0521779407-07 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:10
578 Folic Acid/Cobalamin (Vitamin B12) Deficiencydifferential diagnosis
■Algorithm based on evidence for megaloblastic anemia or
neurologic-psychiatric manifestations c/w cobalamin deficiency
PLUS test results on serum cobalamin and serum folate
■If cobalamin >300 pg/ml and folate >4 ng/ml, cobalamin and folate
deficiency unlikely
■If cobalamin <200 pg/ml and folate >4 ng/ml, c/w cobalamin defi-
ciency
■If cobalamin 200–300 pg/ml and folate >4 ng/ml, cobalamin defi-
ciency still possible in∼15% (go to MMA+HCYS)
■If cobalamin >300 pg/ml and folate <2 ng/ml, c/w folate
deficiency
■If cobalamin <200 pg/ml and folate <2 ng/ml, c/w either combined
cobalamin plus folate deficiency or isolated folate deficiency (go to
MMA+HCYS)
■If cobalamin >300 pg/ml and folate 2–4 ng/ml, c/w either folate defi-
ciency or anemia unrelated to vitamin deficiency (go to MMA=
HCYS)
■Note: The test for RBC folate is insufficiently standardized and vali-
dated for clinical use; avoid.
■Interpretation Serum HCYS and Serum MMA tests
■Normal MMA=<270 nM; Normal HCYS=<14 mcM
■If both MMA+HCYS increased, c/w cobalamin deficiency or com-
bined cobalamin and folate deficiency
■If MMA normal but HCYS increased, folate deficiency likely
■If MMA and HCYS normal, cobalamin and folate deficiency excluded
■Schilling Test identifies locus for cobalamin malabsorption (then
further GI workup as indicated)
■Note: Delay test for >2 months after cobalamin replacement to
ensure normalization of intestinal morphology/function.
■Stage I test result, >8% of orally absorbed (crystalline) [57Co] cobal-
amin excreted in urine in 24 hours. In PA, <8% excreted.
■Stage II test (oral IF given with [57Co] cobalamin; if >8% is excreted,
result c/w PA; if <8% still excreted, proceed to stage III test – i.e.,
oral antibiotics using either amoxicillin-clavulanate (875 mg bid),
cephalexin (250 mg qid) plus metronidazole (250 mg tid), or nor-
floxacin 800 mg qd×10 days – and repeat stage I test. If >8% excre-
tion, result c/w bacterial usurpation; if still <8% excretion, cobalamin
malabsorption localized to ileal cause.
■Note: Patients with cobalamin deficiency from inability to break
down food protein-bound cobalamin (e.g., hypo/achlorhydria) have