5. The deficiency of cyanocobaltamine (Vitamin B12) leads to-
(1) Microcytic anemia
(2) Megaloblastic Anemia

(3) Thalsemmia
(4) Hypochoramtosis

Introduction

Vitamin B12, also known as cyanocobalamin, is a crucial nutrient that plays an essential role in DNA synthesis, red blood cell formation, and neurological function. Deficiency of vitamin B12 leads to serious health problems, among which megaloblastic anemia is the most prominent type of anemia seen. This article explores the causes, pathophysiology, symptoms, diagnosis, and treatment of vitamin B12 deficiency, focusing on why it leads to megaloblastic anemia rather than other anemia types such as microcytic anemia or diseases like thalassemia and hypochromatosis.

What is Vitamin B12 (Cyanocobalamin)?

Vitamin B12 is a water-soluble vitamin essential for the normal functioning of the brain and nervous system and for the formation of blood. It acts as a cofactor in important enzymatic reactions involved in the production of DNA and the metabolism of fatty acids and amino acids.

Humans obtain vitamin B12 primarily through animal-based foods, and its absorption requires a special protein called intrinsic factor, secreted by the stomach.

Causes of Vitamin B12 Deficiency

Vitamin B12 deficiency may result from:

• Poor dietary intake, especially in vegans or malnourished individuals.

• Malabsorption syndromes like pernicious anemia, atrophic gastritis, or gastrointestinal surgeries.

• Disorders like Crohn’s disease and celiac disease.

• Certain medications affecting absorption.

• Increased requirement during pregnancy or breastfeeding.

Why Vitamin B12 Deficiency Causes Megaloblastic Anemia

Vitamin B12 deficiency interferes with DNA synthesis essential for red blood cell production. Specifically, it acts as a cofactor for methionine synthase that converts homocysteine to methionine, a crucial step in DNA precursor synthesis. Without adequate B12, DNA replication slows down, leading to defective maturation of red blood cells causing them to become abnormally large—termed megaloblasts. These large red blood cells cannot function properly leading to anemia.

This defective DNA synthesis also affects other rapidly dividing cells like white blood cells, leading to hypersegmented neutrophils observable in blood smears.

Symptoms of Megaloblastic Anemia Due to Vitamin B12 Deficiency

The clinical manifestations include:

• Fatigue, weakness, and pallor due to anemia.

• Neurological symptoms like numbness, tingling, difficulty walking (ataxia), and memory problems caused by myelin sheath damage.

• Glossitis (red, beefy tongue).

• Jaundice due to increased red blood cell breakdown.

• Psychological symptoms such as irritability, depression, and in severe cases dementia.

Differentiating from Other Anemias and Disorders

• Microcytic anemia (Option 1): Characterized by small red blood cells and is caused mainly by iron deficiency or thalassemia. B12 deficiency does not cause microcytic anemia.

• Thalassemia (Option 3): A genetic disorder affecting hemoglobin synthesis, unrelated to vitamin B12 status.

• Hypochromatosis (Option 4): Refers to an abnormally low hemoglobin content in red blood cells, often related to iron deficiency, not B12 deficiency.

Diagnosis

Diagnostic steps for vitamin B12 deficiency anemia involve:

• Complete blood count (CBC) showing macrocytic anemia with elevated mean corpuscular volume (MCV >100 fL).

• Peripheral blood smear showing megaloblasts and hypersegmented neutrophils.

• Serum vitamin B12 level measurement (deficient if below 200 pg/mL).

• Elevated levels of methylmalonic acid (MMA) and homocysteine help confirm the diagnosis.

• Differentiation from folate deficiency is important, as both cause megaloblastic anemia but have different treatments.

Treatment

Treatment typically involves supplementation of vitamin B12, either orally or via intramuscular injections depending on severity and cause. Early treatment can reverse hematologic abnormalities and prevent permanent neurological damage.