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Query: UMLS:C0024523 (malabsorption)
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Several fundamental questions relating to the biochemical basis of megaloblastic hemopoiesis in vitamin B12 (B12) and folate deficiency and neurological damage in B12 deficiency remain to be answered. Among them is the explanation underlying (1) the failure of B12-deficient animals to develop megaloblastic hemopoiesis despite indirect evidence of impaired thymidylate synthesis and (2) the inverse relationship between the extent of hematologic and neurological damage in B12 deficiency. Diagnostic advances have led to the awareness that many patients with B12 or folate deficiency are hematologically normal and that subtle hematologic or neuropsychiatric manifestations may be found at a fairly early stage of developing B12 deficiency. Studies of the mechanism of absorption of B12 in food have identified the syndrome of food B12 malabsorption in which the degree of B12 deficiency is commonly, although not invariably, mild. Folate intake influences the prevalence of neural tube defects (NTDs) and a suboptimal folate status may be associated with an increased risk for dysplasia and cancer. The latter may be at least partly the result of uracil misincorporation into DNA and consequent DNA strand breaks. Folate status has also been linked to arteriosclerotic vascular disease through its effect on serum homocysteine levels. Uracil misincorporation into DNA and increased serum homocysteine levels may also be found in B12 deficiency. These adverse associations form the basis of a case for improving B12 or folate status in individuals with a mild degree of deficiency. Because inadequate folate intake is relatively common, especially in the elderly and the poor, the fortification of staple foods with folate is currently under active consideration.
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PMID:The wide spectrum and unresolved issues of megaloblastic anemia. 993 May 65

Folate or cobalamin deficiencies are usually detected by hematologic abnormalities, such as a macrocytic megaloblastic anemia, or often milder signs, such as hypersegmented neutrophils. In fact, these vitamin deficiencies may be associated with clinical conditions in which anemia and/or macrocytosis are absent, such as neuropsychiatric disorders and inborn errors of folate or cobalamin metabolism. A battery of sensitive tests, including blood vitamin levels, serum methylmaIonic acid and homocysteine assays, and the deoxyuridine suppression test in the bone marrow, allows for early detection of vitamin deficiency. Additional tests may be included to identify the causes of deficiency, such as the Schilling test using crystalline cyanocobalamin, or a modified Schilling test for showing food cobalamin malabsorption. Strategies for diagnosing a vitamin deficiency differ according to the hematologic and clinical presentations. The deleterious effects (aside from anemia) that arise from cobalamin or folate deficiency and include neurological complications, increased risk of vascular disease due to hyperhomocysteinemia, and increased risk of some types of cancer related to folate deficiency, underscore the importance of making an early diagnosis and instituting treatment with the appropriate vitamin in preventing permanent damage.
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PMID:Modern clinical testing strategies in cobalamin and folate deficiency. 993 May 67

Folate plays a key role in nucleic acid synthesis. As a consequence, the most conspicuous complication of folate deficiency or of derangements of folate metabolism is megaloblastic macrocytic anemia caused by interdiction of normal proliferation of rapidly dividing bone marrow cells. Other rapidly dividing cells, including those in the gastrointestinal tract, may also be affected by the megaloblastic process. This may result in malabsorption. However, there is mounting evidence to indicate that there are other earlier manifestations of folate deficiency or of longstanding suboptimal folate nutrition. Chief among these manifestations of folate deficiency are an increased predisposition to occlusive vascular disease and thrombosis, which have been linked to increased levels of homocysteine found in folate deficiency and abnormal states of folate metabolism. In addition, folate deficiency, previously considered free of neurological consequences, is now known to be associated with disturbances of mood, and even spinal cord syndromes similar to those seen in vitamin B12 deficiency. Finally, there is both experimental and clinical evidence to suggest that folate deficiency may interfere with immunologic status and may be associated with an increased predisposition to neoplasia. Nutritional as well as genetic factors may contribute to these various nonhematological manifestations of folate insufficiency.
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PMID:Folate deficiency beyond megaloblastic anemia: hyperhomocysteinemia and other manifestations of dysfunctional folate status. 993 May 68

Serum vitamin B12 levels are often low in human immunodeficiency virus (HIV)-infected patients. However, only a few patients appear to have actual vitamin B12 deficiency. A low red cell folate level accompanying the low vitamin B12 level makes the presence of vitamin B12 deficiency more likely. Our experience suggests that a low red cell folate level always indicates deficiency, but does not differentiate between vitamin B12 and folate deficiency. The deoxyuridine suppression test and the assay of serum or plasma total homocysteine and/or of methylmalonic acid levels can also be useful in the identification of patients with true vitamin B12 deficiency. HIV-positive patients frequently have absorption disorders, including vitamin B12 malabsorption. However, the correlation between vitamin B12 malabsorption and serum vitamin B12 and plasma homocysteine levels is poor. Abnormalities in vitamin B12-binding proteins, which are often found in HIV-positive patients, may explain many cases of low vitamin B12 levels. Current evidence suggests that low vitamin B12 levels are more common as the HIV disease progresses. The results of vitamin B12 treatment have been disappointing thus far, including the prevention of toxicity induced by azidothymidine. The possible role of vitamin B12 treatment in the long-term survival of HIV-infected patients is at present unknown. However, it is important to identify those patients who have real vitamin B12 deficiency to treat or prevent their hematologic and/or neurological symptoms.
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PMID:Cobalamin deficiency in patients infected with the human immunodeficiency virus. 993 May 70

In response to research findings that 10% to 30% of people aged 51 years and older may have protein-bound vitamin B-12 malabsorption, the National Academy of Sciences' Institute of Medicine recommends that these people consume a majority of the new Recommended Dietary Allowance (RDA) of 2.4 micrograms/day in its synthetic form rather than in its food form. Protein-bound vitamin B-12 malabsorption in older adults has been attributed to reduced pepsin activity and gastric acid secretion, which interfere with cleavage of vitamin B-12 from dietary protein before absorption. Unlike patients with pernicious anemia, most people with protein-bound vitamin B-12 malabsorption produce intrinsic factor and have the ability to absorb synthetic vitamin B-12 normally. Early diagnosis is necessary to prevent the untoward effects of vitamin B-12 deficiency. A thorough assessment of vitamin B-12 status entails measurement of multiple biochemical assessment indexes, including serum vitamin B-12, methylmalonic acid, and homocysteine concentrations. Dietitians and other health care professionals should be aware of the prevalence of vitamin B-12 deficiency in older adults and be familiar with sources of synthetic vitamin B-12 to facilitate implementation of the new RDA.
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PMID:Practitioners' guide to meeting the vitamin B-12 recommended dietary allowance for people aged 51 years and older. 1036 36

Because of the large liver stores (about 5 mg), low turnover rate (0.143%) and small daily requirement (3 micrograms), vitamin B12 deficiency does not occur under normal circumstances. This is not the case in individuals with chronic inflammatory or trophic changes at vitamin B12 absorption sites. Without supplementation, vitamin B12 deficiency can be expected within 5 years of gastrectomy. Characteristic features of type A gastritis are hyposecretion and mucosal atrophy in the fundus and body of the stomach, with absent intrinsic factor. In the small intestine, active and/or passive absorption is impaired by extensive ileal resection, exocrine pancreatic insufficiency and chronic inflammatory disorders such as Crohn's disease. Definitive plasma concentrations cannot be quoted for vitamin B12 deficiency. Dietary habits, subjective symptoms, hematological laboratory results, function tests and gastrointestinal endoscopic and histological findings must all be taken into account in the diagnosis. Modern diagnostic parameters, such as methylmalonic acid and homocysteine serum assays, are useful for achieving early diagnosis and hence optimal treatment. With their assured availability, parenteral vitamin B12 preparations remain the treatment of choice. Results from vitamin B12 bioavailability studies in healthy subjects suggest that > 300 micrograms probably suffices as an oral maintenance dose after parenteral loading. Further well-documented cases are needed in order to establish whether these doses are adequate in malabsorption syndromes and gastrointestinal diseases. Various case reports indicate the value of prophylactic and therapeutic oral vitamin B12 administration, especially in disorders of homocysteine metabolism, a substance postulated as a further important risk factor for atherosclerosis.
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PMID:Studies on vitamin B12 status in the elderly--prophylactic and therapeutic consequences. 1038 32

Cobalamin deficiency increases with advancing age. The cut-off point of serum concentration should be raised, because many elderly people with "normal" serum vitamin B12 concentrations are metabolically deficient in cobalamin. The measurement of the metabolites homocysteine and/or methylmalonic acid is recommended. Cobalamin deficiency may result in a variety of atypical symptoms. Hematological changes typical of megaloblastic anemia are absent in a majority of patients with neuropsychiatric disorders. Generally underlying pernicious anemia is not the main cause of cobalamin deficiency in the elderly. Protein-bound cobalamin malabsorption due to atrophic gastritis with hypo- or achlorhydria is a common cause of cobalamin deficiency in elderly people. An important manifestation of cobalamin deficiency is cognitive impairment. Much controversy exists on the subject of the association of dementia of the Alzheimer type with cobalamin deficiency. In several studies dementia has been related to low serum cobalamin levels. Physicians should be liberal of cobalamin therapy. The window of opportunity for effective intervention may be as short as one year from the onset of medical symptoms. At last a compilation of recommendations is given.
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PMID:[Vitamin B12 deficiency in geriatrics]. 1058 85

The application of sensitive metabolic tests, such as the deoxyuridine suppression test and measurement of homocysteine and methylmalonic acid, to cobalamin status has identified the entity of mild, preclinical cobalamin deficiency. This state, common in the elderly, responds to cobalamin therapy. Preclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect cobalamin deficiency. Interpretation of metabolic results still requires caution, as do proposals to raise the cut-off point for low cobalamin levels to capture some normal levels that are associated with metabolic abnormality. The recognition of mild, preclinical deficiency has opened up many important issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Although malabsorptive disorders, especially food-cobalamin malabsorption, underlie about half of all cases of preclinical deficiency, no cause can be found in the remainder of these cases; poor dietary intake appears to be uncommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly deficient mothers. All of these have broadened and complicated the picture of cobalamin deficiency while providing greater opportunities for prevention.
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PMID:Current concepts in cobalamin deficiency. 1077 70

Pernicious anaemia is an autoimmune atrophic gastritis inducing vitamin B12 deficiency by malabsorption. This disease may be diagnosed in the absence of any anaemia, on a neuropathy or when one or several autoimmune disorders co-exist. Typically, pernicious anaemia is revealed by macrocytic megaloblastic anaemia. Diagnosis is done on low serum vitamin B12, raised serum homocysteine, parietal cell and, intrinsic factor antibodies. Pernicious anaemia should be treated indefinitely by monthly intramuscular hydroxocobalamin. Because of an increased incidence of gastric carcinoma, endoscopy should be evenly performed.
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PMID:[Biermer's disease]. 1175 69

The vascular endothelium maintains a relatively vasodilated state via the release of nitric oxide (NO), a process that could be disrupted by hyperhomocysteinaemia. Since endothelial dysfunction is associated with increased systemic vascular resistance that is the hallmark of sustained arterial hypertension, we hypothesised that in patients with both hypertension and coeliac disease with hyperhomocysteinaemia (via malabsorption of essential cofactors), treatment of the latter disease could improve blood pressure (BP) control. A single patient with proven sustained hypertension and newly-diagnosed coeliac disease had baseline and post-treatment BP and endothelial function assessed by ambulatory BP monitoring (ABPM) and brachial artery forearm occlusion plethysmography respectively. This 49 year-old woman had uncomplicated sustained hypertension proven on repeated ABPM carried out 6 weeks apart (daytime mean 151/92 mm Hg and 155/95 mm Hg), and sub-clinical coeliac disease (gluten-sensitive enteropathy). Initial assessments revealed raised homocysteine levels with low normal vitamin B(12) level. It was likely that she had impaired absorption of essential cofactors for normal homocysteine metabolism. She adhered to a gluten-free diet and was give oral iron, folate and B(6) supplementations as well as B(12) injections for 3 months. Her BP had improved by 6 months and normalised by 15 months (daytime ABPM mean 128/80 mm Hg). There was parallel restoration of normal endothelial function with normalisation of her homocysteine levels. These observations suggest that sub-clinical coeliac disease related hyperhomocysteinaemia might cause endothelial dysfunction, potentially giving rise to a reversible form of hypertension. In addition, this case study supports the notion that irrespective of aetiology, endothelial dysfunction may be the precursor of hypertension. This highlights the need to resolve co-existing vascular risk factors in patients with hypertension.
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PMID:Reversible hypertension following coeliac disease treatment: the role of moderate hyperhomocysteinaemia and vascular endothelial dysfunction. 1203 96


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