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Holo-transcobalamin (holoTC), the biologically active form of vitamin B 12 in blood, also has a wide window with indeterminate levels,36 and the reference values strongly depend on the assay method.37 Measuring serum concentrations of MMA and homocysteine may be helpful in establishing B 12 deficiency, especially in people with borderline serum B 12 levels, ie, those between 148 and 300 pmol/L.363839 However, MMA was normal in 52% of individuals with holoTC concentrations below 20 pmol/L, the latter being indicative of deficiency.40 Additionally, specific genetic polymorphisms41 and recent treatment with antibiotics may result in false normal MMA levels,42 and MMA is also elevated with impaired renal function.43 Serum homocysteine is less specific for B 12 deficiency, and can also be elevated in folate deficiency, vitamin B 6 deficiency, vitamin B 2 deficiency, and impaired renal function, hypothyroidism, and by certain medications.44 Additionally, in patients who are already taking some form of oral B 12 supplementation, demonstrating B 12 deficiency can be a challenge, even when symptoms are typical (including those of neuropathy-like paraesthesia and numbness) as serum B 12 concentrations may be just within, or sometimes above, the normal range.26 Serum B 12 , homocysteine, and methylmalonic acid (MMA) levels (box 2) are unreliable predictors of B 12 responsive neuropathy (neurological disorders that respond to B 12 supplementation).454647 In these situations, expert opinion suggests that clinicians consider discussing with their patients a therapeutic trial of B 12 injections.71147 How is B 12 deficiency treated

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