Megaloblastic Anemia

Dr.Singaram.A

Effect of cobalamin and folate on DNA synthesis

Actions of cobalamin

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

Cobalamin (Cbl) absorption.

Vitamin B12

• Adequate absorption of cobalamin depends upon five factors:

1. Adequate dietary intake2. Acid-pepsin in the stomach3. Pancreatic proteases4. Gastric secretion of a functional intrinsic

factor5. An ileum with functioning B12-IF receptors

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

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

Folic Acid

• Occurs in animal products and in leafy vegetables in the polyglutamate form

• RDA – 50-150 mcg/day

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

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)

Investigations - Hemogram

• Macrocytic RBCs (MCV >110 fl) and cytopenias

• Hypersegmented neutrophils

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

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)

Schilling test

Schilling test

TestGastrectomy,

pernicious anemia

Celiac disease*Bacterial

overgrowthIleal 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

Bone Marrow Examination

• Erythroid hyperplasia; Nuclear – cytoplasmic asynchrony

• Granulocytic precursors - giant metamyelocytes and band forms

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