Background: The etiology of liver disease remains elusive in some adults presenting with severe hepatic dysfunction. Methods and 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. Conclusion: 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.
- Exome sequencing
- Hepatocellular carcinoma
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology