Anaemia cobalamins

Bellou A, Aimone-Gastin I, De Korwin JD, Bronowicki JP, Moneret-Vautrin A, Nicolas JP, et al Cobalamin deficiency with megaloblastic anaemia in one patient under long-term omeprazole therapy. J Intern Med 1996 240 161-164. 

There are many causes of the clinical condition referred to as anaemia. One particular type, whose cause can be traced to a genuine metabolic defect is megaloblastic anaemia and is due to a deficiency of the vitamins B12 (cobalamin) and/or folate. These vitamins are required for normal cell division in all tissues, but the rapid production of red cells makes them more susceptible to deficiency. In megaloblastic anaemia the blood haemoglobin concentration falls the synthesis of haem is not impaired. Examination of the blood reveals the appearance of larger then normal cells called macrocytes and megaloblasts are found in the bone marrow. 

Very small amounts of cobalamin are required each day (<5 i.g) and the diet normally provides plenty more than the minimum, so dietary B12 deficiency is uncommon, except in very strict vegetarians. Pernicious anaemia arises when a defect in the stomach results in too little secretion of a protein called intrinsic factor, without which, cobalamin cannot be absorbed in the ileum of the small intestine. 

It is the role of jV5-methyl THF which is key to understanding the involvement of cobalamin in megaloblastic anaemia. The metabolic requirement for N-methyl THF is to maintain a supply of the amino acid methionine, the precursor of S-adenosyl methionine (SAM), which is required for a number of methylation reactions. The transfer of the methyl group from jV5-methyl THF to homocysteine is cobalamin-dependent, so in B12 deficiency states, the production of SAM is reduced. Furthermore, the reaction which brings about the formation of Ns-methyl THF from N5,N10-methylene THF is irreversible and controlled by feedback inhibition by SAM. Thus, if B12 is unavailable, SAM concentration falls and Ah -methyl THF accumulates and THF cannot be re-formed. The accumulation of AT-methyl THF is sometimes referred to as the methyl trap because a functional deficiency of folate is created. 

Vitamin Bn deficiency Deficiency, although rare, results in two serious problems megaloblastic anaemia (which is identical to that caused by folate deficiency) and a specific neuropathy called Bi2-associated neuropathy or cobalamin-deficiency-associated neuropathy (previously called, subacute combined degeneration of the cord). A normal healthy adult can survive more than a decade without dietary vitamin B12 without any signs of deficiency since it is synthesised by microorganisms in the colon and then absorbed. However, pernicious anaemia develops fairly rapidly in patients who have a defective vitamin B12 absorption system due to a lack of intrinsic factor. It results in death in 3 days. Minot and Murphy discovered that giving patients liver, which contains the intrinsic factor, and which is lightly cooked to avoid denaturation, cured the anaemia. For this discovery they were awarded the Nobel Prize in Medicine in 1934. 

C9. Cooper, B. A., and Whitehead, V. M., Evidence that some patients with pernicious anaemia are not recognized by radiodilution assay for cobalamin in serum. N. Engl. J. Med. 299, 816-818 (1978). 

Vitamin B12, cobalamin or cyanocobaltamin, C63H88CoN14Oi4P, has the most complicated structure of the B vitamins. It contains one atom of cobalt in its molecule. It is required in minute amounts but without it the manufacture of proteins and red blood cells is affected. A diet which is deficient in liver, eggs, meat, fish or milk can lead to pernicious anaemia. Vegetarians are often advised to take vitamin B12 supplements. 

The initial dose in cobalamin deficiency anaemias, including uncomplicated pernicious anaemia, is hydroxocobalamin 1 mg i.m. every 2-3 days for 5 doses to induce remission and to replenish stores. Maintenance may be 1 mg every 3 months higher doses will not find binding sites and will be eliminated in the urine. Higher doses are justified during renal or peritoneal dialysis where hydroxy-cobalamin clearance is increased, and resultant raised plasma methylmalonic acid and homocysteine represent an independent risk factor for vascular events in these patients (see later). 

Deficiency of folic acid leads to a megaloblastic anaemia because it is necessary for the production of purines and pyrimidines, which are essential precursors of deoxyribonucleic acid (DNA). The megaloblastic marrow of cobalamin deficiency is due to interference with folic acid utilisation and the morphological changes of cobalamin deficiency can be reversed by folic acid. It is vital to realise that folic acid does not provide adequate treatment for pernicious anaemia. Nor does vitamin 3 2 provide adequate treatment for the megaloblastic anaemia of folic acid deficiency, although a partial response may occur because vitamin plays a role in folate metabolism. 

B,(Cobalamin) Pernicious anaemia Senim B,. full blood count... 

Megaloblastic anemia (pernicious anaemia) results from a deficiency of cobalamin and THF. 

Isolierung von kristalllsiertem Vitamin ("Anti-pernicious anaemia factor", Cyano-cobalamin) aus Leber. 

B12 deficiency causes deficient methionine synthase activity, which results in megaloblastic anaemia similar to folate deficiency. In pernicious anaemia the parietal cells of the stomach are destroyed by autoimmune attack and are unable to produce intrinsic factor (SOkDa glycoprotein), which is needed for the absorption of cobalamin in the Ueum. 

Cobalamin deficiency hallmarks anaemia, gastrointestinal problems and neurological symptoms... 

Cobalamin deficiency. Cobalamin deficiency is a common condition caused by an insufficient intake of cobalamin or an inability to absorb the vitamin. If left untreated, the condition may result in irreversible neurological damage and eventually death caused by a severe anaemia. Measurement of serum cobalamin is the most commonly employed test in order to confirm or rule out the presence of cobalamin deficiency. 

Cobalamin (vitamin B12) a water-soluble B vitamin, normally involved in the human body metabolism, affecting DNA synthesis and regulation, fatty acid synthesis and energy production. Supplied by animal food, its defieiency leads to macrocytic anaemia, decreased bone marrow cell production, neurological problems, as well as metabolic issues (methylmalonyl-CoA acidosis, hyperhomocysteinemia). 

B. Cobalamin Coenzyme in transfer of one-carbon fragments and metabolism of folic acid Pernicious anaemia = megaloblastic anaemia with degeneration of the spinal cord... 

Folacin deficiency may lead to glossitis, diarrhoea, depression and confusion. Deficiency anaemia may develop especially in pregnancy and in elderly people. Symptoms of deficiency are similar to symptoms of cobalamine deficiency (known as macrocytic anaemia). Megaloblastic anaemia, the most common cause of macrocytic anaemia, is due to a deficiency of either cobalamine or folic acid (or both). Deficiency in the early stages of pregnancy can lead to developmental defects of the foetus (spinal cord defects and incomplete development of the brain). Women who are at increased risk will need increased daily intake of folic acid. 

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