Vitamin B12 deficiency

Folate Deficiency

Common Causes of macrocytic anemia (MCV >100 fL)

1. Folate deficiency
2. Vit. B12 deficiency
3. Myelodysplastic syndromes
4. Acute myeloid leukemias
5. Drug-induced (e.g, hydroxyurea, zidovudine, chemotherapy agents such as 5-FU)
6. Liver disease
7. Alcohol abuse
8. Hypothyroidism

Orotic aciduria

Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase.

Autosomal recessive.

Presents in children as failure to thrive, developmental delay, and megaloblastic anemia refractory to folate and B12. No hyperammonemia (vs ornithine transcarbamylase deficiency— increased orotic acid with hyperammonemia).

Diagnosis: Orotic acid in urine.

Treatment:

uridine monophosphate or uridine triacetate to bypass mutated enzyme.