DESCRIPTION

• Macrocytosis refers to a blood condition in which red blood cells (RBCs) are larger than normal. It is reported in terms of mean corpuscular volume (MCV).
• The normal range of MCV in children varies by age.
• Normal MCV for most children and adolescents is approximately 75 to 95 fL. Of note, the normal MCV in neonates and infants is much higher (approximately 90 to 105 fL) due to the high percentage of hemoglobin F.
• Macrocytosis with associated anemia (macrocytic anemia) can be broadly classified as megaloblastic or nonmegaloblastic anemia.
• Megaloblastic anemia is a specific subset of macrocytic anemia, characteristic by hypersegmented (nucleus with 5 to 6 lobes) neutrophils in the peripheral blood and bone marrow.

EPIDEMIOLOGY

• The true incidence and prevalence are unknown. It is rare in children in North America but is more common in older adults.
• The most frequent causes of megaloblastic anemia are disorders resulting from nutritional deficiencies, such as vitamin B₁₂ (cobalamin) or folate.

ETIOLOGY

• The most common etiologies of megaloblastic anemia are vitamin B₁₂ or folate deficiencies.
• Medications or severe copper deficiencies are another less common cause of megaloblastic anemia.
• Pernicious anemia
  • Common cause of megaloblastic anemia in adults but rare in children
  • A type of vitamin B₁₂ deficiency anemia and is caused by a decrease in the secretion of intrinsic factor (IF) by gastric parietal cells in the setting of autoimmune atrophic gastritis; IF is a protein that is essential for absorption of vitamin B₁₂ in the ileum.
• Nonmegaloblastic macrocytic anemias can be due to
  • Alcohol intake
  • Liver disease (with normal vitamin B₁₂ and folate)
  • Diamond-Blackfan anemia
  • Myelodysplastic syndrome

RISK FACTORS

• Breastfed infants whose mothers are strictly vegetarian or malnourished
• Infants who are on a goat milk diet exclusively
• Children with chronic malnutrition, especially with developmental delays

GENERAL PREVENTION

• Balanced diet for children and breastfeeding mothers
• Vitamin supplement for breastfeeding mothers with a strictly vegan diet

PATHOPHYSIOLOGY

• Megaloblastic anemia is a direct result of ineffective or dysplastic erythropoiesis caused by a defect in DNA synthesis that interferes with cellular proliferation and maturation.
• When vitamin B₁₂ or folate is deficient, RBC proliferation and maturation results in large erythroblasts with nuclear/cytoplasmic asynchrony. The erythroblasts become large, oval-shaped, and contain a characteristic immature, lacy nucleus. These bone marrow features are called “megaloblastic.”

COMMONLY ASSOCIATED CONDITIONS

Megaloblastic anemia is commonly associated with neurologic symptoms (sensory and proprioceptive changes of lower extremities, spasticity, ataxia), atrophic glossitis, and stomatitis.