Cobalamin binding proteins in patients with HIV infection

Abstract: P-Cobalamins have been reported to be decreased in patients with HIV infection. Because of this, we found it of interest to examine both cobalamin-saturated binding proteins (holo-transcobalamin, holo-TC and holo-haptocorrin, holo-HC) and cobalamin unsaturated binding proteins (apo-transcobalamin, apo-TC and apo-haptocorrin, apo-HC). The results are given as range and (median). Eighteen male HIV-infected patients with plasma cobalamins below 200 pmol/1 were studied. We found low concentrations of holo-TC (37–88 (47.5) pmol/1) and holo-HC (64–184 (135.5) pmol/1). The concentration of apo-TC and apo-HC was increased (480–1730 (1025) pmol/1; 70–800 (235) pmol/1). It is concluded that, in HIV-infected patients, low plasma cobalamin does not reflect a low concentration of transcobalamin or haptocorrin. In 20 HIV-infected patients and 31 patients with malignant haematological diseases, the TC isopeptide patterns were determined. In the HIV group, an increased frequency of TC isopeptide X was found and the overall distribution of TC isopeptides was significantly different from the reference population (p < 0.05). There was no difference between the group of patients with malignant haematological diseases and the reference group.     

Increased Concentration of Transcobalamin I in a Patient with Metastatic Carcinoma of the Breast

A patient with metastatic carcinoma of the breast and increased plasma cobalamin binding capacity (about 50 nmol/1) is described. The binding protein was identified as transcobalamin I (TCI) by DEAE cellulose ion-exchange chromatography, Sephadex G200 gel filtration and agar gel electrophoresis. Although the total plasma cobalamin concentration (about 20 nmol/1) was elevated, the patient complained of neurological symptoms in accordance with a functional vitamin B₁₂ deficiency. Hence, an inactivation of the coenzyme is suggested by the demonstration of considerable amounts of 5′-deoxyadenosylcobalamin bound to the plasma TCI. Both urinary excretion of FIGLU and methylmalonic acid were within the reference ranges. Reported cases of increased cobalamin binding in patients with nonhaematological malignancy are reviewed. Further investigations to characterize the function of the cobalamin dependent metabolic pathways are necessary to determine the importance of the increased transcobalamin binding in these patients.     

Vitamin B12 Metabolism in Myelomatosis

In 38 patients with myelomatosis the serum cobalamin varied from 34 pmol/l to 404 pmol/l, median 181.5 pmol/l, which is significantly lower than the levels in 22 control persons with range 173–535 pmol/l, median 265 pmol/l. In spite of low serum cobalamin no symptoms of vitamin B₁₂ deficiency could be demonstrated in any of the patients, except for the one patient who had a serum cobalamin of 34 pmol/l. Mean values for Hb, MCV, PCV, serum lactate-dehydrogenase, adjusted red cell folate and nucleated neutrophil count were similar in a group of patients with a serum cobalamin below 160 pmol/l and a group of patients with higher serum cobalamin values. The decrease in serum cobalamin is due in part to a reduction in the major cobalamin binder (TC-I) in serum. Measuring serum cobalamin in relationship to gastric acid secretion, we found a significantly higher frequency of hypo- and achlorhydria in patients with serum cobalamin below 160 pmol/l although the intestinal absorption of vitamin B₁₂ was normal by a Schilling test. Although our finding of low saturation of TC-I in serum seems to demonstrate decreased vitamin B₁₂ content in the body in myelomatosis, the lack of evidence for a functional vitamin B₁₂ deficiency speaks against giving a supplement to patients with myelomatosis.     

Serum vitamin B12 and folate status among patients with chemotherapy treatment for advanced colorectal cancer

Background. There are conflicting results on the role of cobalamin and folate for epidemiology and carcinogenesis in colorectal cancer patients and the need of supplementation for prevention of chemotherapy toxicity.

Patients and methods. Serum cobalamin, folate, and homocysteine were analysed before and during the treatment of 93 patients with advanced colorectal cancer (ACRC) with first-line chemotherapy treatment. This cohort was compared with a healthy control group of 224 individuals.

Results. Patients with ACRC had similar cobalamin, folate, and homocysteine values as the healthy control group. There were no correlations between serum cobalamin, folate, and homocysteine values and objective response. There were no correlations to anaemia or other severe toxicity for cobalamin and homocysteine. A total of 12 patients had folate deficiency, and 10 of those suffered from severe toxicity (grade 3 or more). All patients had markedly increased folate values after 2 months of treatment. Folate and homocysteine did not predict patient outcome; however, patients with subclinically low cobalamin values (<300 pmol/L) had significant better overall survival and time to progression than patients with normal or high cobalamin values.

Conclusion. Patients with ACRC seem to have fairly adequate cobalamin and folate status before and during chemotherapy treatment. This study indicates that ACRC patients receiving chemotherapy do not need supplementation with vitamin B12 and folate. A minor portion of the patients had folate deficiency, and most of those patients had severe toxicity. Patients with subclinically low cobalamin values had surprisingly better survival.     

Incorporating Informatics for Integrating Biology and the Bedside (i2b2) into Predoctoral Trainee Curriculum to Evaluate Student‐Generated Hypotheses

As part of the Clinical and Translational Science Institute predoctoral TL1 training program at the Pennsylvania State University, a multidisciplinary team of predoctoral trainees representing the Chemistry, Neurosurgery, Nutritional Sciences, and Public Health Sciences departments were introduced to the NIH‐sponsored Informatics for Integrating Biology and the Bedside (i2b2) database to test the following student‐generated hypothesis: children with iron deficiency anemia (IDA) are at increased risk of attention deficit‐hyperactivity disorder (ADHD). Children aged 4–12 and 4–17 years were categorized into IDA and control groups. De‐identified medical records from the Penn State Milton S. Hershey Medical Center (HMC) and the Virginia Commonwealth University Medical Center (VCUMC) were used for the analysis. Overall, ADHD prevalence at each institution was lower than 2011 state estimates. There was a significant association between IDA and ADHD in the 4–17‐year‐old age group for all children (OR: 1.902 [95% CI: 1.363–2.656]), Caucasian children (OR: 1.802 [95% CI: 1.133–2.864]), and African American children (OR: 1.865 [95% CI: 1.152–3.021]). Clinical and Translational Science Award (CTSA) infrastructure is particularly useful for trainees to answer de novo scientific questions with minimal additional training and technical expertise. Moreover, projects can be expanded by collaborating within the CTSA network.     

Serum Vitamins D,B9 and B12 in Greek Patients with Inflammatory Bowel Diseases

Deficiencies in vitamin D, folate and cobalamin are common in Inflammatory Bowel Disease (IBD). The aim of the present study was to assess serum levels of these vitamins in IBD adults based on the respective serum cut off values for vitamin deficiencies, and to explore possible associations with IBD-related biomarkers and nutritional intake. A cross-sectional study was carried out and patients with Crohn’s disease (CD) or ulcerative colitis (UC) from Attica-Greece were enrolled. Medical and dietary history, clinical examination and blood/stool biomarkers were evaluated. In total, 87 patients participated in the study. Serum levels of 25(OH)D, folate and cobalamin were deficient in 36.8%, 18.4% and 5.7% of patients, respectively. Linear regression analysis in the overall patients showed positive associations between (a) serum 25(OH)D with serum iron (beta = 0.083, p = 0.005) and (b) serum cobalamin with total bilirubin (beta = 0.357, p = 0.020) and direct bilirubin (beta = 0.727, p = 0.033), adjusting for age, sex, body mass index (BMI), disease activity and duration, smoking, nutritional intake and season of recruitment. In CD patients (N = 54), a negative linear association between serum folate and fecal lysozyme was evident (beta = −0.009, p = 0.020). No associations were found for UC patients (N = 33). The serum vitamin profile may be a complementary biomarker for the evaluation of disease activity next to serum and stool inflammatory biomarkers.     

Eighteen-year follow-up of a patient with cobalamin F disease (cblF): report and review

Cobalamin F disease (cblF) is a rare disorder of intracellular cobalamin metabolism resulting in failure to thrive, recurrent stomatitis, skin rash, megaloblastic anemia, hypotonia, seizures, and intellectual disability. Data on long-term outcomes are not available. We report on the outcome of a patient with cblF disease with a frameshift mutation in the LMBRD1 gene after 18 years of intramuscular hydroxycobalamin treatment.