A 7 LJ-year-old female presen ts for evaluation of chronic and progressive fatigue and weakness. She lives with two cats and a German Shepherd dog. Patien t has a h istory of hypertension and hyperlipidemia with occasional gastroesophageal reflux symp-toms. Pa tient reports no prior surgical p rocedures . Urine analys is reveals no evi-dence of hematuria or hemoglobinuria. Stool is negative for occult blood . Laboratory evaluation reveals hemoglobin of LJ.2 g/d l, mean corpuscular volume (MCV) of 1 2 0 fl. leukocyte count of 2 , 1 00/JLL, platelet cou nt of LJ S, OOO/JLL, and an LDH level of LJ , 700 U/L. Peripheral blood smear is shown Which of the following is not among the possible explanations of the patient's presentation?

Further evaluation revealed vitamin Bl 2 level 292 pg/mL, serum folate 0.9 ng/mL, and RBC folate 24 ng/mL. Methylmalonic acid level was normal, while homocysteine was found to be elevated. What is the most likely diagnosis?
- Folic acid deficiency
- Vitamin B l2 deficiency
- Combined folic acid and vitamin Bl2 deficiency
A. Decreased levels of serum and RBC folate in conjunction with normal levels of methyl-malonic acid are consistent with the diagnosis of folic acid deficiency. Elevation of both methylmalonicacid and homocysteine can be used to detect cases of early vitamin Bl2 deficiency, as methylmalonic acid levels are normal in folic acid deficiency, while homocysteine is usually elevated. RBC folate levels are considered to be a better reflection of tissue folate stores compared with serum folate, which can fluctuate widely following meals. However, studies have shown that the information provided by both tests is comparable, and thus the more expensive RBC folate test is reserved for cases of high suspicion for folate deficiency despite normal serum folate levels. The m�thylfolate trap hypothesis predicts higher serum folate levels in conjunction with lower RBC folate levels associated with vitamin Bl2 deficiency, as reduced methionine synthase activity causes reduced intracellular methylfolate metabo-lism and slow cellular loss by diffusion into the circulation. However, this hypothesis has never been definitely demonstrated in humans (J Clin Pathol. 2003;56(12):924, Br J Haematol. 2006;1 32(5):623).
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