A 54-year-old woman is evaluated in the clinic for exertional dyspnea and easy fatigability. The patient has no chest pain, cough, or wheezing. She does not use tobacco, alcohol, or illicit drugs. On physical examination, her gait is unstable when her eyes are closed and there is impaired vibratory sensation in the lower extremities. Marked pallor of the conjunctivae, nail beds, and palms is present. Which of the following laboratory tests would help confirm the most likely diagnosis in this patient?

Question

A 54-year-old woman is evaluated in the clinic for exertional dyspnea and easy fatigability.  The patient has no chest pain, cough, or wheezing.  She does not use tobacco, alcohol, or illicit drugs.  On physical examination, her gait is unstable when her eyes are closed and there is impaired vibratory sensation in the lower extremities.  Marked pallor of the conjunctivae, nail beds, and palms is present.  Which of the following laboratory tests would help confirm the most likely diagnosis in this patient?

Quizplus · Accepted Answer

11ec160b_36d7_8da0_9249_a76452d60ba3_MD0001_00 This patient has features of anemia (eg, exertional dyspnea, fatigue, pallor) with associated neurologic deficits that are highly suggestive of vitamin B₁₂ deficiency. The hematologic manifestations of B₁₂ deficiency (eg, megaloblastic anemia, pancytopenia) are related to impaired DNA synthesis. Vitamin B₁₂ (hydroxocobalamin) also serves as a cofactor for methylmalonyl-CoA mutase (converts methylmalonyl-CoA to succinyl-CoA) and methionine synthase (converts homocysteine and folic acid to methionine). B₁₂ deficiency consequently results in elevated levels of serum methylmalonic acid and homocysteine. Increased methylmalonic acid levels can disrupt myelin synthesis and result in subacute combined degeneration of the dorsal columns (eg, loss of proprioception/vibration, Romberg sign) and lateral corticospinal tract (eg, spastic muscle weakness, hyperreflexia). Axonal degeneration of peripheral nerves can also be seen. (Choice A) Glucose-6-phosphate dehydrogenase deficiency (G6PD) leads to acute hemolytic anemia in response to oxidative stress. Neurologic manifestations are not present in G6PD-associated anemia. (Choice B) Erythrocyte glutathione reductase activity may be decreased in patients with vitamin B₂ (riboflavin) deficiency because glutathione reductase uses bound FAD (derived from vitamin B₂) and NADPH as cofactors to reduce disulfide bonds. Vitamin B₂ deficiency typically presents with normocytic anemia and inflammation of the lips (cheilosis), mouth (stomatitis), and/or tongue (glossitis). (Choice C) Pyruvate kinase generates ATP through the conversion of phosphoenolpyruvate to pyruvate. Pyruvate kinase deficiency is an autosomal recessive condition that typically presents with congenital hemolytic anemia due to impaired glycolytic ATP generation. (Choice D) Transketolase is an enzyme of the hexose monophosphate pathway that utilizes thiamine (vitamin B₁) as a coenzyme. Erythrocyte transketolase activity is decreased in thiamine deficiency, which causes Wernicke-Korsakoff syndrome and beriberi. (Choice F) Serum protoporphyrin levels are increased in iron deficiency anemia, lead poisoning, and erythropoietic protoporphyria. Lead poisoning can cause sideroblastic anemia and peripheral neuropathy, but other characteristic features (eg, abdominal/musculoskeletal pain, cognitive impairment, nephropathy) are not evident in this patient. Educational objective: Vitamin B₁₂ deficiency often presents with megaloblastic anemia (impaired DNA synthesis) and neurologic deficits (impaired myelin synthesis). Characteristic neurologic findings include subacute combined degeneration of the dorsal columns and lateral corticospinal tract. Elevations in methylmalonic acid and homocysteine levels occur due to decreased metabolism of these molecules. __________ References: Clinical practice. Vitamin B12 deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/23301732)

A 54-Year-Old Woman Is Evaluated in the Clinic for Exertional