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PubMed1993

[Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism].

Macrocytic megaloblastic anemia is the most typical but the latest sign of a cobalamin (vitamin B12) and/or folic acid deficiency or of a congenital abnormality of cobalamin and folate metabolism. Macrocytosis in blood and megaloblastosis in bone marrow are the morphological features of a disturbance in cell division related to a defect in DNA biosynthesis. Macrocytosis without anemia, normocytic normochronic anemia with a low reticulocyte cell count or microcytic hypochromic anemia in case of associated iron deficiency do not exclude a vitamin deficiency. Neurological or psychiatric disorders and immune abnormalities have been reported in patients with vitamin B12 or folate deficiencies or in children with congenital abnormalities of these 2 vitamins; such manifestations may even occur without anemia.

Anemia, Megaloblastic↗
PubMed2001

[Diagnostics for classification of anemia].

Examining peripheral blood smears provides valuable information in the diagnosis of anaemia despite large inter- and intraobserver variation. The classification of anaemia is usually based on the average erythrocyte size, referred to as the mean corpuscular volume (MCV). Microcytosis indicates a reduced haemoglobin synthesis caused by either an iron deficiency or haemoglobinopathy, a congenital disorder. Macrocytosis is the result of a disruption to the division and maturing of proerythroblasts in the bone marrow, due, for example, to vitamin B12 (folic acid) deficiency or excessive alcohol use. Furthermore, a high number of reticulocytes in the blood indicates an increased production of erythrocytes whereas a low total indicates an inadequate production level. In addition to the case history and the physical examination, the MCV and number of reticulocytes can provide guidance with respect to further diagnostic investigation.

Algorithms↗
PubMed1978

Methionine toxicity in chicks and poults.

In feeding experiments with poults, 2% DL-methionine caused a marked growth depression which could be alleviated by the addition of glycine. Homocystine at an equimolar level depressed growth to a lesser degree than methionine, and this growth depression could be alleviated by glycine. Betaine could alleviate the growth depression of homocystine but not that of methionine. Methionine-fed poults developed a cervical paralysis similar to that of a folic acid deficiency, but the addition of this vitamin at several times the requirement was ineffective in counteracting the toxicity of methionine in either chicks or poults.

Animals↗
PubMed1999

[Diagnostic significance of mild hyperhomocysteinemia in a population of children with parents or grandparents who have peripheral or coronary artery disease].

BACKGROUND: A rise of the homocysteine plasma level--mild hyperhomocysteinaemia--is considered an independent risk factor for the development of vascular damage. It is due to hereditary deficiency of 5,10-methylene-tetrahydrofolate reductase with accentuation of vitamin deficiency (folic acid, vitamin B6 and B12). In previous studies the authors confirmed this fact in the population of patients with aortocoronary or peripheral arterial bypasses. The assumed autosomal recessive transmission of this deficiency should make it possible to detect carriers of this metabolic deviation already in childhood. By selective screening of the child population at risk it would thus be possible to detect affected subjects in time and prevent the development of vascular disease by preventive folate administration. METHODS AND RESULTS: In a group of 38 children and grandchildren from risk families where at least one of the parents or grandparents was operated on account of vascular obliterating disease the total homocysteine plasma level was examined by the chromatographic method. An increase of total homocystein (8.7 +/- 2.7 mumol/l) was found as compared with children from the non-risk population (5.4 +/- 1.8 mumol/l), (p < 0.001). The total homocysteine values however were dependent on the child's age and were more marked in children above 12 years of age. In the parental population mild hyperhomocysteinaemia was present in 38% of those with aortocoronary bypasses and in 43% of those with peripheral arterial bypasses. CONCLUSIONS: The authors found significantly elevated total homocysteine levels in the child population from risk families with obliterating vascular disease. The total homocysteine level depends on the child's age and is more markedly expressed in children above 12 years of age.

Adolescent↗
PubMed1995

Gestation and lactation of dairy cows: a role for folic acid?

Twenty-four multiparous and 16 primiparous dairy cows were assigned by parity, BW, and milk production to 20 blocks of 2 cows each. Within each block, the cows were injected weekly with either 0 or 160 mg of folic acid from 45 d after mating to 6 wk after parturition. Supplementary folic acid augmented the placental and colostral transfer of folates to the calf but had no effect on blood hemoglobin, birth weight, or growth and feed intake of the calf during the first 10 wk of life. The supplemental folic acid increased serum folates but had no marked effect on blood hemoglobin and BW of cows. Supplementary folic acid tended to increase milk folates, milk production, and the percentage of milk protein during the last half of the lactation curve but had no effect on milk folates and milk production during the first 6 wk after parturition when the injections of folic acid increased the percentage of milk protein in multiparous cows but had no effect on primiparous cows. The supply of folates by the diet and the synthesis by ruminal microflora is sufficient to prevent folic acid deficiency in dairy cows and to maintain normal gestation and lactation, but not to achieve maximal production of milk and protein in multiparous dairy cows during gestation and lactation.

Animals↗
PubMed1998

A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages.

OBJECTIVE: To evaluate the medical relevance of hyperhomocysteinemia in women with primary recurrent miscarriages. DESIGN: Case report and retrospective cross-sectional study. SETTING: Hematology outpatient department of a university hospital. PATIENT(S): Case report concerning a woman with five consecutive fetal losses. One hundred consecutive women with primary recurrent unexplained miscarriages (study group) and matched healthy controls (control group) with no antecedent fetal loss. INTERVENTION(S): Venous blood sample collection in resting individuals. MAIN OUTCOME MEASURE(S): Plasma total homocysteine concentrations, plasma folate concentrations, and DNA analysis for the C677T mutation of the 5,10 methylene tetrahydrofolate reductase gene. Normal threshold homocysteine concentration was obtained from values found in the control group (95th percentile). RESULT(S): The case patient was hyperhomocysteinemic, was homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene, and had plasma folate deficiency. Folic acid and pyridoxine administration normalized the homocysteine concentration and favored a successful pregnancy. In the retrospective study, 12 of 100 patients were hyperhomocysteinemic. Twenty percent had the C677T methylene tetrahydrofolate reductase genotype and 15% had low plasma folate concentrations. The highest values of homocysteine concentration were found in patients with both the C677T genotype and folate deficiency. CONCLUSION(S): Hyperhomocysteinemia should be identified in women with recurrent miscarriages because therapeutic normalization might permit a normal birth.

Abortion, Habitual↗
PubMed1966

An account of 335 cases of megaloblastic anaemia of pregnancy and the puerperium.

The incidence of megaloblastic anaemia in pregnancy and the puerperium in north Staffordshire has steadily declined as a result of prophylaxis with folic acid. In the presence of advanced folic acid deficiency and with a florid megaloblastic marrow, the anaemia is usually severe, but in many patients the disease is relatively mild and the degree of anaemia is determined more by blood loss or associated iron deficiency than by the megaloblastosis. Microscopic examination of marrow films is still the most reliable method of diagnosis, although estimation of the labile serum folate has produced a 95% correlation with the marrow findings. There are three main factors which operate in the pathogenesis of megaloblastic anaemia in pregnancy and the puerperium. First, the maternal stores of folic acid are used up by the growing foetus, and this process is accelerated in multiple pregnancies, after haemorrhage, or in women with haemolytic anaemia. Secondly, an insufficient intake of folic acid, due to poor diet in pregnancy, plays a part in many cases. The third, and possibly the most important, factor is an absorption defect. Folic acid absorption is usually impaired in established cases, and this can still be demonstrated years later in a majority of patients, when they are neither pregnant nor anaemic. More than 20% of all cases also show abnormal fat absorption. An inherited defect in folic acid absorption may also explain why certain women appear to be constitutionally predisposed to megaloblastic anaemia of pregnancy and the puerperium, as shown by the abnormal blood group distribution in these patients and by the tendency of megaloblastic anaemia to recur not only in subsequent pregnancies, but, as in six of our cases, following other kinds of stress. The significance of commonly associated conditions like pre-eclampsia and infection is still incompletely understood. Although the treatment of megaloblastic anaemia is simple and effective, the main emphasis should be placed on prophylaxis by administering folic acid to all pregnant women.

Adult↗
PubMed1977

An automated method of differential red blood cell classification with application to the diagnosis of anemia.

A method of automated red cell analysis suitable for the rapid classification of large numbers of red cells from individual blood specimens has been developed, and preliminarily tested on normal bloods and clinically proven cases of anemias and red cell disorders. According to this method digital image processing techniques provide several features relating to shape and internal central pallor configurations of red cells. These features are used with a fully automated decision logic to rapidly provide a quantitative "red cell differential" analysis, a report of the percentage subpopulations of recognized categories of red cells. For each subpopulation, measurements of mean cell area, mean cell hemoglobin content and mean cell hemoglobin density are provided. The nine types of red cell disorders studied with this method were: (a) iron deficiency anemia, (b) the anemia of chronic disease, (c) beta-thalassemia trait, (d) sickle cell anemia, (e) hemoglobin C disease, (f) intravascular hemolysis, (g) hereditary elliptocytosis, (h) hereditary spherocytosis, and (i) megaloblastic anemia due to folic acid deficiency. Preliminary indications are that the red cell differential is useful in distinguishing between these conditions.

Anemia↗
PubMed2005

High prevalence of folic acid and vitamin B12 deficiencies in infants, children, adolescents and pregnant women in Venezuela.

BACKGROUND: There is increased worldwide concern about the consequences of folic acid and vitamin B12 deficiencies on health, which include megaloblastic anemia, neural tube defects and cardiovascular disease. OBJECTIVE: This study intended to determine the prevalence of folic acid and vitamin B12 deficiencies in vulnerable groups in labor and poor socioeconomic strata of the Venezuelan population. METHODS: A total of 5658 serum samples were processed to determine folic acid and vitamin B12 concentrations. The study involved three surveys performed during 2001-2002 and included infants, children, adolescents and pregnant women from labor and poor socioeconomic strata of the population. The method used was a radio immunoassay designed for the simultaneous measurement of serum folic acid and vitamin B12. RESULTS: The prevalence of folic acid deficiency was higher than 30% for all groups studied, reaching 81.79% in adolescents. Vitamin B12 deficiency was 11.4% in samples collected nationwide, but there was also a similar prevalence of high serum levels. The prevalence of folic acid and vitamin B12 deficiencies in pregnant women reached 36.32 and 61.34%, respectively. CONCLUSION: This work shows that there is a high prevalence of folic acid deficiency, especially in women of reproductive age, pregnant adolescents and in the whole population studied in Vargas state. This situation requires immediate intervention as supplementation or food fortification programs.

Adolescent↗
PubMedDate not supplied

Drug and environmental factors associated with adverse pregnancy outcomes. Part I: Antiepileptic drugs, contraceptives, smoking, and folate.

OBJECTIVE: Part I of this review examines the relationship between antiepileptic drugs (AEDs) and pregnancy outcomes. Drug-induced folate deficiency and the role of AED metabolism are emphasized. Part II will discuss periconceptional folate supplementation for prevention of birth defects. Part III will discuss the mechanism of folate's protective effect, therapeutic recommendations, compliance, and cost. DATA SOURCES: A MEDLINE search was conducted for journal articles published through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included phenytoin, carbamazepine, phenobarbital, primidone, valproic acid, oral contraceptives, clomiphene, drug-induced abnormalities, spina bifida, anencephaly, neural tube defect, folate, folic acid, and folic acid deficiency. STUDY SELECTION: Relevant animal and human studies examining the effects of AEDs, smoking, and oral contraceptives on folate status and pregnancy outcome are reviewed. DATA EXTRACTION: Studies and case reports were interpreted. Data extracted included dosing, serum and red blood cell folate concentrations, teratogenicity of anticonvulsant medications, metabolism of AEDs and folate, and genetic susceptibility to AED-induced teratogenicity. DATA SYNTHESIS: Low serum and red blood cell folate concentrations are associated with adverse pregnancy outcomes. Decreases in serum folate are seen with AEDs, oral contraceptives, and smoking. Since similar birth defects are observed with multiple AEDs, metabolism of aromatic AEDs to epoxide metabolites and genetic factors may play a role in teratogenesis. CONCLUSIONS: Adequate prepregnancy planning is essential for women who have epilepsy. Women receiving folate-lowering drugs may be at increased risk of adverse pregnancy outcomes. Therefore, epileptic women contemplating pregnancy should be treated with the minimum number of folate-lowering drugs possible and receive folic acid supplementation.

Anticonvulsants↗
PubMed1988

Spontaneous expression of fra(10)(q25) in bone marrow from a patient with agranulocytosis.

We report on the spontaneous expression of fra(10)(q25) in bone marrow from a patient with agranulocytosis. Expression of this fragile site in both bone marrow and leukocytes was enhanced by bromodeoxyuridine (BrdU), while folic-acid-deficient medium enhanced the expression of fra(10)(q25) only in leukocytes. Variability in the expression of fra(10)(q25) in bone marrow and leukocyte cultures over an 18-month period was also found.

Adult↗
PubMed2005

Plasma levels of amino acids in elderly long term care residents with oropharyngeal dysphagia: comparison of hand-oral with tube-enteral-fed patients.

BACKGROUND: Dysphagia and eating difficulties are highly prevalent in long term care patients. Evaluation of their nutritional status is complicated by comorbidity, frailty and individual patterns of feeding. In previous studies we found vitamin deficiencies (folic acid B6 and B12) in orally fed elderly in early stages of oropharyngeal dysphagia despite satisfactory nutritional parameters (BMI, albumin and hemoglobin). The aim of this study is to evaluate the plasma amino acids levels in these hand-oral fed elderly patients with dysphagia. METHODS: Plasma amino acids were measured in 15 orally fed elderly patients in early functional outcome swallowing scale (FOSS), stage 2, and compared with those of 15 matched nasogastric-tube-fed counterparts. RESULTS: The plasma levels of all measured amino acids, ratio of essential to nonessential, levels of conditionally essential and the immune-enhancing amino acids were similar in both groups and within the normal range of our laboratory. The traditional nutritional parameters were also similar in both groups and within the normal range. CONCLUSIONS: Plasma levels of amino acids in elderly patients in early stage of FOSS are satisfactory, supporting the view that their protein intake is adequate. Further studies should concentrate on patients in advanced stages of FOSS.

Administration, Oral↗
PubMed1998

Age-related changes in cobalamin (vitamin B12) handling. Implications for therapy.

Cobalamin (vitamin B12) deficiency is more common in the elderly than in younger patients. This is because of the increased prevalence of cobalamin malabsorption in this age group, which is mainly caused by (autoimmune) atrophic body gastritis. Cobalamin supplementation is affordable and nontoxic, and it may prevent irreversible neurological damage if started early. Elderly individuals with cobalamin deficiency may present with neuropsychiatric or metabolic deficiencies, without frank macrocytic anaemia. An investigation of symptoms and/or signs includes the diagnosis of deficiency as well as any underlying cause. Deficiency states can still exist even when serum cobalamin levels are higher than the traditional lower reference limit. Cobalamin-responsive elevations of serum methylmalonic acid (MMA) and homocysteine are helpful laboratory tools for the diagnosis. The health-related reference ranges for homocysteine and MMA appear to vary with age and gender. Atrophic body gastritis is indirectly diagnosed by measuring serum levels of gastrin and pepsinogens, and it may cause dietary cobalamin malabsorption despite a normal traditional Schilling's test. The use of gastroscopy may also be considered to diagnose dysplasia, bacterial overgrowth and intestinal villous atrophy in healthy patients with atrophic body gastritis or concomitant iron or folic acid deficiency. Elderly patients respond to cobalamin treatment as fully as younger patients, with complete haematological recovery and complete or good partial resolution of neurological deficits. Chronic dementia responds poorly but should, nevertheless, be treated if there is a metabolic deficiency (as indicated by elevated homocysteine and/or MMA levels). Patients who are at risk from cobalamin deficiency include those with a gastrointestinal predisposition (e.g. atrophic body gastritis or previous partial gastrectomy), autoimmune disorders [type 1 (insulin-dependent) diabetes mellitus and thyroid disorders], those receiving long term therapy with gastric acid inhibitors or biguanides, and those undergoing nitrous oxide anaesthesia. To date, inadequate cobalamin intake has not proven to be a major risk factor. Intervention trials of cobalamin, folic acid and pyridoxine (vitamin B6) in unselected elderly populations are currently under way.

Aged↗
PubMed1983

Effect of a synthetic folic acid analogue, 9-methyl-pteroylglutamic acid, on fetal chondrogenesis: ultrastructural observations.

Maternally administered folic acid antagonists (x-methyl-PGA and 9-methyl-PGA) are known to produce various skeletal malformations in the neonate. These defects are thought to be due in part to abnormal metabolism and/or deposition of various extracellular matrix components, i.e., collagen and glycosaminoglycans. Experimental reduction of glycosaminoglycan biosynthesis in vitro has been shown previously to alter the spatial orientation and normal pattern of collagen fibrillogenesis. Furthermore, dietary withdrawal of folic acid concomitant with maternal administration of 9-methyl-PGA has been shown to result in abnormal collagen, uronic acid, and hexosamine metabolism by fetal limbs. In the present study pregnant rats were exposed to a transitory folic acid deficiency from day 11 to 14 of gestation and fetal tibias (mid-diaphyseal region) were examined with the electron microscope on day 18 of gestation. Although we were unable to ascertain any aberrant patterns of fibrillogenesis and orientation with respect to collagen, this particular teratogenic regimen resulted in an altered pattern of chondrocyte development when observed at the ultrastructural level.

Abnormalities, Drug-Induced↗
PubMed1976

Anemia--a common but never a normal concomitant of aging.

Diagnosis is often overlooked because symptoms develop slowly and insidiously and many patients don't complain about them. Then too, the giddiness, apathy, confusion, clumsiness, and similar problems may be considered simply signs of "old age." Iron deficiency anemia is the most common type in old people. It's usually due to gastrointestinal bleeding, but there may be a second, less obvious cause. The classic picture of low serum iron, high total iron-binding capacity, and low iron-binding saturation is sometimes distorted. Usually, many studies are needed to confirm the suspicion of a vitamin B12 or folic acid deficiency. A raised mean corpuscular volume in itself signals the need for further investigation. In patients with macrocytosis, the bone marrow must be examined. Tests for intestinal malabsorption must be considered too. Repeated blood tests are essential in patients being treated for any type of anemia. Iron deficiency may hide evidence of folate or B12 deficiency. And iron therapy may lessen bleeding from colonic cancer, delaying diagnosis until it's too late to operate.

Aged↗
PubMed1998

[Vitamin B 12 deficiency: early diagnosis in ambulatory care medicine].

Many patients suffer from vitamin B12 deficiency and are thus exposed to irreversible sequelae if diagnosis occurs at a late stage. This prospective study undertaken by eight practitioners over a period of 12 months concerns early diagnosis. Blood vitamin B12 levels were measured in 152 patients presenting macrocytosis detected by systematic MCV analysis at the time of a blood test, a neuropathy or a recent cognitive, affective and behavioural problem, and were found to be lowered (< or = 175 pmol/l) in 54 patients of whom 43 had undergone vitamin B12 test treatment for 6 months. Haematological, neurological and psychiatric evaluation was carried out before and after treatment, and a diagnosis of deficiency was recorded in 24 patients based on unequivocal response to therapy. Improvement was greatest haematologically in 12 patients, neurologically in 6 patients and psychiatrically in 6 other patients, with 4 patients showing a combination of all modes. These 24 patients (mean age 69 years) suffered from numerous pathologies which were liable to complicate diagnosis in some of them: neurological (46%), psychiatric (37%), chronic alcoholism (33%), folic acid deficiency (29%), and diabetes (17%). The only diagnostic element used as a criterion of deficiency was an extremely low level of vitamin B12 (< or = 75 pmol/l). Marked macrocytosis or a combination of haematological and neuropsychiatric signs are strong indicators, but only improvement under treatment allowed a diagnosis to be made in the majority of patients. Macrocytosis was, however, not present in 6 of the 12 neuropsychiatric patients. The study thus identified a high proportion of patients with vitamin B12 deficiency who additionally presented, in equal proportions, both haematological and neuropsychiatric symptoms. Neither the clinical examination nor the vitamin B12 level in general permit early diagnosis based on a high probability index and long-term follow-up. Simpler methods for early diagnosis are therefore needed.

Aged↗