American Board of Internal Medicine (ABIM) Certification Practice Exam

An elevated homocysteine level is sensitive for which deficiency?

1. Iron deficiency

2. Cobalamin deficiency

3. Folate deficiency

4. Vitamin D deficiency

The correct answer is: Folate deficiency

An elevated homocysteine level is indeed sensitive to deficiencies in both cobalamin (vitamin B12) and folate (vitamin B9), but it is most commonly associated with folate deficiency in clinical practice due to the role of folate in the metabolic pathway that converts homocysteine to methionine. In the process of methylation, folate-derived methyl groups are essential for the conversion of homocysteine, a potentially toxic amino acid, to methionine. When there is insufficient folate, this conversion is impaired, leading to an accumulation of homocysteine in the bloodstream. Elevated homocysteine levels have been noted to correlate with cardiovascular disease risk and are indicative of a necessary nutrient deficiency that can be easily addressed with dietary sources or supplementation of folate. While cobalamin deficiency also leads to elevated homocysteine levels, it often accompanies an elevation in methylmalonic acid, making it a less sensitive marker for deficiency in cobalamin alone compared to homocysteine in the context of folate shortage. Thus, in assessing elevated homocysteine levels, it serves as a more direct indicator of folate deficiency in many clinical settings.