Pathophysiologic characteristics of disorders that cause cobalamin deficiency
| Characteristics and processes of cobalamin handling . | Loss of intrinsic factor (IF; ie, PA) . | Intestinal inability to absorb IF-bound cobalamin (eg, sprue) . | Impaired food-bound cobalamin absorption (eg, gastritis) . | Poor dietary intake of cobalamin (eg, veganism) . | Defective cellular metabolism or uptake (eg, chronic N2O toxicity) . |
|---|---|---|---|---|---|
| Cobalamin intake | Normal | Normal | Normal | Low | Normal |
| Absorption of free cobalamin | Very low* | Very low* | Normal* | Normal | Normal except in transcobalamin II deficiency |
| Absorption of food-bound cobalamin | Very low | Presumably very low | Low | Normal | Normal except in transcobalamin II deficiency |
| Daily losses of cobalamin† | Increased | Increased | Presumably normal | Normal | Presumably normal |
| Likelihood of deficiency to progress | Very high | Usually high, but varies with disorder | Usually low, but varies with disorder | Usually low but varies | Usually high |
| Progression time to biochemical deficiency | < 2-5 years‡ | < 2-5 years‡ | Several years‡§ | Several years‡§ | Undetermined in most cases but probably brief |
| Progression time to clinical deficiency | 2-5 years | 2-5 years but may vary | Many years to decades§ | Many years to decades§ | Days, weeks, or months, depending on disorder |
| Characteristics and processes of cobalamin handling . | Loss of intrinsic factor (IF; ie, PA) . | Intestinal inability to absorb IF-bound cobalamin (eg, sprue) . | Impaired food-bound cobalamin absorption (eg, gastritis) . | Poor dietary intake of cobalamin (eg, veganism) . | Defective cellular metabolism or uptake (eg, chronic N2O toxicity) . |
|---|---|---|---|---|---|
| Cobalamin intake | Normal | Normal | Normal | Low | Normal |
| Absorption of free cobalamin | Very low* | Very low* | Normal* | Normal | Normal except in transcobalamin II deficiency |
| Absorption of food-bound cobalamin | Very low | Presumably very low | Low | Normal | Normal except in transcobalamin II deficiency |
| Daily losses of cobalamin† | Increased | Increased | Presumably normal | Normal | Presumably normal |
| Likelihood of deficiency to progress | Very high | Usually high, but varies with disorder | Usually low, but varies with disorder | Usually low but varies | Usually high |
| Progression time to biochemical deficiency | < 2-5 years‡ | < 2-5 years‡ | Several years‡§ | Several years‡§ | Undetermined in most cases but probably brief |
| Progression time to clinical deficiency | 2-5 years | 2-5 years but may vary | Many years to decades§ | Many years to decades§ | Days, weeks, or months, depending on disorder |
Absorption of free cobalamin (cobalamin ingested free, as in crystalline supplements) depends on IF and its ileal uptake. The retention of normal ability to absorb free cobalamin differentiates food-bound cobalamin malabsorption from IF-based malabsorption (in which neither free nor food-bound cobalamin can be absorbed).
The largest source of daily losses is the portion of biliary cobalamin not reabsorbed by IF.
Systematic data are not available, but biochemical expression (appearance of cobalamin and metabolite abnormalities) can precede clinical expression by a year or more, presumably. The lag between biochemical and clinical expressions may be even greater in the more slowly progressive disorders.
Progression is slower than in IF-related malabsorption and may extend beyond a decade, but systematic data are lacking. More rapid progression may occur when other processes coexist.