Benign proximal tubular albuminuria due to AMN mutation: A challenging presentation of Imerslund-Gräsbeck syndrome.

Vitamin B₁₂Deficiency and Depression in the Elderly

Venous thromboembolism (VTE) is a multi-factorial disease involving numerous genetic and environmental risk factors. In this study we investigated the occurrence and the risk associated with factor V Leiden, hyperhomocysteinemia and low folate and vitamin B12 levels in young patients with thrombosis. We studied 78 patients (33 females/45 males, mean age 33 years) with a history of thrombosis in a lower limb. Additionally, 98 healthy subjects (45 females/54 males, mean age 44 years) were included. Serum levels of homocysteine (Hcy), folate and vitamin B12 were assayed. Factor V Leiden and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated in all subjects. Factor V Leiden was highly prevalent in the patients (39% heterozygous, 10% homozygous vs. 6.3% heterozygous in controls). An increase in the risk of idiopathic VTE was associated with Hcy levels > 15.2 micromol/l (odds ratio, OR = 2.83), folate < 15.1 nmol/l (OR = 7.49) and vitamin B12 < 182 pmol/l (OR = 11.97). Low levels of folate or vitamin B12 were independently and strongly associated with the risk of VTE in a multivariate model (OR for idiopathic thrombosis = 16.44 and 10.76, respectively). Twenty patients (53%), carriers of factor V Leiden, had low levels of vitamin B12, compared to 28% of patients who were non-carriers of the mutation (p = 0.03). In contrast, none of the control carriers of the mutation had a low level of vitamin B12. The risk of VTE associated with lower levels of vitamin B12 and folate was stronger than that introduced by elevated Hcy levels. The increased risk of VTE, accompanied by factor V Leiden, may be related to confounding environmental factors.

Undernutrition as well as low levels of vitamin B12 and folic acid are common problems among older adults. However, recommended routine nutritional status assessment tools may result in inadequate vitamin serum levels to go unnoticed. Therefore, the aim of this study is to evaluate the inadequacy of serum levels of vitamin B12 and folic acid within Mini Nutritional Assessment (MNA) classification categories among older adults. A cross-sectional study was conducted with 97 older adults residing in care homes in Portugal. Undernutrition was identified through the MNA, and serum levels of vitamin B12 and folic acid were measured using chemiluminescence. Cognitive function, depressive symptoms and functional characteristics were also assessed using the Abbreviated Mental Test Score, the Epidemiologic Studies Depression Scale and the Barthel Index, respectively. The mean age of older adults was 82.2 (6.3) years; 3.1% were undernourished and 26.8% were at undernutrition risk. In the MNA normal nutritional status group, 11.8% presented vitamin B12 deficiency (<200 pg/ml), 32.4% had low serum levels (200-400 pg/ml) and 4.4% had folic acid deficiency (<3 ng/ml). A high proportion of older adults with low serum levels of vitamin B12 presenting normal nutritional status by MNA was identified. This finding emphasizes the need to evaluate serum vitamin B12 levels, independently of the MNA results.

Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported. Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients. Given the lack of studies in frontotemporal dementia (FTD) and on folate and given the methodological shortcomings of former publications, we set up a prospective study. At inclusion, AD (n=152) and FTD (n=28) patients underwent a neuropsychological examination. Behaviour was assessed using a battery of behavioural assessment scales. Determination of serum vitamin B12 and red cell folate levels were performed within a time frame of two weeks of inclusion. In both patient groups, significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found. No correlations with BPSD were found in the AD patient group. In FTD patients, levels of vitamin B12 were negatively correlated with both hallucinations (p=0.022) and diurnal rhythm disturbances (p=0.036). The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients, raise the possibility of a non-specific etiological role. Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients, negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed. Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances.

PurposeTo evaluate the prevalence of abnormal vitamin B12, folate, total homocysteine (tHcy), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) levels, to analyze the relationship between these parameters and the severity of anxiety or depressive symptoms, and to explore the possible factors associated with abnormal levels of these parameters in adolescents with anxiety or depressive symptoms.MethodsAdolescent (aged 12–18 years) outpatients with anxiety or depressive symptoms were recruited. The patient health questionnaire-9 and generalized anxiety disorder scale-7 were used to measure the severity of depression and anxiety. Serum vitamin B12, folate, tHcy, IL-6, TNF-α, and CRP levels were determined.Results128 subjects were recruited. The prevalence of vitamin B12 and folate deficiency, tHcy, TNF-α, IL-6, and CRP elevation was 8.6%, 10.2%, 25.8%, 14.8%, 21.9%, and 10.2%, respectively, in adolescents with anxiety or depressive symptoms. Lower vitamin B12 levels were correlated with a higher risk of severe anxiety and depressive symptoms. The severity of some symptoms of anxiety or depression were weakly correlated with vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were not associated with inflammatory mediators. Vitamin B12 deficiency was associated with older age and higher tHcy levels. Folate deficiency was associated with elevated tHcy. Elevated tHcy was associated with lower vitamin B12 and folate levels. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking.ConclusionLower vitamin B12 levels were correlated with a higher risk of severe anxiety or depressive symptoms. Weak correlations were observed between the severity of some symptoms of anxiety or depression and vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were related to each other. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking.

To determine whether immunocompetent elderly patients with low serum vitamin B12 levels have impaired serum antibody responses to the 23-polyvalent pneumococcal polysaccharide vaccine. Controlled, prospective cohort study. 15 patients with low serum vitamin B12 levels and 15 age- and diagnosis-matched patients with normal levels were vaccinated. Serum antibody titers to 12 pneumococcal serotypes were measured by radioimmunoassay before and 4 weeks after vaccination. The difference between the geometric mean of the vaccine antibody titers before and after vaccination for all 12 serotypes was lower (P = 0.005) in the patients with low vitamin B12 levels than in the patients with normal levels. When mean corpuscular volume and age were controlled for, vitamin B12 remained an independent predictor of antibody response (P = 0.005). Erythrocyte mean corpuscular volume was also an independent predictor of the increase in titer (P = 0.03). Patients with low vitamin B12 levels had impaired antibody responses to pneumococcal vaccine. Further study is necessary to determine whether treatment with vitamin B12 can enhance specific immunoglobulin synthesis and improve the clinical efficacy of the pneumococcal vaccine in patients with low vitamin B12 levels.

In cross-sectional studies periventricular white matter lesions (WML) were related to low plasma levels of vitamin B12. Whether low vitamin B12 levels are also related to progression of WML is still unknown. We studied baseline vitamin B12 levels and its association with progression of WML over 2 years of follow-up in first-ever lacunar stroke patients. In 107 first-ever lacunar stroke patients in whom baseline brain MRI and vitamin B12 status were available, we obtained a follow-up brain MRI after 2 years. We assessed progression of periventricular WML (pWML) and deep WML (dWML) using a visual WML change scale. We studied the relationship between baseline levels of plasma vitamin B12 and progression of WML after 2 years of follow-up by binary logistic regression analyses. Vitamin B12 deficiency was more frequent in patients with progression of pWML compared to those without progression (41.9% and 19.7% respectively, p = 0.02). Corrected for sex and age, progression of pWML was associated with lower baseline levels of vitamin B12 (OR 1.42 per 50 unit decrease, 95% CI 1.00-1.92). Vitamin B12 levels were not associated with progression of dWML. In conclusion progression of pWML after 2 years of follow-up relates to low levels of vitamin B12 at baseline in first-ever lacunar stroke patients. Whether this population could benefit from vitamin B12 supplementation is unknown and requires further investigation.

We studied the effect of low levels of vitamin B12 and folic acid, alone or combined, on cognitive performance in a population-based sample of 698 older adults (mean age = 68.7 years). No evidence was found for a vitamin-related memory deficit, but research participants with low levels of vitamin B12 exhibited reduced information processing speed relative to participants with normal vitamin B12 levels.

Objective: The purpose of the study is to observe the metformin associated effects on Vitamin B12 among Type II Diabetes mellitus patients. Methods: An observational study conducted over the period of 12 months on Type II Diabetes mellitus patients who are in the chronic therapy of metformin. The study described about the Vitamin B12 levels among the Type II DM patients which was able to alert the patients who are in the low and border range of Vitamin B12 to prevent the risk of peripheral neuropathic complications. Findings: Totally 102 patients were enrolled as per the inclusion and exclusion criteria, during the study total 61 males (59.8%) and 41 females (40.2%) were enrolled. Among them 12 patients (mean 49.16±S.D10.53) on low level of the Vitamin B12 followed by 16 patients (mean 51.95±S.D7.12) found to above the normal range of the Vitamin B12 followed by 30 (mean 57.53±S.D4.55) patients found to borderline of the Vitamin B12. Conclusion: High doses with chronic therapy of Metformin may alter Vitamin B12 level. Some of the patients had been observed abnormal level of higher value of Vitamin B12. In such Patients’ diet history also had some impact on Vitamin B12. However, the high chances of metformin associated effect on Vitamin B12 with higher doses of metformin with long term therapy. Moreover, age also important fact that the study reveals among gender, male population had higher rate of low level Vitamin B12 than female population. Moreover, Patients age group between 50 and 65(male58 ± 3.58, female 57.16±3.81) were having higher rate of low level Vitamin B12 than other age group. Patients with other comorbid condition also had low level and borderline of Vitamin B12 those who were on long term therapy of metformin. Therefore, our study concluding that chronic therapy of metformin may lead to deficit in serum Vitamin B12 which required regular check on Vitamin B12 among Type 2 DM patients to avoid the risk of Peripheral neuropathy and other complications.

Background: Vitamin B12 plays an important role in many metabolic pathways, obesity, and insulin resistance and the elderly as a high-risk group are prone to its deficiency. In this regard, this study investigated the relationship between serum vitamin B12 and glycemic indices, dietary components and body mass index (BMI) in elderly population.Methods: In a cross-sectional study, ninety elderly aged 65 years and older from an senior center were enrolled. After completing the demographic questionnaire and assessing BMI, 5 mL blood sample was provided to measure serum vitamin B12, insulin and blood glucose levels. On the other hand, the vitamin B12 content of the diet was extracted from thefood frequency questionnaire (FFQ).Results: About 58% of the elderly had serum vitamin B12 levels below normal. There was a significant correlation between low vitamin B12 levels, body weight and BMI. Furthermore, the relationship between low serum vitamin B12 level and fasting blood glucose level was also significant (p <0.05). FFQ results indicated a significant relationship between serum vitamin B12 level and the amount of different types ofmeat and eggs.Conclusion: The favorable level of vitamin B12 was shown to play a role in hyperglycemia control and to reach a normal weight.

Case control studies have supported a relationship between low folic acid and vitamin B112 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations. A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging. Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables. Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.

Metformin is associated with low levels of vitamin B12 with no effect on other vitamin levels. A selective action of metformin.

Aims To compare vitamin B12, homocysteine, and anti-parietal cell antibody (APCA) levels between children with ASD and controls, paired in terms of age, sex, and socioeconomic level. Methods The research group consisted of 69 children, 36 with ASD and 33 controls. The severity of ASD was determined using the Childhood Autism Rating Scale (CARS). Serum vitamin B12, homocysteine and human anti-parietal cell levels were analysed using enzyme-linked immunosorbent assay. Results The serum vitamin B12 and homocysteine levels in children with ASD were lower than in the control group, but there was no significant difference in terms of APCA levels. Conclusions Deficiencies in micronutrients, such as B12, may play a role in the pathogenesis and clinical symptoms of autism. However, it is believed that these parameters should be analysed in a wider population to clarify their effect on the aetiology of ASD. KEY POINT We hypothesised that low levels of vitamin B12 and homocysteine levels reported in previous studies might be associated with APCA levels. The homocysteine and B12 levels were found to be significantly lower in children with ASD. There was no significant difference in serum APCA levels. No significant relationship was found between B12 levels and APCA. Given all these findings, it can be stated that vitamin B12 deficiency is not associated with an absorption-related mechanism due to the presence of APCA. Deficiencies in micronutrients, such as B12, may play a role in the pathogenesis and clinical symptoms of autism. In future studies, it will be beneficial to investigate other mechanisms that may cause vitamin B12 deficiency.

Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03-2.95, p = 0.04). High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

INTRODUCTION: A potential role of Homocysteine (HCY) in bone metabolism has been considered from the observation of high prevalence of osteoporosis in subjects with Homocystinuria about 50 years ago. But the mechanism linking the increased level of HCY to increased fracture risk is not clear. The objective of this study was to investigate this possible relationship between vertebral fractures and HCY level in Moroccan postmenopausal women. METHODS: one hundred and twenty-two healthy postmenopausal women gave their informed consent to participate in this cross-sectional study. Women were recruited through advertisements and mouth to ear between January 2017 and May 2017. Bone mineral density was determined by a Lunar Prodigy Vision DXA system. Vertebral fracture assessment image was inspected visually by 2 clinicians. RESULTS: we found that a high level of HCYor low levels of vitamin B12 and folates are not associated to the bone mineral density and are not risk factors for vertebral fractures in healthy postmenopausal women. Whereas, the presence of vertebral fracture was associated to the number of years since menopause and to the OC level. Probably this is due to the young age of the patients involved in this study. We also showed that high level of HCY is associated with the number of years since menopause and not age for women. CONCLUSION: we found that a high level of HCY or low levels of vitamin vitamin B12 and folates are not associated to the bone mineral density and are not risk factors for vertebral fracture in healthy Moroccan postmenopausal women.