Vitamin B12 Deficiency Causes Neutropenia
The correct answer is c. vitamin B12 - deficiency of this vitamin directly causes neutropenia through dysgranulopoiesis (abnormal neutrophil production and maturation). 1, 2, 3
Mechanism and Clinical Evidence
Vitamin B12 deficiency leads to neutropenia through megaloblastic changes in bone marrow that disrupt normal granulocyte production. 3 The deficiency causes:
- Nuclear-cytoplasmic asynchrony in developing neutrophils and their precursors 3
- Disrupted neutrophil maturation with megaloblastic changes visible on bone marrow examination 3
- Increased peripheral myeloid colony-forming cells despite low circulating neutrophils, indicating ineffective granulopoiesis 3
- Phagocytosis of disrupted neutrophils by marrow macrophages before they can be released 3
Clinical Presentation
Vitamin B12 deficiency presenting with neutropenia typically shows:
- Absolute neutrophil counts that can be severely reduced 1, 2
- Associated findings of folate and B12 levels should be checked together, as both can cause similar hematologic abnormalities 1
- In pediatric series, vitamin B12 deficiency accounted for 5.3% of neutropenia cases (median B12 level: 168 pg/ml) 2
- Neutropenia may be accompanied by anemia and other cytopenias as part of megaloblastic changes 3
Treatment Response
High-dose vitamin B12 supplementation corrects neutropenia caused by B12 deficiency, with normalization of neutrophil counts typically occurring within weeks to months of replacement therapy. 1, 2
- Neutropenia responds specifically to B12 replacement when this is the underlying cause 1
- Recovery occurs even in severe cases with profound neutropenia 1
- The response confirms the diagnosis when other causes have been excluded 1
Diagnostic Approach
When evaluating unexplained neutropenia:
- Screen for vitamin B12 deficiency along with folate levels in all patients with refractory neutropenia 1
- This is especially critical in patients with malabsorption syndromes, chronic graft-versus-host disease, or gastrointestinal disorders 1, 4
- Bone marrow examination may show megaloblastic changes but is not required if B12 deficiency is documented and responds to treatment 3
Why Other Options Are Incorrect
Vitamin B6 (pyridoxine) deficiency can cause neutropenia but this is extremely rare - only isolated case reports exist, and it is not a recognized standard cause 1. Copper deficiency (not listed as an option) is actually more commonly associated with neutropenia than B6 4.
Vitamins A and C deficiencies do not cause neutropenia as a primary manifestation - these are not recognized etiologies in standard evaluations of neutropenia 2.