Cobalamin Injections Research Articles

Vitamin B group levels and supplementations in dermatology.

Irregularities of vitamin levels are being increasingly identified associated with skin conditions, and systemic and topical therapies have shown promising improvements. There have been some remarkable improvements achieved, but large variations in outcomes suggest that these conditions are not simply related to a single deficiency or solved by providing a single supplement. Cyanocobalamin, pyridoxine (B6) and riboflavin (B2) supplementation were linked with exacerbating existing acne. There were also reports of allergic reactions to parenteral cobalamin including acne, rosacea, allergic site reactions or anaphylaxis with cobalamin injections. This was also reported in patients who had allergic contact dermatitis to cobalt, where cobalamin therapy resulted in cutaneous manifestations such as chronic vesicular hand dermatitis, cheilitis and stomatitis. The use of niacinamide in acne vulgaris as an alternative to clindamycin or adjunct is also notable, as well as its application for hyperpigmentation. Vitamin B3 also has promise in chemoprevention in particular nonmelanoma skin cancer prophylaxis. Folic acid has a developing role in psoriasis. The data for vitiligo remains inconclusive. Assessment for potential vitamin deficiency, particularly B vitamins, should form part of the normal work-up for a wide range of skin conditions.

Falsely “high” serum cobalamin level in subacute combined degeneration of spinal cord secondary to pernicious anemia masquerading as myelodysplastic syndrome

AbstractCobalamin deficiency causes clinical manifestations ranging from anemia to neuropsychiatric presentations. We present a patient initially treated as myelodysplastic syndrome (MDS), who was later diagnosed to have pernicious anemia. He presented with pancytopenia, and bone marrow aspirate was suggestive of MDS. Serum cobalamin was high. Six months later, he developed progressive lower limb weakness. Magnetic resonance imaging (MRI) of the spine showed a hyperintense signal in the lateral aspects of the cord at C6 to T10 suggestive of subacute combined degeneration of the spinal cord. Homocysteine, methylmalonic acid, and anti‐intrinsic factor levels were found to be high, confirming the diagnosis of cobalamin deficiency secondary to pernicious anemia. His pancytopenia and weakness improved markedly after 5 months of parenteral cobalamin injection. This case highlights that cobalamin deficiency can mimic MDS, and second‐line assays are important in a patient with a high clinical suspicion of cobalamin deficiency despite normal serum cobalamin level.

Oral administration of cyanocobalamin for functional vitamin В<sub>12</sub> deficiency: efficacy and safety

The prevalence of vitamin В12deficiency is about 3—16% in the general population, while in older people, it ranges from 10 to 20%. An increase in the proportion of people on reduced-calorie diets, the widespread use of drugs that can result in vitamin В12deficiency, an increase in life expectancy, on the one hand, a variety of clinical manifestations and the lack of precise algorithms for laboratory diagnostics, on the other hand, suggest that the number of patients with vitamin В12deficiency is significantly higher. Vitamin В12can be absorbed by passive diffusion, regardless of intrinsic factor and other underlying causes of the deficiency. The presence of an additional route of absorption brings in new expectations for the oral administration of cyanocobalamin in therapeutic doses. Comparative clinical trials of the use of cyanocobalamin have shown that the oral route of administration is as effective as the parenteral. Considering the need for long-term, and in some cases — life-long, use of the drug, there is a need to develop dosage regimens for oral administration comparable in effectiveness to parenteral administration. The use of functional vitamin В12deficiency biomarkers, such as vitamin В12levels, cholotranscobalamin, methylmalonic acid, homocysteine, made it possible to establish that a daily dose of 1000 mkg is the most effective, which at the initial stage is as efficient as intramuscular administration. In some circumstances, maintenance therapy (intramuscularly at a dose of 1 mg/month) was more effective; thus, a differentiated approach scheme to determining the maintenance oral dose was proposed, depending on the result obtained at the initial stage of therapy. Comparative studies covering the entire spectrum from the recommended dietary allowance to the dose commonly used for cobalamin injections have shown that an oral daily dose of 1000 mcg of cyanocobalamin normalizes serum vitamin В12levels and causes an 80—90% decrease in plasma methylmalonic acid concentration from the assumed maximum value. The oral route of administration provides a higher patient treatment adherence.

Analysis of 70 patients with hydrocephalus due to cobalamin C deficiency.

To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalamin C (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients. A total of 1,211 patients were clinically diagnosed with methylmalonic acidemia (MMA) from 1998 to 2019. Among them, cblC deficiency was confirmed in 70 patients with hydrocephalus by brain imaging and biochemical and genetic analysis. Of the 70 patients, 67 (95.7%) had early-onset MMA and homocystinuria. The patients typically had high blood propionylcarnitine and total homocysteine, low methionine, and methylmalonic aciduria. Signs of intracranial hypertension were relatively rare. We measured ventricular dilatation early in the disease by cranial ultrasound and MRI and/or CT. Eighteen different MMACHC mutations, including 4 novel mutations (c.427C>T, c.568insT, c.599G>A, and c.615C>A), were identified biallelically in all 70 patients. c.609G>A was the most frequent mutation, followed by c.658_660del, c.217C>T, and c.567dupT. Three cases were diagnosed by postmortem study. Metabolic therapy, including cobalamin injections supplemented with oral l-carnitine and betaine, was administered in the remaining 67 cases. A ventriculoperitoneal shunt was performed in 36 cases. During the follow-up, psychomotor development, nystagmus, impaired vision, and sunset eyes improved gradually. Hydrocephalus is a severe condition with several different causes. In this study, ventriculomegaly was found in 70 patients with cblC deficiency. Early diagnosis, etiologic treatment, and prompt surgical intervention are crucial to improve the prognosis of patients.

Vitamin B12 deficiency as a cause of severe neurological symptoms in breast fed infant \u2013 a case report

BackgroundVitamin B12 (cobalamin, cbl) deficiency in children is rare and may occurs in exclusively breast fed infants of mothers on vegetarian or vegan diet with lack of appropriate supplementation. The clinical manifestation of vitamin B12 deficiency include neurological disorders, megaloblastic anemia and failure to thrive. Routine and commonly used laboratory tests such as cell blood count (CBC) or serum vitamin B12 level are sufficient for appropriate diagnosis. Typical therapy is based on intramuscular cobalamin injections. Early diagnosis and early onset of treatment are crucial factors for long-term prognosis of patients as the duration of deficiency may be correlated with the development of long lasting changes in the nervous system.The purpose of this article is to present influence of maternal vitamin B12 deficiency as a cause of infant psychomotor retardation.Case presentationWe report the case of a 7 months old girl whose parents sought medical advice due to pathological somnolence and developmental regression of their daughter with onset approximately 2 months prior to the visit. Following several diagnostic tests it was determined that the infant’s symptoms were due to vitamin B12 deficiency which was secondary to the mother’s latent Addison-Biermer disease. Apart from neurological symptoms the infant also showed megaloblastic anemia which is typical to cobalamin deficiencies. Intramuscular vitamin B12 supplementation resulted in instant improvement of the patient’s general condition and blood morphology. Unfortunately, psychological examination indicated long-term psychomotor retardation due to delayed diagnosis of B12 deficiency.ConclusionsVitamin B12 levels should be considered during differential diagnosis of neurological symptoms in exclusively breast-fed infants especially if they co-exist with megaloblastic anemia and psychomotor retardation.

Intranasal treatment of vitamin B12 deficiency in children

Vitamin B12 deficiency is traditionally treated with intramuscular injections of cobalamin, which are stressful events for children. In adults, studies have shown adequate absorption of intranasally administered vitamin B12. To date, data concerning efficacy of intranasal administration of vitamin B12 in children are lacking. We report on ten cases of children with vitamin B12 deficiency who were successfully treated with intranasal administration of a spray containing hydroxocobalamin. The mean baseline vitamin B12 concentration increased from 126.3 pmol/l (SD 55.4) to 1914.7 pmol/l (SD 1509.7). No side effects were reported.Conclusion: In children, intranasal application of vitamin B12 seems a safe and effective alternative to intramuscular injections, leading to higher compliance and less burden to patients.What is Known:• Children with vitamin B12deficiency are traditionally treated with intramuscular cobalamin injections, which are costly and painful.• Studies in adults showed that intranasal application of hydroxocobalamin leads to normalisation of vitamin B12levels.What is New:• The intranasal application of vitamin B12resulted in a substantial increase of the mean baseline vitamin B12levels without any side effect.• These data encourage a systematic evaluation of intranasal treatment of vitamin B12deficiency in order to define safety, optimal dosage and administration frequency.

WED 011 Subacute combined degeneration of the cord: laugh until you are weak

A 33 year old lady presented to her GP with a 2 week history of numbness affecting her thighs. Routine blood tests revealed normal haemoglobin and folate levels with a borderline B12 concentration of 103 ng/L. Over the subsequent 2 weeks the numbness spread to involve her feet and her hands. Despite commencing cobalamin injections her symptoms continued to progress. She was admitted to hospital 4 weeks after the onset of symptoms with disabling sensory ataxia.All reflexes were either absent or elicited only with reinforcement. Plantars were downgoing. There was impairment of all sensory modalities in a glove-and-stocking distribution, with proprioception accurate at the ankle on the right and the knee on the left. Her gait was broad-based. The remainder of the neurological examination was unremarkable.A full peripheral neuropathy screen revealed no abnormality. An MRI spine showed longitudinally extensive myelitis mainly affecting the dorsal cord extending from C4 to T3. MRI brain and lumbar puncture were pristine.Guided by the MRI findings direct questioning elicited a long history of frequent recreational nitrous oxide use. We review the accumulating literature regarding nitrous oxide-induced subacute combined degeneration of the cord and explore the pathophysiological mechanisms underlying it.

HEMATOLOGIC MANIFESTATIONS OF CROHN'S DISEASE: TWO CLINICAL CASES

Inflammatory bowel diseases (IBD) are commonly associated with extraintestinal manifestations, hematological disorders being the most special among them. In some cases, they dominate the clinical picture masking the intestinal manifestations of the underlying disease. Aplastic anemia is an extremely rare extraintestinal IBD manifestation. There are only two clinical cases of aplastic anemia associated with ulcerative colitis and non with Crohn's disease reported in the literature. Combination of Crohn's disease and В₁₂-deficient anemia is more prevalent, but is seen usually only after more than 20 cm of the ileus has been resected. The first clinical case presented in this paper is a combination of severe fistula-forming Crohn's disease with a constriction in the terminal part of the ileus and profound pancytopenia as an outcome of aplastic anemia. This profound pancytopenia is associated with an extremely high risk of life-threatening complications both of surgical treatment, as well as of several chemotherapeutic agents, which made the management of this patient difficult. The second clinical case demonstrates the manifestation of Crohn's disease as ileocolitis starting from the symptoms of cobalamin deficiency: severe В₁₂-deficient anemia, funicular myelosis and sensory ataxia, with blunted intestinal symptoms. This made the initial diagnosis and timely treatment difficult. Replacement therapy with cobalamin injections and treatment with glucocorticoids and antibacterials led to endoscopically confirmed remission of Crohn's disease and normalization of hematological parameters, with persistent polyneuropathy. Thus, management of patients with Crohn's disease should be multidisciplinary. In the case of anemia, leucopenia and/or thrombocytopenia in IBD patients it is necessary to exclude potential myelodysplasia and bone marrow aplasia. In the event of megaloblastic anemia and/or progressive polyneuropathy one should bear in mind potential cobalamin deficiency. However, in severe anemia it is important to perform diagnostic assessment for IBD, first of all, for Crohn's disease, especially, if any intestinal symptoms are present.

Review of oral vitamin B12 (cobalamin) therapy

<p>Vitamin B12 (cobalamin) deficiency is particularly common in adults and elderlies (>15%). Management of cobalamin deficiency with cobalamin injections is currently well codified, but new routes of vitamin B12 administration (oral and nasal) are being studied, especially oral vitamin B12 therapy for food-cobalamin malabsorption. Three prospective randomized studies, a systematic review by the <em>Cochrane</em> group and five prospective cohort studies were found and provide evidence that oral vitamin B12 treatment may adequately treat cobalamin deficiency. The efficacy was particularly highlighted when looking at the marked improvement in serum vitamin B12 levels and hematological parameters, for example hemoglobin level, mean erythrocyte cell volume, reticulocyte count. The effect of oral cobalamin treatment in patients presenting with severe neurological manifestations has not yet been adequately documented. Oral cobalamin treatment <ins cite="mailto:Nosaltres" datetime="2007-02-07T00:39">avoid</ins>s<ins cite="mailto:Nosaltres" datetime="2007-02-07T00:39"> the discomfort, inconvenience and cost of monthly injections</ins>.</p>

46. The First Viable Mouse Model of cblC Type Combined Methylmalonic Acidemia and Homocysteinemia: AAV Gene Therapy Rescues Neonatal Lethality and Provides Insight into Disease-Associated Retinal Degeneration

Combined methylmalonic acidemia and homocysteinemia, cblC type (cblC), is the most common inborn error of cobalamin metabolism and is caused by mutations in the MMACHC gene. MMACHC transports and processes intracellular cobalamin (vitamin B12) into its two active cofactors, 5’-adenosylcobalamin and methylcobalamin, necessary for the enzymatic reactions of methylmalonyl-CoA mutase and methionine synthase, respectively. Mutations in MMACHC result in methylmalonic acidemia, hyperhomocysteinemia and hypomethioninemia. Disease manifestations include growth failure, anemia, heart defects, developmental delay and a progressive maculopathy and pigmentary retinopathy that causes blindness, usually by the end of the first decade. Despite the use of conventional therapies including cobalamin injections and other cofactors, the manifestions of cblC, in particular the eye disease, remain unresolved with treatment. In order to explore disease pathophysiology and develop AAV gene therapy for cblC deficiency, we first created a viable mouse model using TALENs to edit the murine Mmachc gene, near the location of the most common mutation in humans, c. 271dupA. Two alleles were investigated: c. 165_166delAC p. P56CfsX4 (Δ2) and c. 162_164delCAC p. S54_T55delinsR (Δ3). MmachcΔ2/Δ3 and MmachcΔ3/Δ3 homozygous mutant mice displayed reduced survival, severe growth retardation, and massive metabolic perturbations. The median survival was less than 7 days with 90% of the mutant mice perishing before 3 weeks (Δ2 n=13; Δ3 n=42). The weights of MmachcΔ3/Δ3 mice were reduced relative to heterozygote and wild type littermates (n=15, p<0.0001). MmachcΔ2/Δ2 and MmachcΔ3/Δ3 mice (n=4, n=6) recapitulated the biochemical features of cblC, with significantly elevated plasma methylmalonic acid, homocysteine, cystathionine and decreased methionine compared to littermate controls (n=7) (p<0.05 for all metabolites). To assess the potential for gene therapy as a treatment for cblC, we generated two AAV vectors: rAAVrh10-CBA-mMmachc and rAAV9-CBA-hMMACHC and compared AAV with biweekly injections of OH-cobalamin, the standard therapy. MmachcΔ3/Δ3 mice were then treated with a single vector dose (1 × 1011 GC) delivered via intrahepatic injection in the neonatal period. MmachcΔ3/Δ3 mice treated with AAV vectors (AAVrh10 n=11, AAV9 n=5) displayed dramatically improved clinical appearance with improved growth (p= 0.0568), and increased survival (p<0.0001 for both vectors), with the oldest treated mutants currently living beyond 9 months. Successful gene therapy in the MmachcΔ3/Δ3 mice also enabled us to model, for the first time, cblC associated ocular pathology: surviving MmachcΔ3/Δ3 mice displayed thinning of the outer nuclear layer and shortening of photoreceptor outer segments, consistent with the pathology described in patients. Our results demonstrate that AAV gene delivery of MMACHC represents a new therapy for cblC which can treat the systemic, and possibly ocular, manifestations of this relatively common and devastating inborn error of metabolism.

A review of vitamin B12 in dermatology.

Vitamin B12, also known as cobalamin, is a water-soluble vitamin that is important in the hematological and nervous systems, and it has a complex relationship with the skin. Altered cobalamin levels can lead to dermatological manifestations, which may indicate a deficiency or excess of this vitamin. The biochemistry and metabolism of cobalamin is complex, and diseases can be associated with alterations of this metabolic pathway. The cutaneous manifestations of cobalamin deficiency include hyperpigmentation (most commonly); hair and nail changes; and oral changes, including glossitis. Additionally, several dermatologic conditions, including vitiligo, aphthous stomatitis, atopic dermatitis, and acne are related to cobalamin excess or deficiency. The cutaneous complications of cobalamin therapy include acne, rosacea, and allergic site reactions, or anaphylaxis with cobalamin injections. As cobalt is a component of cobalamin, patients with cobalt sensitivity have been reported to have cutaneous manifestations when receiving cobalamin replacement therapy.

Central Nervous System Complication due to Pernicious Anemia in a Patient with Rheumatoid Arthritis

Pernicious anemia (PA) is an autoimmune disease characterized by atrophic gastritis and deficiency in intrinsic factor leading to impairment of vitamin B12 absorption in the ileum. Anemia is commonly found in rheumatoid arthritis (RA); however, PA is rarely found in RA. There are few reports describing patients with both conditions; none in Korea to date. We report on a case of a 46-year-old female who presented with hypesthesia and general weakness. She was previously diagnosed as seropositive RA with myelodysplastic syndrome. She had severely impaired sensation, especially for vibration and proprioception in all limbs. Subacute combined degeneration was observed on her magnetic resonance imaging and serum vitamin B12 level was very low. Further exam results were consistent with PA and her symptoms improved with cobalamin injection. This case demonstrates that PA should be considered in RA patients presenting with both central nervous system manifestations and anemia. (J Rheum Dis 2015;22:327-331)

Transcutaneous electrical nerve stimulation in combination with cobalamin injection for post-herpetic neuralgia: A single-center randomized controlled trial

Transcutaneous electrical nerve stimulation in combination with cobalamin injection for post-herpetic neuralgia: A single-center randomized controlled trial

Transcutaneous Electrical Nerve Stimulation in Combination with Cobalamin Injection for Postherpetic Neuralgia

The aim of this study was to explore the efficacy of transcutaneous electrical nerve stimulation (TENS) with locally injected cobalamin in relieving pain and improving activities of daily living in patients with postherpetic neuralgia. Ninety patients (≥50 yrs old) with postherpetic neuralgia with a pain score of 4 or greater were randomized to receive TENS and local injections of cobalamin or lidocaine or a combination of cobalamin and lidocaine for 8 wks. Treatment efficacy was assessed on the basis of worst pain severity, global impression of change, activities of daily living, and quality-of-life. Time × group interaction, group differences, and time effect on worst pain at each follow-up point were statistically significant (P < 0.05) among the groups. In the group receiving TENS and local injection of cobalamin and in the group receiving TENS with a combination of cobalamin and lidocaine, the mean ± SD pain scores were 4.0 ± 1.4 and 4.1 ± 1.2 at endpoint, 28 and 26 patients achieved pain reduction of 30% or greater, and 14 and 10 perceived worst pain of 3 or less, respectively. The activities of daily living and quality-of-life data at the study endpoint showed significant benefits in the group receiving TENS and local injection of cobalamin and in the group receiving TENS and a combination of cobalamin and lidocaine (P < 0.05). In the group receiving TENS and local injection of lidocaine, the mean ± SD pain score was 6.1 ± 1.2 at the endpoint relative to baseline (P < 0.05), and only six patients achieved pain reduction of 30% or greater. TENS in combination with local cobalamin injection has a significant analgesic effect.

Effect of Administration Route on the Pharmacokinetics of Cobalamin in Elderly Patients: A Randomized Controlled Trial

BackgroundThe gold standard for cobalamin deficiency treatment is administration of cobalamin by intramuscular injection. The injection is painful and inconvenient, particularly for elderly persons. Cobalamin might also be administered intranasally. Previous studies do not provide insight into the pharmacokinetics of intranasal cobalamin administration in comparison with cobalamin injection. AimTo quantify the pharmacokinetics of intranasally and intramuscularly administered cobalamin to determine if intranasal administration might be an alternative for intramuscular administration. MethodsTen inpatients and outpatients of a geriatrics unit were recruited and randomly assigned to receive a single dose of 1000 μg cobalamin administered either by intranasal spray or intramuscular injection (5 per group). Inclusion criteria were written informed consent, age >65 years, and a cobalamin serum concentration <200 pmol/L. Total cobalamin serum concentrations were determined 10 times within 48 hours after administration. The differences in Cmax, Tmax, and AUC0–48h per administration route were statistically compared using ANOVA. ResultsThe average Cmax was 1 nmol/L after intranasal and 38.5 nmol/L after intramuscular administration. The average Tmax for intranasal and intramuscular administration was 42 minutes versus 342 minutes, respectively, and the AUC0–48 h was 1.3µmol/L/min versus 45.4µmol/L/min, respectively. These values also differed significantly (P<0.05). The estimated bioavailability of the intranasal administration was 2%. ConclusionsThe pharmacokinetics of intranasal and intramuscular cobalamin administration in elderly, cobalamin-deficient patients differ significantly. However, the estimated 2% bioavailability of cobalamin after intranasal administration makes intranasal cobalamin administration a potentially interesting administration route for elderly patients. Netherlands Trial Registry identifier: NTR 3005.

Early Biochemical and Hematological Response to Intramuscular Cyanocobalamin Therapy in Vitamin B12-Deficient Patients

Background: Data on early biochemical and hematological responses to cobalamin therapy in vitamin B₁₂-deficient patients are scarce. Therefore, we investigated whether cobalamin injections would include prompt biochemical and hematological responses in vitamin B₁₂-deficient patients. Subjects and Methods: Seven female patients (mean age: 69.4 years, range: 61-78) with a mean serum cobalamin level of 104 ± 38 pmol/l mean ± SD and 7 male patients (mean age: 67.0 years, range: 53-78) with a mean serum cobalamin level of 84 ± 40 (±SD) participated in the study. They were administered 1 mg i.m. cyanocobalamin per week for 3 weeks. Blood samples were collected before and 1, 3, 7, 14 and 21 days after cobalamin injection. The concentrations of plasma aminothiols and serum methylmalonic acid (MMA) were measured with high-performance liquid chromatography and gas chromatography/mass spectrometry, respectively, and hematological parameters were determined with a hematological analyzer. Results: Already 1 day after intramuscular Cobalamin injections, the concentrations of serum vitamin B₁₂ and plasma total cysteine were significantly increased while the concentrations of serum folate, plasma total homocysteine and serum MMA were decreased. Mean cell volume was also significantly decreased first after 14 days of therapy. Conclusion: Intramuscular cobalamin administration causes swift and significant changes in plasma aminothiols, whereas the first change in hematological parameters was detected only after 14 days.

悪性貧血に対し，経口的ビタミンB&lt;sub&gt;12&lt;/sub&gt;投与が著効した橋本病合併高齢者糖尿病の1例

A 73-year-old Japanese man with Hashimoto's disease and diabetes mellitus received regular medical checkups for type 2 diabetes care. Blood tests indicated macrocytic anemia (red blood cell count, 279×104 /μL; hemoglobin, 12.2 g/dL; hematocrit, 34.0%; mean corpuscular volume, 121.9 fL). The laboratory data demonstrated a normal folic acid level with a low vitamin B12 level. An endoscopic examination indicated no signs of gastric or intestinal bleeding. Positive results for anti-intrinsic factor antibodies were strongly suggestive of pernicious anemia. The patient refused cobalamin injections to treat the anemia. However, the oral administration of mecobalamin for the treatment of diabetic neuropathy was simultaneously initiated. Subsequently, the anemia gradually improved. Oral mecobalamin was presumably effective for pernicious anemia management. Anemia is frequently observed in elderly patients, and the incidence of pernicious anemia increases with age. Anemia is conventionally treated with cobalamin injections. Currently, the oral administration of mecobalamin is not the typical treatment for anemia. However, as in our case, a few reports have documented positive results following oral mecobalamin treatment. Moreover, oral mecobalamin is a fairly recent, novel, noninvasive mode of treatment, making it ideal for elderly patients, who are generally frail. This case suggests the efficacy of mecobalamin for the treatment of pernicious anemia.

Effect of administration route on the pharmacokinetics of cobalamin in elderly

ntroduction.– The standard treatment for cobalamin deficiency s supplementation by intramuscular injection. These injections, owever, are painful and inconvenient. It is thought that cobalmin can also be administered intranasally. Previous studies do ot provide insight in the pharmacokinetics in deficient elderly or in comparison with cobalamin injection. Here we aimed at uantifying the pharmacokinetics of intranasal and intramuscular dministered cobalamin in elderly cobalamin deficient patients. ethods.– Ten subjects were recruited and randomly divided nto two groups. A single dose of 1mg cobalamin was adminisered either by way of intranasal spray or intramuscular injection. nclusion criteria were written informed consent >65 years and obalamin serum concentration<200pmol/l. Total cobalamin erum concentrations were determined at ten different time interals. The average Tmax, Cmax, and AUC0–48 hours per administration oute were statistically compared with ANOVA. esults.– After intranasal cobalamin administration, the average max was 42minutes versus 342minutes for intramuscular adminstration. The average Cmax was 1040pmol/l versus 38486pmol/l, espectively. Due to the significant differences in Tmax andCmax, the UC0-48 hours also differed significantly between these two adminstration routes. iscussion and conclusion.– The pharmacokinetics of cobalamin fter intranasal and intramuscular administration differ signifiantly. Oral administration has been shown to be effective in the reatment of cobalamin deficiency. A Cmax comparable to the Cmax ound in this study after intranasal administration is reached after single oral dose of 1mg cobalamin. Therefore, further research n the safety, pharmacokinetics and efficacy of repeated intranasal obalamin administration is warranted. isclosure.– No significant relationships.

How can cobalamin injections be spaced in long-term therapy for inborn errors of vitamin B12 absorption?

Inborn errors of cobalamin (Cbl, vitamin B12) absorption include hereditary intrinsic factor deficiency (HIFD) and Imerslund–Gräsbeck disease (IGD). HIFD is secondary to mutations in the HIF gene while IGD is due to mutations in one of the 2 subunits of the intrinsic factor receptor that is cubilin (CUBN) or amnionless (AMN). These disorders lead to intracellular Cbl depletion which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid (MMA), and methionine depletion. The clinical presentation reflects Cbl deficiency, with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia. Mixed proteinuria, when it is present is strongly suggestive of IGD. Accurate diagnosis is always an emergency because early detection and treatment with life-long parenteral pharmacological doses of hydroxocobalamin are life saving and prevent further deterioration. However, the optimal frequency for cobalamin injections as a maintenance therapy is poorly reported. In order to evaluate the optimal maintenance schedule of cobalamin injections, we retrospectively collected clinical, biological, molecular and treatment data on 7 patients affected with congenital Cbl malabsorption. Unlike previous recommendations, we showed that a maintenance dosage of 1mg cobalamin twice a year was enough to ensure a normal clinical status and keep the hematological and metabolic parameters in the normal range. These data suggest that patients affected with inborn errors of cobalamin absorption may be safely long-term treated with cobalamin injections every 6months with careful follow-up of hematological and metabolic parameters. This maintenance regime is beneficial because the patients’ quality of life improves.

Involuntary movements after correction of vitamin B12 deficiency: a video‐case report

Involuntary movements can appear before and after initiation of vitamin B12 treatment. The pathogenesis of involuntary movements in vitamin B12 deficiency and their relationship with cobalamin injection remain unclear due to a lack of video-EEG documentation making the electroclinical correlation difficult to ascertain. Here, we report video-EEG and neuroimaging findings of an 11-month-old girl with vitamin B12 deficiency, who acutely developed involuntary movements a few days after initiation of vitamin B12 treatment with normal vitamin plasmatic levels. Abnormal movements were a combination of tremor and myoclonus involving the face, mouth, and left arm, which disappeared after discontinuation of therapy. [Published with video sequences].