A 37-year-old man comes to the emergency department due to worsening fatigue and a prolonged history of abdominal pain. He has had no surgeries and takes no medications. Examination shows mucosal pallor and epigastric tenderness on deep palpation. Blood samples are obtained for testing. Laboratory results are as follows:
| Hemoglobin | 8.2 g/dL |
| Mean corpuscular volume | 110 µm3 |
| Folate | 10 ng/mL (normal: 2.5-20) |
| Vitamin B12 | 90 pg/mL (normal: 200-800) |
| Gastrin | 168 pg/mL (normal: 0-180) |
| Intrinsic factor–blocking antibody | negative |
CT scan of the abdomen reveals atrophy of the pancreas with multiple calcifications. A primary impairment in which of the following steps of cobalamin absorption is the most likely cause of this patient's anemia?
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This patient with a prolonged history of epigastric abdominal pain has developed fatigue due to anemia from vitamin B12 (ie cobalamin) deficiency. This history, combined with imaging findings of pancreatic atrophy and calcifications, is consistent with chronic pancreatitis, a progressive inflammatory disease that ultimately leads to pancreatic fibrosis.
In chronic pancreatitis, acinar cell destruction leads to decreased secretion of pancreatic proteolytic enzymes (eg, exocrine insufficiency). This not only affects protein and fat absorption, which can cause weight loss and steatorrhea, but also may lead to vitamin B12 deficiency. Pancreatic proteolytic enzymes are needed to release vitamin B12 from the vitamin B12–R protein complex (R protein is also known as transcobalamin I or haptocorrin), a necessary step that enables vitamin B12 to bind intrinsic factor, which ultimately facilitates terminal ileal absorption. Chronic pancreatitis may also lead to islet cell destruction and cause diabetes mellitus (eg, endocrine insufficiency).
(Choice A) Long-term use of a proton pump inhibitor (PPI) may cause vitamin B12 deficiency due to the inhibition of gastric acid secretion, which is needed to release vitamin B12 from animal proteins. This patient does not use a PPI; furthermore, hypergastrinemia (ie, elevated serum gastrin) is expected in the setting of decreased gastric acid secretion.
(Choice B) Transcobalamin II is a carrier protein that transports vitamin B12 in the circulation after terminal ileal absorption. Transcobalamin II deficiency is a rare genetic condition that presents in infancy with failure to thrive and megaloblastic anemia.
(Choice D) Pernicious anemia is an autoimmune condition that causes parietal cell destruction, decreased intrinsic factor production, and vitamin B12 deficiency. Hypergastrinemia is expected because parietal cell destruction leads to decreased gastric acid secretion. This patient is also younger than most individuals with pernicious anemia, which is usually diagnosed later in life (median age 70-80).
Educational objective:
Chronic pancreatitis may cause vitamin B12 deficiency due to decreased production of pancreatic proteolytic enzymes (eg, exocrine insufficiency), which are needed to release vitamin B12 from R protein. Other manifestations of chronic pancreatitis include chronic epigastric pain, weight loss, and steatorrhea.