Cobalamin vitamin deficiency

Strict vegetarian diet or after diseases affecting cobalamin absorption. The main effects of vitamin deficiency are pernicious anemia, macrocytosis, and neurological problems. A particularity of this vitamin is that it can be stored especially in the liver and kidneys. 

The answer is D. Several vitamin deficiencies can cause anemia due to reduced DNA synthesis in the erythropoietic cells of the bone marrow, especially folic acid and vitamin Bj2 (cobalamin), which are particularly prevalent among elderly patients due to poor diet and reduced absorption. In addition, deficiencies of either folic acid or vitamin Bj2 could produce the megaloblastic anemia seen in this patient. However, the absence of neurologic symptoms, a hallmark of vitamin Bj2 deficiency, makes that diagnosis less likely than folic acid deficiency. 

The human body contains only about 1.5 mg of cobalt, almost all of it is in the form of cobalamin, vitamin B12. Ruminant animals, such as cattle and sheep, have a relatively high nutritional need for cobalt and in regions with a low soil cobalt content, such as Australia, cobalt deficiency in these animals is a serious problem. This need for cobalt largely reflects the high requirement of the microorganisms of the rumen (paunch) for vitamin B12. All bacteria require vitamin B12 but not all are able to synthesize it. For example, E. coli lacks one enzyme in the biosynthetic... 

RH Allen, SP Stabler, DG Savage, J Lindenbaum. Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J 7 1344-1353, 1993. 

There is reason to conclude that vitamin deficiency might contribute to arteriosclerosis. There is a correlation between elevated homocysteine levels and incidence of cardiovascular disease (59). There is debate as to whether homocysteine contributesto the dam e of cells on the interior of blood vessel or whether homocysteine is a marker of intensive cell repair and formation of replacement cells. Nevertheless, administration of pyridoxine, folic acid, and (yanocobalamin are being recommended along with the two antioxidant vitamins, a-tocopherol and ascorbic acid for arteriosclerosis. Vitamin Bg is required for two of the steps in the catabolism of homocysteine to succinyl CoA (Fig. 8.52). Note in Fig. 8.52 (bottom) that biotin and a coenzyme form of cobalamin also are required for... 

Cobalmin Deficiency. Pernicious anemia is the disease associated with vitamin Bi2 deficiency. It is usually caused by the inability to produce intrinsic factor. Indeed, many times the vitamin must be administered by injection. The blood picture, a megaloblastic anemia, is indistinguishable from that caused by folic acid deficiency. Indeed folic acid supplements can mask the blood picture. This is illustrated in Fig. 8.53. Removal of ad-enosyl cobalamin eliminates the regeneration of tetrahydrofolate during the methylation of homocysteine to methionine. Folic acid supplements provide a fresh source of tetrahydrofolate coenzymes. DNA synthesis can continue and new erythrocytes form. Excess folic acid also may compete for the available vitamin, further exacerbating vitamin deficiency. 

Deficiencies of methionine adenosyltransferase, cystathionine 8-synthase, and cystathionine )/-lyase have been described. The first leads to hypermethioninemia but no other clinical abnormality. The second leads to hypermethioninemia, hyperhomocysteinemia, and homo-cystinuria. The disorder is transmitted as an autosomal recessive trait. Its clinical manifestations may include skeletal abnormalities, mental retardation, ectopia lentis (lens dislocation), malar flush, and susceptibility to arterial and venous thromboembolism. Some patients show reduction in plasma methionine and homocysteine concentrations and in urinary homocysteine excretion after large doses of pyridoxine. Homocystinuria can also result from a deficiency of cobalamin (vitamin B12) or folate metabolism. The third, an autosomal recessive trait, leads to cystathioninuria and no other characteristic clinical abnormality. 

Methyl trap The sequestering of tetrahydrofolate as N -methyl THF because of decreased conversion of homocysteine to methionine as a result of a deficiency of methionine synthase or its cofactor, cobalamin (vitamin B ). 

Cobalamin (vitamin Bj ) deficiency Inadequate uptake of cobalamin from the diet often due to lack of intrinsic factor an intestinal transport protein or less often due to unaugmented vegetarian diet that strictly avoids meat or meat products, the source of dietary cobalamin. 

Jean Ann Tonich developed a folate deficiency and is on the verge of devel-j oping a cobalamin (vitamin B12) deficiency as a consequence of prolonged moderately severe malnutrition related to chronic alcoholism. Before folate therapy is started, the physician must ascertain that the megaloblastic anemia is not caused by a pure B12 deficiency or a combined deficiency of folate and B12. 

The conversion of A -methyltetrahydrofolate to methyltetrahydrofolate requires adequate supplies of cobalamin (vitamin Bj ). In vitamin deficiency, A -methyltetrahydrofolate accumulates, whereas supplies of dihydrofolate, tetrahydrofolate, and dTMP are depleted. The answer is (D). 

The criteria for the diagnosis of vitamin deficiency are specific for every single vitamin. However, some common rules can be applied to most of the B vitamins. First, it has to be stated that, in clinical practice, some vitamins (biotin, pantothenic acid, niacin) are hardly ever measured and therefore data on vitamin status are hardly available. Other vitamins like folate and cobalamin are measured regularly using commercial assays. 

Since concentration measurements in blood may not reflect true vitamin status, the measurement of metabolites or activity of enzymes that use a coenzyme form of a B vitamin has been suggested. For example, the measurement of either homocysteine or methylmalonic acid has been suggested as a marker for cobalamin status, and the erythrocyte transaminase coefficient has been suggested as a marker for vitamin Bg status. However, there are no accepted definitions for the diagnosis of vitamin deficiency in the case of many vitamins. 

Vitamins Bg, B12 and folate have specific and vital functions in the metabolism a deficiency (or excess) causes specific diseases such as hyperlipidemia, hypertension, obesity or cardiovascular diseases, which are related to a modern lifestyle and common in industrialized countries. As observed in several studies, cobalamin (B12) deficiency in most cases coincides with an insufficient folate status (Ball 2006 Howard et al. 1998 Morris et al. 2007). 

Carmel, R., 2008. How I treat cobalamin (vitamin B12) deficiency. Blood. 112 2214-2221. 

Prevalence of subclinical cobalamin deficiency is higher than previously expected, especially where in asymptomatic subjects are apparently healthy but at risk of developing vitamin deficiency due to physiopathological conditions and/or lifestyle. 

Dietary deficiency in the absence of absorption defects can be effectively reversed with oral supplementation of 1 p.m of vitamin B 2 daily. If deficiency is related to a defect in vitamin absorption, daily doses of 1 pg adininistered subcutaneously or intramuscularly are effective (33). However, a single intramuscular dose of 100 pg of cobalamin once per month is adequate in patients with chronic gastric or ileal damage. Larger doses are generally rapidly cleared from the plasma into the urine and are not effective unless the patient demonstrates poor vitamin retention. 

Methionine synthase deficiency (cobalamin-E disease) produces homocystinuria without methylmalonic aciduria 677 Cobalamin-c disease remethylation of homocysteine to methionine also requires an activated form of vitamin B12 677 Hereditary folate malabsorption presents with megaloblastic anemia, seizures and neurological deterioration 678... 

Cobalamin-c disease remethylation of homocysteine to methionine also requires an activated form of vitamin B12. In the absence of normal B12 activation, homocystinuria results from a failure of normal vitamin B12 metabolism. Complementation analysis classifies defects in vitamin B12 metabolism into three groups cblC (most common), cblD and cblF. Most individuals become ill in the first few months or weeks of life with hypotonia, lethargy and growth failure. Optic atrophy and retinal changes can occur. Methylmalonate excretion is excessive, but less than in methylmalonyl-CoA mutase deficiency, and without ketoaciduria or metabolic acidosis. 

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