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MKSAP: 57-year-old woman with decreased exercise tolerance

mksap
Conditions
August 16, 2014
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Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 57-year-old woman is evaluated for a 2-week history of decreased exercise tolerance and substernal chest pain on exertion. She also has an 8-month history of macrocytic anemia.

On physical examination, temperature is 36.7 °C (98.0 °F), blood pressure is 137/78 mm Hg, pulse rate is 104/min, and respiration rate is 17/min. BMI is 25. The patient has pale conjunctivae. Cardiopulmonary and neurologic examination findings are normal.

Initial laboratory studies indicate a hemoglobin level of 7.4 g/dL (74 g/L), a mean corpuscular volume of 104 fL, a serum vitamin B12 level in the low-normal range, and a normal red cell folate level. Subsequent testing indicates elevated serum homocysteine and methylmalonic acid levels.

An electrocardiogram is normal.

Which of the following is the most likely diagnosis?

A: Cobalamin deficiency
B: Combined folate and cobalamin deficiency
C: Folate deficiency
D: Transcobalamin II deficiency

MKSAP Answer and Critique

The correct answer is A: Cobalamin deficiency.

The most likely diagnosis is cobalamin (vitamin B12) deficiency. Patients with vitamin B12 deficiency have elevated homocysteine and methylmalonic acid levels, whereas patients with folate deficiency have only an elevated homocysteine level. In addition, an elevated methylmalonic acid level is more sensitive and specific for diagnosing vitamin B12 deficiency than a low serum vitamin B12 level because serum vitamin B12 levels do not adequately assess tissue vitamin B12 stores, especially in patients with vitamin B12 levels in the low-normal range. Consequently, homocysteine and methylmalonic acid should be measured in patients with suspected vitamin B12 deficiency. Similarly, red blood cell folate can be low in patients with folate or vitamin B12 deficiency. Because folate supplementation can correct the anemia of vitamin B12 deficiency but not the progression of neurologic defects, vitamin B12 deficiency must be excluded before supplemental folate is administered to a patient with macrocytic anemia and a low red cell folate level.

Patients with vitamin B12 deficiency have elevated homocysteine and methylmalonic acid levels, whereas patients with folate deficiency have only an elevated homocysteine level. Therefore, this patient does not have folate or combined folate-cobalamin deficiency.

Patients with transcobalamin II deficiency have normal serum vitamin B12 levels because transcobalamin II is the primary transporter protein for vitamin B12 entry into cells. Deficiency of transcobalamin II is quite rare and typically presents in childhood as a megaloblastic anemia with normal vitamin B12 and red cell folate levels.

Key Point

  • An elevated serum methylmalonic acid level is more sensitive and specific for diagnosing cobalamin (vitamin B12) deficiency than a low serum vitamin B12 level.

This content is excerpted from MKSAP 16 with permission from the American College of Physicians (ACP). Use is restricted in the same manner as that defined in the MKSAP 16 Digital license agreement. This material should never be used as a substitute for clinical judgment and does not represent an official position of ACP. All content is licensed to KevinMD.com on an “AS IS” basis without any warranty of any nature. The publisher, ACP, shall not be liable for any damage or loss of any kind arising out of or resulting from use of content, regardless of whether such liability is based in tort, contract or otherwise.

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