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Dtsch Arztebl Int. 2008 Oct;105(40):680-5. doi: 10.3238/arztebl.2008.0680. Epub 2008 Oct 3.

Causes and early diagnosis of vitamin B12 deficiency.

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Universitätsklinikum des Saarlandes, Klinische Chemie und Laboratoriumsmedizin/Zentrallabor, Homburg/Saar.



Vitamin B(12) deficiency is widespread. Among the population groups at risk are older people, vegetarians, pregnant women, and patients with renal or intestinal diseases. The neurological symptoms of vitamin B(12) deficiency are unspecific and can be irreversible. Early detection is therefore important, using the most sensitive and specific markers available.


Selective literature review.


Total serum vitamin B(12) is a late, relatively insensitive and unspecific biomarker of deficiency. Holotranscobalamin (holoTC), also known as active B(12), is the earliest laboratory parameter for B(12) deficiency, while methyl malonic acid (MMA) is a functional B(12) marker that will increase when the B(12) stores are depleted. Isolated lowering of holoTC shows B(12) depletion (negative B(12) balance), while lowered holoTC plus elevated MMA and homocysteine indicates a metabolically manifest B(12) deficiency, although there still may be no clinical symptoms. The diagnostic use of holoTC allows treatment to be instituted before irreversible neurological damage occurs. As the first clinical manifestations of vitamin B(12) deficiency are unspecific, those at risk should have their B(12) status checked regularly, every two to three years. Because no randomized controlled trials have yet been completed, the diagnostic and therapeutic measures proposed here are merely recommendations.


diagnosis; homocysteine; neurological diagnosis; treatment concept; vitamin B12

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