What provokes megaloblastic anemias?

The following causes of megaloblastic anemia development are identified.

Vitamin B ₁₂ deficiency:

Nutritional deficiency (dietary vitamin B12 content _< 2 mg/day; maternal vitamin B12 deficiency leading to reduced vitamin B12 content _inbreast milk);

_{Vitamin B12} absorption disorders:

• intrinsic factor (Castle factor) deficiency:
  • pernicious anemia;
  • stomach surgery:
  • total gastrectomy;
  • partial gastrectomy;
  • gastric bypass;
  • action of caustic substances;
• functional anomaly of intrinsic factor;
• biological competition:
  • small intestinal bacterial overgrowth;
  • anastomoses and fistulas;
  • blind loops and pockets;
  • strictures;
  • scleroderma;
  • achlorhydria;
  • helminths (Diphylobothrium latum);
• malabsorption in the ileum:
  • familial selective malabsorption of vitamin B12 ₍ Imerslund-Graesbeck syndrome);
  • drug-induced malabsorption of vitamin B ₁₂;
  • chronic diseases of the pancreas;
  • Zollinger-Ellison syndrome;
  • hemodialysis;
  • diseases affecting the ileum:
  • ileal resection and bypass;
  • local enteritis;
  • celiac disease;

_{Vitamin B12} transport disorders:

• hereditary transcobalamin II deficiency;
• transient transcobalamin II deficiency;
• partial transcobalamin I deficiency;

_{Vitamin B12} metabolism disorders:

• hereditary:
  • adenosylcobalamin deficiency;
  • methylmalonyl-CoA mutase deficiency (muf, mut);
  • combined methylcobalamin and adenosylcobalamin deficiency;
  • methylcobalamin deficiency;
• acquired:
  • liver disease;
  • protein deficiency (kwashiorkor, marasmus);
  • drug-induced (eg, aminosalicylic acid, colchicine, neomycin, ethanol, oral contraceptives, metformin).

Folate deficiency:

• nutritional deficiency;
• increased need:
  • alcoholism and liver cirrhosis;
  • pregnancy;
  • newborns;
  • diseases associated with increased cell proliferation;
• congenital malabsorption of folic acid;
• drug-induced folate malabsorption;
• extensive bowel resection, jejunal resection.

Combined deficiency of folate and vitamin B ₁₂:

• tropical spruce;
• gluten-dependent enteropathy.

Congenital disorders of DNA synthesis:

• orotic aciduria;
• Lesch-Nyhan syndrome;
• thiamine-dependent megaloblastic anemia;
• deficiency of enzymes necessary for the metabolism of folic acid:
  • N5-methyl-tetrahydrofolate transferase;
  • formiminotransferases;
  • dihydrofolate reductase;
• transcobalamin II deficiency;
• abnormal transcobalamin II;
• homocystinuria and methylmalonic aciduria.

Drug and toxin-induced disorders of DNA synthesis:

• folate antagonists (methotrexate);
• purine analogues (mercaptopurine, azathioprine, thioguanine);
• pyrimidine analogs (fluorouracil, 6-azauridine);
• ribonucleotide reductase inhibitors (cytosine arabinoside, hydroxyurea);
• alkylating agents (cyclophosphamide);
• nitric oxide;
• arsenic;
• chloroethane.

In addition, megaloblastic anemia can be caused by erythroleukemia.