Alcohol abuse: an important cause of severe hyperhomocysteinemia

Alcohol has complex direct effects on homocysteine metabolism, which are incompletely understood, and indirect effects mediated by interactions with vitamin metabolism and other factors. Both transmethylation and transsulfuration pathways are affected. Alcohol abuse is a common cause of hyperhomocysteinemia that often fluctuates and is sometimes severe. The causative role of alcohol in hyperhomocysteinemia is often overlooked by clinicians when evaluating patients and by investigators when conducting surveys. A married couple with severe hyperhomocysteinemia owing to surreptitious alcohol abuse, a case study illustrating many of these issues, is presented. A steep rise in S-adenosylhomocysteine as well as homocysteine levels was demonstrated with increased alcohol ingestion, with a decreased S-adenosylmethionine:S-adenosylhomocysteine ratio. Both patients had severe neurologic symptoms as well as macrocytic red blood cells, which, along with the high homocysteine levels, were misattributed to cobalamin deficiency, in one case despite serum cobalamin levels that were normal.