Which vitamin deficiency is associated with macrocytic anemia and methylmalonic acidemia?

The association of macrocytic anemia and methylmalonic acidemia is primarily indicative of a deficiency in cobalamin, commonly known as vitamin B12. This vitamin plays a crucial role in DNA synthesis and the metabolism of certain fatty acids and amino acids, including the conversion of methylmalonyl-CoA to succinyl-CoA. A deficiency in vitamin B12 leads to impaired DNA synthesis, resulting in the production of larger than normal red blood cells, a condition known as macrocytic anemia.

Moreover, cobalamin deficiency also leads to the accumulation of methylmalonic acid due to the disrupted metabolism of fatty acids and amino acids. Elevated levels of methylmalonic acid in patients suggest that vitamin B12 is not available to facilitate the conversion processes that normally utilize this compound, resulting in its increased concentration in the body.

In contrast to vitamin B12, deficiencies in the other vitamins listed do not lead to both macrocytic anemia and methylmalonic acidemia. For example, folate deficiency typically presents with macrocytic anemia but does not involve the accumulation of methylmalonic acid. Thiamine (B1) deficiency is linked to conditions such as Wernicke's encephalopathy and beriberi, but has no connection