| 1. Is the deficiency likely to relapse? Must cobalamin replacement be lifelong, long term, or short term?* |
| 2. If the deficiency is only subclinical when first diagnosed, is the deficiency likely to remain clinically silent or to progress to more serious deficiency?† |
| 3. Should cobalamin replacement be done with periodic injection or large daily oral doses, or will small oral doses suffice? |
| 4. Are all sources of oral cobalamin, or only food-bound cobalamin, absorbed poorly? Should supplements be taken on an empty stomach?‡ |
| 5. Are additional nutrient deficiencies likely to coexist and should they be sought?§ |
| 6. Does the underlying disorder require direct treatment itself? Can it be reversed? |
| 7. Which cobalamin-unrelated complications of the underlying disease require independent action?‖ Do comorbidities or risks linked to the underlying disease exist? |
| 8. If cobalamin absorption is normal, is the cause of the cobalamin deficiency then dietary, nitrous oxide-related, or a genetic disorder of metabolism or transport? Could the diagnosis of cobalamin deficiency itself be mistaken? |
| 1. Is the deficiency likely to relapse? Must cobalamin replacement be lifelong, long term, or short term?* |
| 2. If the deficiency is only subclinical when first diagnosed, is the deficiency likely to remain clinically silent or to progress to more serious deficiency?† |
| 3. Should cobalamin replacement be done with periodic injection or large daily oral doses, or will small oral doses suffice? |
| 4. Are all sources of oral cobalamin, or only food-bound cobalamin, absorbed poorly? Should supplements be taken on an empty stomach?‡ |
| 5. Are additional nutrient deficiencies likely to coexist and should they be sought?§ |
| 6. Does the underlying disorder require direct treatment itself? Can it be reversed? |
| 7. Which cobalamin-unrelated complications of the underlying disease require independent action?‖ Do comorbidities or risks linked to the underlying disease exist? |
| 8. If cobalamin absorption is normal, is the cause of the cobalamin deficiency then dietary, nitrous oxide-related, or a genetic disorder of metabolism or transport? Could the diagnosis of cobalamin deficiency itself be mistaken? |
Data are modified and expanded from Carmel.37
PA is permanent and requires lifelong treatment. Some failures of intestinal uptake of IF may be treatable and even reversible. The course of FBCM is long, but it occasionally fluctuates.
Mild or subclinical deficiency cannot be deemed innocuous if the underlying cause is early PA or other IF-related malabsorption. In contrast, most clinically silent deficiency is nonmalabsorptive in origin and unlikely to progress, and thus it may not need treatment.
Patients with FBCM may need to take cobalamin supplements on an empty stomach to prevent their binding to food in vitro; 1000-μg oral doses appear necessary in many cases of FBCM, but it is not known whether giving such chronically high doses to others who do not need them can have undesirable effects.
For example, broader malabsorption of additional nutrients is likely if intestinal disease is the cause and is less likely or limited to iron if the malabsorption is gastric in origin.
The risks of gastric malignancy and thyroid dysfunction in patients with PA require active screening. Such risks do not occur with other disorders.