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Decreased levels of norepinephrine, serotonin, and dopamine
23%
6/26
Family history of Fanconi anemia
65%
17/26
Increased levels of serum methylmalonic acid
4%
1/26
Mammillary body damage
Senile plaques and neurofibrillary tangles
0%
0/26
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This patient who presents with fatigue, neurologic symptoms (loss in vibratory sensation, a positive Babinski sign, and ataxia), and macrocytic, megaloblastic anemia most likely has vitamin B12 deficiency. Unlike folate deficiency, vitamin B12 deficiency is associated with increased levels of serum methylmalonic acid. Vitamin B12 (cobalamin) is a water-soluble vitamin found only in animal products and, unlike other water-soluble vitamins, is stored in the liver. The elderly, vegans, and patients with alcohol use disorder are at an increased risk of vitamin B12 deficiency. This disease presents with chronic fatigue and pallor due to a macrocytic, megaloblastic anemia with hypersegmented neutrophils. Patients will also have neurological symptoms such as neuropathy, dementia, and loss of vibratory sensation if the deficiency persists. Vitamin B12 deficiency is associated with elevated homocysteine and methylmalonic acid levels. Treatment involves either monthly B12 injections or high-dose oral supplements. Figure/Illustration A shows a peripheral blood smear with a hypersegmented neutrophil (red circle). These neutrophils are seen in patients with macrocytic, megaloblastic anemias such as vitamin B12 deficiency. Pavlov et al. studied the mechanisms by which vitamin B12 deficiency leads to neurologic symptoms. They discuss how the spectrum of neurologic symptoms includes subacute combined degeneration of the spinal cord, sensorimotor polyneuropathy, optic nerve neuropathy, and cognitive disorders. They recommend analyzing transcobalamin levels to understand whether a patient is vitamin deficient in difficult cases. Incorrect Answers: Answer 1: Decreased levels of norepinephrine, serotonin, and dopamine are associated with major depressive disorder (MDD). Symptoms include sleep disturbance, anhedonia, guilt, loss of energy, loss of concentration, appetite changes, psychomotor retardation/agitation, suicidal ideation, and depressed mood for at least 2 weeks. While MDD can also present as pseudodementia in the elderly, it does not explain the patient’s hematologic abnormalities. Answer 2: A family history of Fanconi anemia can increase one’s risk of myelodysplastic syndrome (MDS), a defect in cell maturation of all non-lymphoid lineages. MDS is associated with accelerated erythropoiesis causing an increase in reticulocytes and an increased MCV without megaloblasts. MDS would not explain the neurologic symptoms seen in this patient. Answer 4: Mammillary body damage is associated with Wernicke-Korsakoff syndrome due to thiamine (vitamin B1) deficiency which presents with ataxia, confusion, ophthalmoplegia, confabulation, memory loss, and personality changes/psychosis. Though thiamine deficiency is associated with alcohol use disorder and malnutrition, it does not present with macrocytic, megaloblastic anemia. Answer 5: Senile plaques and neurofibrillary tangles are associated with Alzheimer disease. Alzheimer disease presents as short-term memory loss that gradually progresses to behavior/personality changes, disorientation, and long-term memory loss. It is not associated with hematologic abnormalities. Bullet Summary: Vitamin B12 deficiency presents with megaloblastic anemia and neurological symptoms with an increase in methylmalonic acid and homocysteine levels.
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