-adenosylhomocysteine (SAH) hydrolase. SAH hydrolase catalyzes the final step in conversion of methionine to homocysteine and inactivating mutations in this enzyme cause a rare autosomal recessive disorder, SAH hydrolase deficiency, that typically presents in infancy. An asymptomatic 7-year old son of the proband is also homozygous for the AHCY-R49H mutation and has elevated serum aminotransferase levels, as well as markedly elevated serum levels of SAH, S-adenosylmethionine (SAM), and methionine, which are hallmarks of SAH hydrolase deficiency.
  
  
  CONCLUSIONS
  This report reveals several new aspects of SAH hydrolase deficiency. Affected women with SAH hydrolase deficiency can give birth to healthy children. SAH hydrolase deficiency can remain asymptomatic in childhood, and the disorder can be associated with early onset hepatocellular carcinoma. The measurement of serum amino acids should be considered in patients with liver disease or hepatocellular carcinoma of unknown etiology.
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, United States; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Stefan.stender@utsouthwestern.edu.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stender
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, United States; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Rima.shah@utsouthwestern.edu.
authors.forename: Rima S
authors.initials: RS
authors.lastname: Chakrabarti
authors.affiliation: McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Chao.xing@utsouthwestern.edu.
authors.forename: Chao
authors.initials: C
authors.lastname: Xing
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Garrett.gotway@utsouthwestern.edu.
authors.forename: Garrett
authors.initials: G
authors.lastname: Gotway
authors.affiliation: McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Jonathan.cohen@utsouthwestern.edu.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Cohen
authors.affiliation: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, United States; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, United States; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Helen.hobbs@utsouthwestern.edu.
authors.forename: Helen H
authors.initials: HH
authors.lastname: Hobbs
mesh_terms: D043383:Adenosylhomocysteinase / Q000235:genetics*; D000328:Adult; D017668:Age of Onset; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D015870:Gene Expression; D050938:Glycine N-Methyltransferase / Q000172:deficiency* / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008113:Liver Neoplasms / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D012435:S-Adenosylhomocysteine / Q000097:blood; D016415:Sequence Alignment; D000637:Transaminases / Q000097:blood / Q000235:genetics
chemical_list: D012435:S-Adenosylhomocysteine; D050938:Glycine N-Methyltransferase; D000637:Transaminases; D043383:Adenosylhomocysteinase
keywords: AHCY; Exome sequencing; Genetics; Hepatocellular carcinoma; Methionine