Cobalamin Deficiency

Abstract

Cobalamin (Cbl, vitamin B12) consists of a corrinoid structure with cobalt in the centre of the molecule. Neither humans nor animals are able to synthesize this vitamin. Foods of animal source are the only natural source of cobalamin in human diet. There are only two enzymatic reactions in mammalian cells that require cobalamin as cofactor. Methylcobolamin is a cofactor for methionine synthase. The enzyme methylmalonyl-CoA-mutase requires adenosylcobalamin as a cofactor. Therefore, serum concentrations of homocysteine (tHcy) and methylmalonic acid (MMA) will increase in cobalamin deficiency. The cobalamin absorption from diet is a complex process that involves different proteins: haptocorrin, intrinsic factor and transcobalamin (TC). Cobalamin that is bound to TC is called holotranscobalamin (holoTC) which is the metabolically active vitamin B12 fraction. HoloTC consists 6 and 20% of total cobalamin whereas 80% of total serum cobalamin is bound to another binding protein, haptocorrin. Cobalamin deficiency is common worldwide. Cobalamin malabsorption is common in elderly subjects which might explain low vitamin status. Subjects who ingest low amount of cobalamin like vegetarians develop vitamin deficiency. No single parameter can be used to diagnose cobalamin deficiency. Total serum cobalamin is neither sensitive nor it is specific for cobalamin deficiency. This might explain why many deficient subjects would be overlooked by utilizing total cobalamin as status marker. Concentration of holotranscobalamin (holoTC) in serum is an earlier marker that becomes decreased before total serum cobalamin. Concentrations of MMA and tHcy increase in blood of cobalamin deficient subjects. Despite limitations of these markers in patients with renal dysfunction, concentrations of MMA and tHcy are useful functional markers of cobalamin status. The combined use of holoTC and MMA assays may better indicate cobalamin status than either of them. Because Cbl deficiency is a risk factor for neurodegenerative diseases an early diagnosis of a low B12 status is required which should be followed by an effective treatment in order to prevent irreversible damages.

Plasma homocysteine and vitamin B12 serum levels, red blood cell folate concentrations, C677T methylenetetrahydrofolate reductase gene mutation and risk of recurrent miscarriage: a case-control study in Spain

“…It could be argued that, as previously suggested [57,58] , serum measurement of bioactive vitamin B12 fraction holotranscobalamin (holoTC) and methylmalonic acid (MMA) would be better diagnostic tools defining vitamin B12 deficiency. While the value of these tests are acknowledged mainly in the research setting, in the routine clinical setting definite biomarker(s) of vitamin B12 status remain(s) to be established [32,59] .…”

Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer’s Disease

“…In Ireland, voluntary fortification as well as dietary supplements significantly contributed to achieving adequate folate intakes, but still, nearly 70% of women aged 18–50 years had suboptimal serum folate levels [190]. Vitamin B12 deficiency is typically seen as a problem of the elderly due to malabsorption [191,192,193,194]. However, Bailey and colleagues argue that even if the proportions of people with deficiencies in the general population are not very high, the absolute number of affected persons is still significant [186].…”

Rapid healing of a patient with dramatic subacute combined degeneration of spinal cord: a case report

“…Common reasons for cobalamin deficiencies can be divided into four groups (Table 1): diminished supply of cobalamin, disruption of cobalamin processing in the stomach (caused for instance by an autoimmune gastritis resulting from antibodies reacting with parietal cells leading to a decreased emission of intrinsic factor), intestinal resorption problems, and defective transport and intracellular metabolism [21, 23, 24]. …”