Injections Of Hydroxocobalamin Research Articles

Vitamin B12 Deficiency-Induced Neuropathy and Cognitive and Motor Impairment in the Elderly: A Case Study.

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history.

Vitamin B12 Deficiency in Children and Adolescents: A Case for Revised Diagnostic Parameters.

Vitamin B12 deficiency is commonly diagnosed using thresholds developed for adults, yet emerging evidence indicates these levels may not be appropriate for children and adolescents. This misalignment can lead to underdiagnosis in younger populations, with potential long-term health implications. Chief Complaint: The 17-year-old female patient experienced severe fatigue, menstrual irregularities, psychological distress, and neurological symptoms over several years. The 13-year-old male patient had behavioral changes, gastrointestinal complaints, and sensory disturbances from an early age.Diagnosis: Both adolescents displayed B12 levels that were considered low-normal based on adult thresholds, complicating their diagnostic processes. Their diverse and atypical symptomatology required a comprehensive review of their medical and family histories, clinical symptoms, and risk factors.Intervention: Treatment included administration of hydroxocobalamin injections, complemented by dietary adjustments.Outcome: Both patients responded well to the treatment, showing significant improvements in their symptoms and overall quality of life. The main takeaway from these cases is the importance of tailoring diagnostic adequate thresholds and treatment plans to the pediatric population to address and manage B12 deficiency effectively. This approach can significantly enhance patient outcomes and prevent the progression of potentially severe complications in later life.

Vitamin B12 status in infancy and the effect of a vitamin B12 injection in infants with subclinical vitamin B12 deficiency: study protocol for a register-based randomised controlled trial

IntroductionVitamin B12 (cobalamin) is crucial for optimal child development and growth, yet deficiency is common worldwide. The aim of this study is twofold; (1) to describe vitamin B12 status and...

SUBACUTE COMBINED DEGENERATION OF THE SPINAL CORD SECONDARY TO NITROUS OXIDE-INDUCED B12 DEFICIENCY.

It is important to take a full history of illicit drug use, especially in young patients presenting with unusual symptoms.In cases of suspected nitrous oxide-induced neurological dysfunction with normal vitamin B12 levels, serum levels of methylmalonic acid and homocysteine can be measured to aid diagnosis.Prompt treatment of nitrous oxide-induced subacute combined degeneration of the spinal cord with B12 injections and discontinuation of nitrous oxide use allow for a gradual recovery, although in some cases patients may be left with residual symptoms.

Abnormal Movement Following Transcobalamin II Deficiency Treatment Responding to Clonazepam: A Case Report

AbstractTranscobalamin II (TCII) is a transporter protein that facilitates cobalamin release from the bloodstream to the cell. Deficiency in TCII is an autosomal recessive disorder caused by a mutation in the TCN2 gene. Treatment with intramuscular injection of hydroxocobalamin is greatly effective in improving the symptoms of this disorder. However, abnormal involuntary movements can occur and have been reported in patients with cobalamin deficiency caused by nutritional deficiency. Though, it is rarely associated with the treatment of hereditary TCII deficiency. Here, we report such a case, aiming to alert practitioners treating hereditary TCII deficiency. A 2-year-old boy born to a consanguineous parents presented with failure to thrive, recurrent infection, and pancytopenia. His condition deteriorated rapidly, and his investigation was remarkable for pancytopenia, elevated methylmalonic acid, and myelodysplastic changes in the bone marrow. A flash whole-exome sequence confirmed the diagnosis of TCII deficiency. The patient began treatment with IM hydroxocobalamin, and on the second day, he developed an abnormal involuntary movement that was abated by clonazepam. Abnormal nonepileptic movements following IM hydroxocobalamin in a patient with TCII deficiency shows a remarkable response to clonazepam.

Long-term outcome of a patient with Transcobalamin deficiency caused by the homozygous c.1115_1116delCA mutation in TCN2 gene: a case report

BackgroundTranscobalamin deficiency is a rare autosomal recessive inborn error of cobalamin transport (prevalence: < 1/1000000) which clinically manifests in early infancy.Case presentationWe describe the case of a 31 years old woman who at the age of 30 days presented with the classical clinical and laboratory signs of an inborn error of vitamin B12 metabolism. Family history revealed a sister who died at the age of 3 months with a similar clinical syndrome and with pancytopenia. She was started on empirical intramuscular (IM) cobalamin supplements (injections of hydroxocobalamin 1 mg/day for 1 week and then 1 mg twice a week) and several transfusions of washed and concentrated red blood cells. With these treatments a clear improvement in symptoms was observed, with the disappearance of vomiting, diarrhea and normalization of the full blood count. At 8 years of age injections were stopped for about two and a half months causing the appearance of pancytopenia. IM hydroxocobalamin was then restarted sine die. The definitive diagnosis could only be established at 29 years of age when a genetic evaluation revealed the homozygous c.1115_1116delCA mutation of TCN2 gene (p.Q373GfsX38).Currently she is healthy and she is taking 1 mg of IM hydroxocobalamin once a week.ConclusionsOur case report highlights that early detection of TC deficiency and early initiation of aggressive IM treatment is likely associated with disease control and an overall favorable outcome.

Efficacy of oral compared with intramuscular vitamin B-12 supplementation after Roux-en-Y gastric bypass: a randomized controlled trial

After Roux-en-Y gastric bypass (RYGB), patients often develop a vitamin B-12 deficiency. Our objective was to investigate whether oral supplementation increases and normalizes low vitamin B-12 concentrations (vitamin B-12>200 pmol/L) in RYGB patients as compared to intramuscular injections. A randomized controlled trial in RYGB patients with subnormal serum B-12 concentrations was performed. One group (IM B-12) received bimonthly intramuscular hydroxocobalamin injections (2000 µg as loading dose and 1000 µg at follow-up) for 6 mo. The second group (oral B-12) received daily doses of oral methylcobalamin (1000 µg). Serum vitamin B-12 was determined at baseline (T0) and at 2 (T1), 4 (T2), and 6 mo (T3) after start of treatment. Concentrations of the secondary markers methylmalonic acid (MMA) and homocysteine (Hcy) were measured at T0 and T3. Fifty patients were included and randomized, 27 in IM B-12 and 23 in oral B-12. The median vitamin B-12 concentration at T0 was 175 pmol/L (range: 114-196 pmol/L) for IM B-12 and 167 pmol/L (range: 129-199 pmol/L) for oral B-12. Vitamin B-12 normalized in all individuals, and there was no significant difference in vitamin B-12 between the two groups. MMA and Hcy concentrations decreased significantly after 6 mo within each group (P<0.001 and P<0.001 for MMA and P=0.03 and P=0.045 for Hcy, respectively). There was no significant difference between the groups at 6 mo for both MMA and Hcy (P=0.53 and P=0.79). The efficacy of oral vitamin B-12 supplementation was similar to that of hydroxocobalamin injections in the present study. Oral supplementation can be used as an alternative to hydroxocobalamin injections to treat RYGB patients with low values of serum vitamin B-12. This trial was registered at clinicaltrials.gov as NCT02270749.

Diagnosis &amp; Management of Vitamin B12 Deficiency in Primary Care – Are we following the guidelines?

Background: Vitamin B12 deficiency is common in primary care but its treatment practices vary across centres. One important cause of B12 deficiency is pernicious anaemia (identified by intrinsic factor antibodies), which is a risk factor for developing gastric carcinoma, and should be excluded. Additionally, recent evidence has suggested that some patients have been continued on B12 injections with no clear clinical indication. Recently,guidelines were produced to improve the investigation and management of B12 deficiency. Hence, this audit studied the investigation and management of B12 deficiency and adherence to clinical guidelines in a general practice (GP) in north-west England.Aim: To evaluate the appropriate diagnosis and management of vitamin B12 deficiency in our primary care centre against recognized standards.Methods: Clinical data of patients currently on oral cyanocobalamin and/or intramuscular hydroxocobalamin injections over a 1-year period were audited.Results: Thirty-eight patients (66% females, 34% males) receiving treatment for B12 deficiency were identified. Of these, 55% (21/38) had intrinsic factor antibodies checked and 52% (13/25) were managed according to the guidelines. 100% (8/8) of patients with dietary B12 deficiency (non-vegans) and 75% (3/4) of B12-deficient patients on long-term metformin have had follow-up serum B12 monitoring.Discussion: There is a need to improve the investigation for B12 deficiency, adherence to clinical guidelines, and documentation of patients’ diagnoses, treatment plans, dietary statuses, and required monitoring. We anticipate that adhering to guidelines when appropriate, with clear documentation, will improve the diagnosis and management of vitamin B12 deficiency so that safe prescribing and potential cost savings can be achieved.

Improving Bariatric Patient Aftercare Outcome by Improved Detection of a Functional Vitamin B12 Deficiency.

Vitamin B12 deficiency is common after bariatric surgery. Vitamin B12 is a poor predictor of functional vitamin B12 status, since deficiencies might even occur within the reference limits. Therefore, vitamin B12 deficiencies with serum vitamin B12 levels are between 140 and 200pmol/L remain undetected. Methylmalonic acid (MMA), however, will detect these deficiencies as accumulates due to functional intracellular vitamin B12 deficiencies. MMA is a relative expensive analysis and is therefore not generally available. To lower the costs, we only request MMA when vitamin B12 levels are between these levels. As a result, more biochemical deficiencies are found. However, it was not known whether bariatric patients with vitamin B12 levels between 140 and 200pmol/L would benefit from supplementation. Bariatric patients with vitamin B12 levels between 140 and 200pmol/L with (n = 45) and without (n = 45) intramuscular hydroxocobalamin injections were compared. Treated patients showed a significant increase of vitamin B12 levels (P < 0.001) and a significant decrease in MMA levels (P < 0.001). Biochemical improvement occurs in both patients with and without clinical symptoms. The control group showed a significant increase of MMA levels (P < 0.001). To examine whether biochemical benefits of vitamin B12 supplementation are correlated with clinical improvement, patient records were checked for complaints. Complaints were disappeared after treatment, while no improvement was seen in untreated patients. This study shows that all bariatric patients with vitamin B12 levels between 140 and 200pmol/L benefit clinical and biochemical from vitamin B12 supplementation, regardless the MMA levels.

Clinical, biochemical, and molecular analysis of combined methylmalonic acidemia and hyperhomocysteinemia (cblC type) in China

The most common inborn error of cobalamin (cbl) metabolism in China is the cblC type characterized by combined methylmalonic acidemia and hyperhomocysteinemia. The clinical presentation is relatively nonspecific, such as feeding difficulty, recurrent vomiting, hypotonia, lethargy, seizures, progressive developmental delay, and mental retardation, together with anemia and metabolic acidosis. More specific biochemical findings include high levels of propionylcarnitine (C3), free carnitine (C3/C0), and acetylcarnitine (C3/C2) measured by tandem mass spectrometry (MS/MS), elevation of methylmalonic acid (MMA) measured by gas chromatography-mass spectrometry (GC-MS), and increased total homocysteine with normal or decreased methionine. We report on 50 Chinese patients with combined methylmalonic acidemia and hyperhomocysteinemia. Forty-six belonged to the cblC complementation group. Mutation analysis of the MMACHC gene was performed to characterize the mutational spectrum of cblC deficiency, and 17 different mutations were found. Most were clustered in exons 3 and 4, accounting for 91.3% of all mutant alleles. Two mutations were novel, namely, c.315C>G (p.Y105X) and c.470G>C(p.W157S). In terms of genotype-phenotype correlation, the c.609G>A mutation was associated with early-onset disease when homozygous. Unlike previous reports from other populations, c.609G>A (p.W203X) was the most frequent cblC mutation detected in our study of Chinese patients, affecting 51 of 92 MMACHC alleles (55.4%). The high prevalence of this nonsense mutation could have potential therapeutic significance for Chinese cblC patients. Besides traditional approaches consisting of hydroxocobalamin injections, carnitine, betaine, and protein restriction, novel drugs that target premature termination codons may have a role in the future.

Severe pernicious anaemia in an 8-year-old African girl

An 8-year-old girl presented with severe muscular weakness, peripheral neuropathy, ataxia, fever and macrocytic anaemia. Clinically, vitamin B(12) (cobalamin) deficiency was considered. Despite the lack of pre-treatment laboratory confirmation of the diagnosis, a therapeutic trial of hydroxocobalamin injections was begun. After several days, a partial clinical response was seen. Within 5 months all symptoms had resolved. After treatment was initiated, laboratory analysis of pre-treatment blood samples confirmed the presence of vitamin B(12) deficiency. Auto-antibodies to intrinsic factor and parietal cells, pathognomonic for pernicious anaemia, were confirmed. Vitamin B(12) deficiency owing to dietary deficiency is not uncommon in children in developing countries. Although nutritional deficiency might have played a role in our patient, this case illustrates that the neurological manifestations of pernicious anaemia can present at a young age in African populations.

Oral or intramuscular vitamin B12?

Vitamin B12 deficiency is common, becoming more so with age, and estimates of its population prevalence have ranged from 1.5% to 15%.1,2 If untreated, it can lead to megaloblastic anaemia...

Reduced serum vitamin B12 levels during oral cyproterone-acetate and ethinyl-oestradiol therapy in women with diffuse androgen-dependent alopecia

In a group of healthy, non-vegetarian females currently being treated for diffuse androgen-dependent alopecia with 50 or 100 mg of oral cyproterone acetate for 11 days and 30 or 40 micrograms of ethinyl oestradiol for 20 days of the menstrual cycle, significant decreases in mean serum vitamin B12 (P less than 0.0001), haemoglobin (P less than 0.003) and haematocrit (P less than 0.004) values, were observed after 6 months. Serum folic acid, red-cell folate and mean cell volume remained unchanged within the normal range during this time. All patients responded to oral cyanocobalamin, or intramuscular injections of hydroxocobalamin. In patients with baseline serum vitamin B12 levels below 350 ng/l, we would suggest prophylactic cyanocobalamin concurrent with cyproterone-acetate-ethinyl-oestradiol (CPA EE2) therapy. Studies involving other dose regimens of CPA EE2 (Dianette) or cyproterone acetate alone (Androcur, Cyprostat), may require evaluation of the vitamin B12 status if treatment is to be given for periods of longer than 3 months.

Vitamin B-12: Placebo or neglected therapeutic tool?

Patients with normal serum vitamin B-12 levels were given injections of hydroxocobalamin (vitamin B-12b) interspersed with injections of sterile water. Those who felt better with B-12b had additional injections to establish the amount of B-12b that gave the maximum feeling of well-being. Serum vitamin B-12 tests were performed to record the level at which the patients felt best. On the same day they took a Multiphasic Personality Inventory (MMPI), an objective computerized psychological test. Hydroxocobalamin injections were then discontinued for 5 to 7 days. The patients took another serum vitamin B-12 test and another MMPI. With the higher vitamin B-12 levels, the MMPI patterns were at or closer to normal. With lower serum vitamin B-12 levels, MMPI patterns showed much more emotional distress. The author suspects that vitamin B-12 dependency disorders are common and are neglected by the medical profession.

A comparison of vitamin B12levels in the liver and serum of sheep receiving treatments used to correct cobalt deficiency

The efficacies of four methods, used for the prophylaxis of cobalt deficiency in sheep as measured by the elevation of liver and serum vitamin B12 levels, were compared in marginally deficient sheep over 14 weeks. The methods used were weekly drenches of either cobalt sulphate or cobalt chelate (EDTA) three-weekly injections of hydroxocobalamin, and ruminal cobalt pellets. On the basis of elevated liver and serum vitamin B12 levels, chelated cobalt was shown to be available to rumen microflora for the synthesis of vitamin B12. However, at no stage were liver and serum vitamin B12 levels of sheep receiving the chelate significantly different from those receiving the same amount of cobalt as the sulphate. After five, three-weekly injections of hydroxocabalamin liver vitamin B12 levels were significantly higher (p<0.01) than for the other treatments, with the exception of cobalt sulphate. Cobalt pellets led to an initial rapid and significant rise in serum vitamin B12 when compared with the other treatments. However, at four weeks there was no significant difference between treatment groups for serum vitamin B12. Fourteen weeks after the administration of cobalt pellets, serum and liver.vitamin B12 levels in this group were not significantly different from those of untreated sheep. At this time, three out of 12 sheep had lost their pellets.

Influence of Vitamin B-12 Status on Hepatic Propionic Acid Uptake in Sheep

Pregnant ewes were fed a depletion diet low in cobalt (0.06 ppm) for 3½ months: Chronic catheters were implanted 8 weeks postpartum and 7 experiments were performed on these nonlactating vitamin B-12-depleted sheep (de-B12: 340 ± 30 ng vitamin B-12 per gram wet liver) prior to repletion by intramuscular injection of hydroxocobalamin. Six experiments were then repeated after vitamin B-12 repletion (re-B12: 2220 ± 50 ng vitamin B-12 per gram wet liver). The hepatic extraction ratios (HER) in continuously fed sheep were 0.81 and 0.77 for de-B12 and re-B12 corresponding to net hepatic uptakes of 460 ± 50 and 440 ± 40 µmol propionate per minute, respectively. Continuous infusion of unlabeled propionate into a mesenteric vein at 1 mmol/minute reduced the HER, yet this depression was greatest for re-B12 (0.74 vs. 0.63 for de-B12 and re-B12, respectively). Net hepatic uptake of propionate was increased (1145 ± 100 vs. 985 ± 95 µmol/minute, respectively), although vitamin B-12 status was without effect. It is concluded that the ability of liver to extract propionate is not affected at vitamin B-12 concentrations greater than 250 ng/g wet liver. However, when propionate entry rate was enhanced by intramesenteric infusion, the livers of de-B12 sheep had a greater capacity to remove propionate suggesting that alternate routes of metabolism may occur.

Congenital Methylmalonic Aciduria-Homocystinuria With Megaloblastic Anemia: Observations on Response to Hydroxocobalamin and on the Effect of Homocysteine and Methionine on the Deoxyuridine Suppression Test

Congenital methylmalonic aciduria-homocystinuria, a disorder with an incompletely defined cobalamin abnormality, has not been accompanied by megaloblastosis in most of the initially described cases. This has raised questions about the exact role of cobalamin in relation to megaloblastic anemia. Therefore, we present our observations on a patient with this syndrome whose manifestations conformed to current concepts of cobalamin function and on her response to hydroxocobalamin. In addition to the megaloblastic anemia (and other hematologic abnormalities) she developed severe neurologic impairment shortly after birth. Hydroxocobalamin injections diminished her methylmalonic acid and homocys-tine excretion and corrected her megaloblastosis, though mild neutrophil nuclear hypersegmentation has persisted even after a year. Clinical status also improved, particularly physical growth and neurologic development. However, she remains neurologically impaired following an unexplained clinical catastrophe. We documented her megaloblastic process by demonstrating abnormal deoxyuridine suppression test results in her initial bone marrow aspirate and normal results after treatment. Furthermore, the abnormal deoxyuridine suppression was corrected in vitro by folic acid, but not by methyltetrahydrofolic acid, cyanocobalamin, adenosylcobalamin, methylcobalamin, or methionine. Homocysteine slightly worsened the deoxyuridine suppression pattern. Subsequent studies showed that, in contrast to previous reports, homocysteine had no beneficial effect in other normoblastic or megaloblastic marrows either. The findings in our patient are compatible with the “methyltetrahydrofolate trap” hypothesis. Why this syndrome presents such a wide spectrum of manifestations is not entirely clear, nor is it clear why it should differ so from other disorders of cobalamin. These aspects are reviewed. Severity of the defect, differences in tissue susceptibility, or possibly even other factors such as ability to retain cobalamin intracellularly may influence the manifestations of this metabolic disorder.

Tobacco amblyopia: the effect of treatment on the electroretinogram.

In seven recently diagnosed and untreated patients with tobacco amblyopia the light and dark adapted electroretionograms were recorded together with visual acuity, central fields and the Farnsworth-Munsell 100-Hue test. After 3 months treatment with injections of hydroxocobalamin all these tests were repeated. An improvement in visual acuity resulted in all cases. A significant reduction in the Farnsworth-Munsell total error score of the seven patients was noted (p less than 0.01). A significant increase in the amplitude of the light adapted b-wave of the ERG was found (0.01 less than p less than 0.02) following the course of hydroxocobalamin injections. No other significant changes in the ERG were demonstrated. It is suggested that the ERG changes demonstrated an improvement in an abnormal biochemical state in those bipolar and perhaps Müller cell of the inner nuclear layer of the retina which make electrophysiological connnections chiefly with foveal cones.

Interrelationships between the B-vitamins in B12-deficiency neuromyelopathy. A possible malabsorption-malnutrition syndrome

Five patients presenting clinically with a form B12-deficiency neuromyelopathy, with cord involvement in all and proximal muscle weakness in two of them, were investigated for their neurologic, hematologic and vitamin status. Megaloblastosis and achlorhydria were present in all, and impaired absorption of 57Co vitamin B12 and of D-xylose was detected in four. Total cyanide extracted vitamin B12 (A) was lowered in all cases and noncyanide extractable (B) in four of the five, being zero in three. All five responded to injections of hydroxocobalamin. In two patients sequential estimations showed that both A and B, especially the latter, rose steeply initially, normalizing at 50% of A after some weeks. Moiety B is suggested to be physiologically the more active and dissociable form of vitamin B12. Markedly elevated initial serum folate levels, and their subsequent fall under treatment with B12, indicated the operation of the "methyltetrahydrofolate trap". Blood levels of thiamin, nicotinic acid and pantothenic acid were within normal limits. However, serum riboflavin (B2) total vitamin B6 and pyridoxal were reduced in all where tested. Vitamin B6 deficiency could have resulted from its own malabsorption and have contributed to be B12 deficiency. Vitamin B2 and B6 levels also corrected themselves on B12 therapy. The B-vitamin deficiencies in our patients probably resulted from intestinal malabsorption, with a possible factor of malnutrition consequent to their strictly vegetarian diet.

The diagnosis and treatment of vitamin B12 deficiency in young lambs.

Abstract Extract In the course of some earlier experiments, it was observed that vitamin B12 deficiency in 2 hoggets was corrected by injection of hydroxocobalamin (vitamin B12b) (E. D. Andrews, pers. comm., 1972). Since this form of therapy offered a convenient and effective means of treating young lambs suffering from vitamin B12 deficiency, more detailed investigations were desirable. It has been known for some time that lambs on the cobalt-deficient area at the Ministry of Agriculture and Fisheries Kaitoke Farm lose condition after weaning. Abnormal amounts of methylmalonic acid (MMA) had been found in the urine of some of these lambs, indicating a state of vitamin B12 deficiency Andrews et al, (1970 Andrews, E. D., Hogan, K. G., Stephenson, B. J., White, D. A. and Elliott, D. C. 1970. Cobalt and thiabendazole live-weight responses in grazing sheep, and their relation to the urinary excretion of methylmalonic acid. N.Z. Jl agric. Res., 13: 950–965. [Taylor & Francis Online], [Web of Science ®] , [Google Scholar]).