Low Serum Cobalamin Concentrations Research Articles

Serum cobalamin and methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or other acute enteropathies.

Low serum cobalamin concentrations have been associated with ileal malabsorption in dogs with chronic enteropathy. Increased serum methylmalonic acid (MMA) concentrations indicate cobalamin deficiency on a cellular level. Few studies have evaluated serum cobalamin concentrations or methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or nonparvoviral acute enteropathies. Evaluate serum cobalamin and methylmalonic acid concentrations in juvenile dogs (6 weeks to 10 months old) with parvoviral enteritis or nonparvoviral acute enteropathy. Thirty-one juvenile dogs with parvoviral enteritis, 29 dogs with nonparvoviral acute diarrhea (NPVAD), and 40 healthy juvenile control dogs. Single-center, prospective, observational, cross-sectional study. Serum cobalamin and, when sufficient serum was available, MMA concentrations were measured. Most serum cobalamin concentrations were within the adult reference interval. Serum cobalamin concentrations in healthy dogs (median, 848 ng/L; range, 293-1912 ng/L) were significantly higher than in dogs with parvoviral enteritis (P = .0002; median, 463 ng/L; range, <150-10 000 ng/L) or dogs with NPVAD (P = .02; median, 528 ng/L; range, 160-8998 ng/L). Serum MMA concentrations were not significantly different between groups (healthy dogs: median, 796 nmol/L; range, 427-1933 nmol/L; parvoviral enteritis: median, 858 nmol/L; range, 554-3424 nmol/L; NPVAD: median, 764 nmol/L; range, 392-1222 nmol/L; P = .1). Juvenile dogs with parvoviral enteritis or NPVAD had lower serum cobalamin concentrations than healthy juvenile dogs. However, based on serum MMA concentrations cellular cobalamin deficiency was not apparent.

Effects of oral cobalamin supplementation on serum cobalamin concentrations in dogs with exocrine pancreatic insufficiency: A pilot study

The objective of this retrospective study was to evaluate serum cobalamin concentrations before and after oral cobalamin supplementation in dogs with low serum cobalamin concentrations and exocrine pancreatic insufficiency (EPI). Eighteen dogs with serum trypsin-like immunoreactivities between <1.0−2.7 μg/L (reference interval, 5.2−35 μg/L) and serum cobalamin concentrations ≤350 ng/L (reference interval, 244–959 ng/L) were enrolled. All dogs were treated with oral cyanocobalamin according to a previously described protocol (0.25–1.0 mg daily, depending on bodyweight). Median (range) serum cobalamin concentrations at inclusion was 188 ng/L (<111−350 ng/L), which increased significantly to 1000 ng/L (794−2385 ng/L; P < 0.001) after cobalamin supplementation for 19−199 days (median, 41 days). Oral cobalamin supplementation is a potential alternative to parenteral supplementation in dogs with EPI.

Serum Cobalamin and Folate Concentrations in Common Marmosets (Callithrix jacchus) with Chronic Lymphocytic Enteritis.

Serum cobalamin and folate concentrations can serve as surrogate markers of gastrointestinal disease in dogs and cats, where they can have diagnostic, therapeutic, and prognostic implications. Chronic disease of the gastrointestinal tract, particularly chronic lymphocytic enteritis (CLE), occurs frequently in captive common marmosets. The aims of this study were to validate a commercially available assay for measuring serum cobalamin and folate concentrations in common marmosets, to establish reference intervals for these analytes in healthy marmosets, and to measure serum concentrations in common marmosets with CLE. The commercial assay was linear, accurate, precise, and reproducible for the measurement of serum cobalamin and folate concentrations in common marmosets. In healthy marmosets, the serum cobalamin concentration ranged from 322 to 2642 pg/mL (n = 35) and serum folate concentration from 54.8 to 786.4 ng/mL (n = 37). Low serum folate concentrations were moderately sensitive (greater than 70%) for CLE, and low serum cobalamin concentrations were moderately (greater than 70%) specific for CLE. Both serum cobalamin and folate concentrations were relatively unchanged in marmosets during 120 to 220 d. Serum cobalamin and folate concentrations were stable for approximately 7 y when samples were stored at -80 °C. Additional studies are warranted to further study the clinical implications of low serum cobalamin and folate concentrations in common marmosets.

Serum Cobalamin and Methylmalonic Acid Concentrations in Hyperthyroid Cats Before and After Radioiodine Treatment.

BackgroundHyperthyroidism, the most common endocrine disorder in cats, has been associated with low serum cobalamin concentrations. Whether this is a functional cobalamin deficiency of clinical importance has not been assessed.Hypothesis/ObjectivesCats with hyperthyroidism experience a functional cobalamin deficiency which correlates with their clinical catabolic state and is reversible with return of the euthyroid state.AnimalsThirty‐nine client‐owned hyperthyroid cats.MethodsProspective observational study. Serum cobalamin, methylmalonic acid, and clinical scores were determined in each hyperthyroid cat at enrollment and when euthyroid (60 days after radioiodine treatment).ResultsFive of the 39 hyperthyroid cats (13%) had a low serum cobalamin concentration ranging from <150 to 290 ng/L. Serum cobalamin concentrations normalized to >350 ng/L in 2 of the hypocobalaminemic cats once euthyroid. None of the hyperthyroid/hypocobalaminemic cats had increased serum methylmalonic acid concentrations (175–601 nmol/L). In cats with clinical and biochemical hyperthyroidism, there was no correlation between serum cobalamin concentrations with total T4 concentration (P = .12) or clinical scores including body weight (P = .11) and BCS (P = .54).Conclusions and Clinical ImportanceIn this population of hyperthyroid cats, the prevalence of hypocobalaminemia was low. Specifically, hyperthyroid cats, in which concurrent gastrointestinal disease is unlikely. Hypocobalaminemia is not a functional deficiency requiring supplementation in hyperthyroid cats without gastrointestinal disease.

Serum cobalamin concentrations in healthy cats and cats with non‐alimentary tract illness in Australia

To determine a reference range for serum cobalamin concentration in healthy cats in Australia using a chemiluminescent enzyme immunoassay and to prospectively investigate the prevalence of hypocobalaminaemia in cats with non-alimentary tract disease. Prospective study measuring serum cobalamin concentrations in clinically healthy cats and cats with non-alimentary tract illness. Blood was collected from 50 clinically healthy cats that were owned by staff and associates of Veterinary Specialist Services or were owned animals presented to Creek Road Cat Clinic for routine vaccination. Blood was collected from 47 cats with non-alimentary tract illness presented at either clinic. Serum cobalamin concentration was determined for each group using a chemiluminescent enzyme immunoassay. A reference range for Australian cats calculated using the central 95th percentile in the 50 clinically healthy cats was 345 to 3668 pg/mL. Median serum cobalamin concentration in 47 cats with non-alimentary tract illness (1186 pg/mL; range 117-3480) was not significantly different to the median serum cobalamin of the 50 healthy cats (1213 pg/mL, range 311-3688). Using the calculated reference range one sick cat with non-alimentary tract illness had a markedly low serum cobalamin concentration. Although hypocobalaminaemia is uncommon in sick cats with non-alimentary tract illness in Australia, its occurrence in this study warrants further investigation.

Relationships between Low Serum Cobalamin Concentrations and Methlymalonic Acidemia in Cats

Serum cobalamin concentrations below reference range are a common consequence of gastrointestinal disease in cats. Serum cobalamin <or= 100 ng/L is associated with methylmalonic acidemia. To determine the prevalence of cobalamin deficiency, defined by elevated serum methylmalonic acid (MMA), in cats with serum cobalamin <or= 290 ng/L, and the optimum serum cobalamin concentration to predict cobalamin deficiency in cats. SAMPLE SET: Residual serum samples (n = 206) from cats with serum cobalamin <or= 290 ng/L. Retrospective, observational study. Serum cobalamin and folate were measured with automated assays. Serum MMA was determined by gas chromatography-mass spectrometry. Cobalamin deficiency was defined as serum MMA > 867 nmol/L. Sensitivity and specificity of serum cobalamin concentrations <or=290 ng/L for detecting MMA > 867 nmol/L were analyzed using a receiver-operator characteristic curve. There was a negative correlation between serum cobalamin and MMA concentrations (Spearman's r=-0.74, P < 0.0001). The prevalence of MMA >or= 867 nmol/L in cats with serum cobalamin <or= 290 ng/L was 68.4%. Serum cobalamin <or= 160 ng/L had a 74% sensitivity and 80% specificity for detecting MMA > 867 nmol/L. No significant difference in serum folate concentrations was detected between affected and unaffected cats. Elevated MMA concentrations, suggesting cobalamin deficiency, are common in cats with serum cobalamin <or= 290 ng/L. Cobalamin deficiency is clinically significant, and supplementation with parenteral cobalamin is recommended for cats with gastrointestinal disease and low serum cobalamin concentrations.

Prevalence of cobalamin deficiency in Afyonkarahisar elderly population

Objectives To determine whether there was an increased prevalence of low serum cobalamin concentrations in elderly people. Design and Methods Serum concentrations of cobalamin were measured in 202 elderly people. Results In the elderly group, cobalamin concentrations less than 191 pg/mL were found in 79 subjects (39.1%) compared with 24.5% of 19–40 years old subjects (n = 527) and 29.7% of 41–64 years old subjects (n = 1100) (p Conclusion The prevalence of cobalamin deficiency was 39.1% in Afyonkarahisar elderly population. Many elderly people with low serum cobalamin concentration had not had hematological findings.

Outcome of cats with low-grade lymphocytic lymphoma: 41 cases (1995–2005)

To evaluate factors associated with response to treatment, remission duration, and survival in cats with low-grade lymphoma affecting various organ systems. Retrospective case series. 41 cats with histologically confirmed low-grade lymphocytic lymphoma. Medical records and biopsy specimens of cats with histologically confirmed low-grade lymphocytic lymphoma of various organ systems treated with prednisone and chlorambucil between 1995 and 2005 were reviewed. The Kaplan-Meier method was used to estimate remission duration and survival. Factors potentially associated with prognosis were compared. Common clinical signs were weight loss (83%), vomiting (73%), anorexia (66%), and diarrhea (58%). Seventy-eight percent of cats tested had low serum cobalamin concentrations. Lymphoma was confined to the gastrointestinal tract in 68% of cats. Fifty-six percent of cats achieved a complete response to treatment, and 39% achieved a partial response. Five percent of cats had no response. No association was found between any risk factors (including anatomic site) and response to treatment. Partial response was associated with shorter remission duration, compared with complete response; median remission duration was 428 days for cats achieving a partial response, compared with 897 days for cats achieving a complete response. No other factors were associated with remission duration. Overall median survival time was 704 days. No factors were significantly associated with survival time. Most cats with lymphocytic lymphoma responded to treatment with prednisone and chlorambucil, and most factors evaluated were not associated with outcome.

Hyperammonaemic encephalopathy secondary to selective cobalamin deficiency in a juvenile Border collie

An eight-month-old Border collie was presented with anorexia, cachexia, failure to thrive and stupor. Laboratory tests demonstrated a mild anaemia, neutropenia, proteinuria and hyperammonaemia. Serum bile acid concentrations were normal, but an ammonia tolerance test (ATT) was abnormal. The dog responded to symptomatic therapy for hepatoencephalopathy. When a low serum cobalamin (vitamin B12) concentration and methylmalonic aciduria were noted, the dog was given a supplement of parenteral cobalamin. Two weeks later, a repeat ATT was normal. Cobalamin supplementation was continued every two weeks, and all clinical signs, except for proteinuria, resolved despite withdrawing all therapy for hepatoencephalopathy. A presumptive diagnosis of hereditary selective cobalamin malabsorption was made, based on the young age, Border collie breed, low serum cobalamin concentration and methylmalonic aciduria. Although hereditary selective cobalamin malabsorption in Border collies, giant schnauzers, Australian shepherd dogs and beagles has previously been reported in North America, to the authors' knowledge this is the first report of the condition in the UK and the first to document an abnormal ATT in a cobalamin-deficient dog.

Supplementation with vitamin B 12 decreases homocysteine and methylmalonic acid but also serum folate in patients with end-stage renal disease

Hyperhomocysteinemia is frequently found in patients with end-stage renal disease (ESRD). Plasma total homocysteine (tHcy) concentrations may be reduced by supplementation with folic acid or combinations of folic acid, vitamin B 12, and vitamin B 6. Supplementation studies with vitamin B 12 alone in patients with ESRD have not yet been published. In this study, we investigated the effects of intravenous injection of cyanocobalamin (1 mg/wk for 4 weeks) in ESRD patients (N = 14) with low serum cobalamin concentrations (< 180 pmol/L). All patients had elevated levels of plasma tHcy, methylmalonic acid (MMA), and cystathionine before supplementation. After supplementation, plasma tHcy and MMA decreased 35% and 48%, respectively; however, cystathionine levels were unchanged. The extent of the plasma tHcy reduction tended to be influenced by the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR). Serum cobalamin increased significantly upon supplementation, whereas serum folate levels were substantially reduced by 47%. In contrast, red blood cell (RBC) folate was unchanged. This study shows that vitamin B 12 supplementation effectively decreases both MMA and plasma tHcy in ESRD patients with low B 12 levels. Furthermore, it illustrates the close interrelation between vitamin B 12 and folate metabolism.

Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations

To determine whether cerebrospinal fluid (CSF) methylmalonic acid (MMA) is increased in neurological patients with low serum cobalamin (Cbl, vitamin B12) concentrations as opposed to neurological patients with normal serum Cbl concentrations. We measured MMA concentrations in serum and CSF of neurological patients with low serum cobalamin concentrations, but without overt cobalamin related manifestations such as anemia or combined disease of the cord, and neurological patients with normal serum cobalamin concentrations (controls). Serum and CSF MMA concentrations were significantly higher in patients than in controls. Serum MMA was elevated in 4 patients of whom 3 had clearly elevated CSF MMA concentrations. Strong indications for cobalamin deficiency can be found not only in serum but also in CSF of patients with seemingly asymptomatic low serum cobalamin concentrations.

Small intestinal bacterial overgrowth in dogs with chronic intestinal disease

Summary Small intestinal bacterial overgrowth (sibo) was diagnosed by quantitative bacterial culture of duodenal juice samples obtained endoscopically in 41 of 80 dogs that were admitted with chronic diarrhea, vomiting, or weight loss. Thirteen dogs had aerobic bacterial overgrowth, most frequently comprising Escherichia coli, staphylococci, and enterococci, and 28 dogs had mixed anaerobic overgrowth, most frequently including Clostridium and Bacteroides spp. Affected dogs comprised 23 breeds, including 10 German Shepherd Dogs, and median age at diagnosis was 2 years (range, 6 months to 11 years). High serum folate and low serum cobalamin concentrations had fair specificity (79 and 87%, respectively), but low sensitivity (51 and 24%, respectively) in detecting sibo. Histologic examination of duodenal biopsy specimens did not reveal abnormalities (26/41 dogs), or revealed mild to moderate lymphocytic (12/41) or eosinophilic (2/41) infiltrates, or lymphosarcoma (1/41). Oral antibiotic treatment was effective in 77% (23/30 dogs), but prolonged treatment (&gt; 4 weeks) was required to control signs and prevent recurrence in 50% (15/30). Corticosteroids were used alone in a dog with eosinophilic enteritis and in combination with antibiotics in 4 dogs with marked gastrointestinal lymphocytic/plasmacytic infiltrates. This study suggested that sibo may be observed in dogs of many breeds, without an obvious primary cause, and that, although results of indirect tests may be suggestive of sibo, bacterial culture of duodenal juice samples remains necessary for definitive diagnosis.

Prevalence of cobalamin deficiency in the Framingham elderly population

To determine whether the increased prevalence of low serum cobalamin concentrations in elderly people represents true deficiency, serum concentrations of cobalamin and folate and of metabolites that are sensitive indicators of cobalamin deficiency were measured in 548 surviving members of the original Framingham Study cohort. Serum cobalamin concentrations < 258 pmol/L were found in 222 subjects (40.5%) compared with 17.9% of younger control subjects (P < 0.001). Serum methylmalonic acid and total homocysteine concentrations were markedly elevated in association with cobalamin values < 258 pmol/L in 11.3% and 5.7%, respectively, of the cohort. Both metabolites were increased in 3.8% of the cohort, associated with significantly lower erythrocyte counts and higher mean cell volumes. Serum metabolites correlated best with serum cobalamin values, even when subnormal determinations were excluded. The prevalence of cobalamin deficiency was > or = 12% in a large sample of free-living elderly Americans. Many elderly people with "normal" serum vitamin concentrations are metabolically deficient in cobalamin or folate.

Dementia patients with low serum cobalamin concentration: relationship to atrophic gastritis.

Serum concentrations of group I pepsinogens (pepsinogen-I) and gastrin were determined in patients with dementia disorders in order to assess the relationship, if any, between these indices of gastric mucosal function and serum cobalamin (vitamin B12) levels. A significant positive correlation between pepsinogen-I and B12 and, as expected, an inverse relationship between gastrin and pepsinogen-I concentrations was found, indicating that vitamin B12 deficiency was mainly determined by gastric mucosal atrophy (atrophic gastritis) in this West-Swedish sample of patients with dementia disorders. Patients with low B12 but normal gastrin and pepsinogen-I concentrations should, therefore, be further evaluated for possible nutritional deficiency, as well as nongastric causes of poor B12 assimilation from the diet.

Diagnosis of cobalamin deficiency I: Usefulness of serum methylmalonic acid and total homocysteine concentrations

The serum cobalamin assay is the primary diagnostic test for cobalamin deficiency. It appears to be an excellent screening test since most patients with clinically confirmed cobalamin deficiency have low levels. Recent studies indicate that the clinical picture of cobalamin deficiency is much more diverse than previously believed. It is also apparent that many patients with low serum cobalamin concentrations are not cobalamin deficient. Thus, there is a need for additional diagnostic tests to further distinguish patients with low serum cobalamin levels who are actually cobalamin deficient and will benefit from lifetime treatment from those who are not deficient and will not benefit. Serum levels of methylmalonic acid and total homocysteine have been shown to be markedly elevated in most patients with cobalamin deficiency, and total homocysteine concentrations are markedly elevated in most patients with folate deficiency. The levels of these metabolites fall to normal if these patients are treated with the appropriate vitamin but remain essentially unchanged if the wrong vitamin is administered. These observations demonstrate that serum methylmalonic acid and total homocysteine levels are useful in diagnosing patients with cobalamin and folate deficiency and in distinguishing between these two vitamin deficiencies.

Cyanocobalamin absorption in the elderly: results for healthy subjects and for subjects with low serum cobalamin concentration.

We examined the intestinal absorption of cyano[57Co]cobalamin from a non-protein-bound test dose given to 38 subjects from a population of elderly. The subjects were 76 years old and were apparently free from conditions known to affect cyanocobalamin absorption. Their gastric mucosal function was normal, as judged from determinations of serum gastrin and pepsinogen I. The urinary excretion of radioactivity during the first 24 h was 24(SD 7)%, range 8.6 to 45.2%, corresponding to a health-associated reference interval of 10 to 38%. The results indicate that cyanocobalamin absorption does not decline during normal aging. Duplicate studies were performed in another 20 subjects (70-81 years old) from the same population study; these subjects had a serum cobalamin concentration less than 130 pmol/L. The imprecision (CV) was 23%.