A 15-year-old boy is brought to the clinic for a follow-up appointment. Since early childhood, the boy has had recurrent episodes of pancreatitis requiring hospitalization. The patient has not been hospitalized since before his last follow-up appointment a few months ago. However, he has been feeling more tired recently and states he has not been taking his prescribed medications. Family history is notable for recurrent pancreatitis in a sibling. Neurologic examination shows hyporeflexia and decreased proprioception in the lower extremities. Laboratory studies show mild hemolytic anemia. This patient's presentation is most likely due to a deficiency of which of the following?
Fat-soluble vitamin deficiency | |
Vitamin | Clinical features |
Vitamin A |
|
Vitamin D |
|
Vitamin E |
|
Vitamin K |
|
Patients with recurrent pancreatitis (eg, hereditary, cystic fibrosis) are at risk for exocrine pancreatic insufficiency, or decreased secretion of pancreatic enzymes that are involved in the digestion of fat (most important), carbohydrates, and protein. Without enzyme replacement (eg, lipase), patients often develop chronic fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, and K). In this case, the patient's neurologic and hematologic findings are most consistent with vitamin E deficiency.
Vitamin E primarily serves as a free radical scavenger to protect fatty acids from oxidation; deficiency predisposes cell membranes to oxidative injury. The cells that are most susceptible include neurons with long axons (due to large membrane surface area) and erythrocytes (due to high oxygen exposure). Therefore, the most common clinical manifestations of vitamin E deficiency are:
Neuromuscular disease: Involvement of the dorsal column in the spinal cord is associated with the loss of proprioception and vibratory sense. Spinocerebellar tract degeneration causes ataxia, and peripheral nerve dysfunction results in motor and sensory loss and hyporeflexia. Skeletal myopathy can also contribute to muscle weakness.
Hemolysis: Erythrocyte fragility and a shortened red blood cell lifespan result in hemolytic anemia, which can present with fatigue, as seen in this patient.
(Choices A, B, and C) Niacin (vitamin B3), riboflavin (vitamin B2), and thiamine (vitamin B1) are water soluble and unaffected by fat malabsorption, making deficiency unlikely in this patient who has risk factors for exocrine pancreatic insufficiency. Moreover, the clinical findings of these vitamin deficiencies are inconsistent with this patient's presentation: Niacin deficiency causes pellagra (eg, dermatitis, diarrhea, dementia), riboflavin deficiency manifests with a normocytic anemia and mucosal changes (eg, stomatitis, cheilitis, glossitis), and thiamine deficiency is characterized by beriberi and Wernicke-Korsakoff syndrome.
(Choice D) In contrast to this patient's presentation, vitamin A deficiency manifests with night blindness, dry eyes (xerophthalmia), and hyperkeratosis (thickened, dry skin).
(Choice F) Vitamin K is necessary for hepatic synthesis of clotting factors II, VII, IX, and X. Deficiency presents with easy bleeding and bruising, not seen in this patient.
Educational objective:
Vitamin E is a fat-soluble vitamin, and deficiency can occur in individuals with fat malabsorption due to recurrent pancreatitis. Vitamin E deficiency is associated with increased susceptibility of the neuronal and erythrocyte membranes to oxidative stress. Clinical manifestations include decreased proprioception, ataxia, peripheral neuropathy (eg, hyporeflexia), and hemolytic anemia.