• Clinical science

Vitamin B12 deficiency (Cobalamin deficiency)


Vitamin B12 (cobalamin) plays an essential role in enzymatic reactions responsible for red blood cell (RBC) formation and proper myelination of the nervous system. Thus, a deficiency of vitamin B12 may lead to megaloblastic anemia and a wide range of neurological disturbances. Deficiency may be caused by malabsorption, malnutrition, or an increased demand. The most common underlying cause of vitamin B12 deficiency is pernicious anemia, an autoimmune disorder characterized by the absence of intrinsic factor (IF). IF is a protein that is crucial for vitamin B12 absorption. Patients present with signs of anemia (e.g., fatigue) and/or neurological manifestations such as paresthesia, spasticity, ataxia, and neuropsychiatric disorders. After detecting low serum vitamin B12 levels, the diagnostic approach consists of identifying the underlying cause by measuring autoantibodies and possibly conducting a Schilling test. When testing patients with suspected vitamin B12 deficiency, it is important to remember that folate deficiency also causes megaloblastic anemia. However, only vitamin B12 deficiency can be accompanied by neuropathy and exhibits elevated levels of methylmalonic acid (MMA). Treatment consists of parenteral supplementation; depending on the underlying cause, long-term supplementation may be needed.




Dysfunctional biochemical reactions

Folate deficiency also leads to low levels of THF and resulting megaloblastic anemia!

Pernicious anemia


Clinical features

Always consider vitamin B12 deficiency when evaluating patients with dementia!



Hematological findings



Differential diagnoses

Other causes of macrocytic anemia

Starting folate treatment before excluding vitamin B12 deficiency may correct anemia, but could worsen neuropathy!

In contrast to vitamin B12 deficiency, folic acid deficiency is generally not associated with neurological symptoms!

Other causes of neuropathy


The differential diagnoses listed here are not exhaustive.