This document discusses megaloblastic anemia caused by vitamin B12 or folate deficiency. It provides details on the absorption and roles of vitamin B12 and folate, causes of deficiency including inadequate intake and impaired absorption, clinical manifestations such as anemia and neurological symptoms, diagnostic tests including blood tests and Schilling test, and treatment involving parenteral vitamin B12 supplementation or oral folic acid.

1. Megaloblastic Anemia
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2. Effect of cobalamin and folate on DNA synthesis

3. Actions of cobalamin

4. Vitamin B12
• Red Vitamin
• Animal products (meat and dairy products)
provide the only dietary source of Vit.B12 for
humans.
• RDA - 0.5 mcg/day

5. Cobalamin (Cbl) absorption.

6. Vitamin B12
• Adequate absorption of cobalamin depends
upon five factors:
1. Adequate dietary intake
2. Acid-pepsin in the stomach
3. Pancreatic proteases
4. Gastric secretion of a functional intrinsic
factor
5. An ileum with functioning B12-IF receptors

7. Vitamin B12 deficiency
• Inadequate Vitamin B12 Intake
• Impaired Intestinal Absorption
-regional enteritis, neonatal necrotizing
enterocolitis, or celiac disease
-Bacterial overgrowth
-fish tapeworm – D.latum
-Surgical removal of terminal ileum
• Imerslund-Grasbeck syndrome - defects in
amnionless (AMN) or cubilin (CUBN) genes

8. Rare causes…
Pernicious anemia is extremely rare in children
younger than 10 years.
•
•
•
•
•
Congenital IF deficiency
Gastric surgery
Pancreatic insufficiency
Hereditary orotic aciduria
Thiamine responsive megaloblastic anemia

9. Folic Acid
• Occurs in animal products and in leafy
vegetables in the polyglutamate form
• RDA – 50-150 mcg/day

10. Folic Acid deficiency
• Inadequate folate Intake
• Increased requirements (infancy and early
childhood, chronic hemolysis, infections)
• Goat’s milk
• Decreased Folate Absorption
-chronic diarrheal states or diffuse inflammatory
disease
• Drug induced:anticonvulsant drugs
(e.g., phenytoin, primidone, phenobarbital)
, methotrexate, pyrimethamine, trmethoprim

11. Clinical Manifestations
• Anemia, anorexia, irritability, easy fatigability
• Hyperpigmentation of knuckles and terminal
phalanges.
• Neurologic signs may precede onset of anemia
– loss of position and vibration sense (earliest)

12. Investigations - Hemogram
• Macrocytic RBCs (MCV >110 fl) and cytopenias
• Hypersegmented neutrophils

13. Folate levels
• Serum folate levels are primarily a reflection
of short-term folate balance
• serum folate - >4 ng/mL : folate deficiency is
effectively ruled out.
• serum folate <2 ng/mL : diagnostic of folate
deficiency
• Red cell folate concentration is theoretically a
more reliable indicator of tissue folate
adequacy

14. Cobalamin levels
• >300 pg/mL — normal result; Cbl deficiency is
unlikely
• 200 to 300 pg/mL— borderline result; Cbl
deficiency possible.
• <200 pg/mL— low; consistent with Cbl
deficiency (specificity of 95 to 100 percent)

15. Schilling test

16. Schilling test
Test
Gastrectomy,
pernicious
anemia
Celiac disease*
Bacterial
overgrowth
Ileal resection
or disease•
Pancreatic
insufficiency
Vitamin B12
Low
Low
Low
Low/normal
Low
Vitamin B12 +
intrinsic factor
Normal
Low
Low
Low/normal
Low
Vitamin B12 +
antibiotics
n/a
Low
Normal
Low/normal
Low
Vitamin B12 +
gluten-free diet
n/a
Normal
n/a
Low/normal
Low
Vitamin B12 +
pancreatic
enzymes
n/a
n/a
n/a
n/a
Normal

17. Bone Marrow Examination
• Erythroid hyperplasia; Nuclear – cytoplasmic
asynchrony
• Granulocytic precursors - giant
metamyelocytes and band forms

18. Treatment
• Cobalamin deficiency – Parenteral (i.m) – 1000 mcg
daily for 1 week, weekly for next 4 weeks (until
hematocrit becomes normal)
• Pernicious anemia and malabsorption – Monthly
cobalamin supplementation.
• Erratic absorption with oral formulations
• Folate deficiency - folic acid(1 to 5 mg/day orally) for
3 – 4 weeks