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Megaloblastic anemia in childhood

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A comprehensive approach to diagnosis and management of Megaloblastic anemia in children

A comprehensive approach to diagnosis and management of Megaloblastic anemia in children

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  • 1. Megaloblastic Anemia Dr.Singaram.A
  • 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