ABSTRACT
BACKGROUND: 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. CASE SUMMARY: 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. CONCLUSION: 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.
Plain language titleRevisiting Diagnostic Criteria for Vitamin B12 Deficiency in Children and Adolescents, a Case ReportPlain language summaryVitamin B12 deficiency is surprisingly common in kids and teenagers, but the problem is, only adult standards are available to diagnose it. Research shows that healthy children can have much different B12 levels than adults, meaning some kids with a deficiency might not get the help they need quickly. We share stories of 2 teenagers who suffered from B12 deficiency with very different symptoms, from extreme tiredness to mood changes and stomach issues. These cases show that diagnosing B12 deficiency can be difficult, especially with symptoms that don't fit the usual pattern. However, once they were properly diagnosed and treated adequate, these young people saw significant improvements in their health. These cases highlight the need for new standards tailored to children, to better identify and treat B12 deficiency early on, improving their quality of life.
Subject(s)
Vitamin B 12 Deficiency , Vitamin B 12 , Humans , Vitamin B 12 Deficiency/diagnosis , Vitamin B 12 Deficiency/drug therapy , Adolescent , Female , Male , Vitamin B 12/administration & dosage , Vitamin B 12/blood , Vitamin B 12/therapeutic use , Hydroxocobalamin/therapeutic use , Hydroxocobalamin/administration & dosage , Quality of LifeABSTRACT
BACKGROUND: An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption. OBJECTIVE: This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency. METHODS: A narrative literature review of the diagnosis and treatment of vitamin B12 deficiency. RESULTS: Prevention and early treatment of B12 deficiency is essential to avoid irreversible neurological consequences. Diagnosis is often difficult due to diverse symptoms, marked differences in diagnostic assays' performance and the unreliability of second-line biomarkers, including holo-transcobalamin, methylmalonic acid and total homocysteine. Reduced dietary intake of B12 requires oral supplementation. In B12 malabsorption, oral supplementation is likely insufficient, and parenteral (i.e. intramuscular) supplementation is preferred. There is no consensus on the optimal long-term management of B12 deficiency with intramuscular therapy. According to the British National Formulary guidelines, many individuals with B12 deficiency due to malabsorption can be managed with 1000 µg intramuscular hydroxocobalamin once every two months after the initial loading. Long-term B12 supplementation is effective and safe, but responses to treatment may vary considerably. Clinical and patient experience strongly suggests that up to 50% of individuals require individualized injection regimens with more frequent administration, ranging from daily or twice weekly to every 2-4 weeks, to remain symptom-free and maintain a normal quality of life. 'Titration' of injection frequency based on measuring biomarkers such as serum B12 or MMA should not be practiced. There is currently no evidence to support that oral/sublingual supplementation can safely and effectively replace injections. CONCLUSIONS: This study highlights the interindividual differences in symptomatology and treatment of people with B12 deficiency. Treatment follows an individualized approach, based on the cause of the deficiency, and tailored to help someone to become and remain symptom-free.
Plain language titleDiagnosis and Treatment of Vitamin B12 DeficiencyPlain language summaryThe number of people who are at risk of developing a deficiency of vitamin B12 is steadily increasing. B12 deficiency can develop when people consume too few B12-containing foods of animal origin, or when they develop a form of B12 malabsorption. B12 deficiency can lead to serious complications so prevention and early treatment are essential. Diagnosing B12 deficiency can be challenging: the symptoms vary from patient to patient, and the methods used to measure B12 in the blood, or certain biomarkers associated with B12 metabolism, such as holo-transcobalamin, methylmalonic acid, and total homocysteine are unreliable. When people do not consume enough B12-containing foods, supplementation with B12 tablets is needed. In the case of B12 malabsorption, intramuscular injections of B12 are mandatory. The usual treatment with B12 is starting with injections of 1000 µg hydroxocobalamin twice weekly or on every other day for a period of up to 5 weeks or longer, until all symptoms have disappeared, and thereafter, the frequency of injections is gradually reduced. There is, however, a large group of people who require more frequent administration to become and remain symptom-free: this may range from daily or twice weekly to every 2 to 4 weeks.
Subject(s)
Dietary Supplements , Vitamin B 12 Deficiency , Vitamin B 12 , Vitamin B 12 Deficiency/diagnosis , Vitamin B 12 Deficiency/therapy , Vitamin B 12 Deficiency/drug therapy , Humans , Vitamin B 12/administration & dosage , Vitamin B 12/therapeutic use , Injections, Intramuscular , Biomarkers/blood , Methylmalonic Acid/blood , Hydroxocobalamin/therapeutic use , Hydroxocobalamin/administration & dosageABSTRACT
Mutations in MMACHC cause cobalamin C disease (cblC, OMIM 277400), the commonest inborn error of vitamin B12 metabolism. In cblC, deficient activation of cobalamin results in methylcobalamin and adenosylcobalamin deficiency, elevating methylmalonic acid (MMA) and total plasma homocysteine (tHcy). We retrospectively reviewed the medical files of seven cblC patients: three compound heterozygotes for the MMACHC (NM_015506.3) missense variant c.158T>C p.(Leu53Pro) in trans with the common pathogenic mutation c.271dupA (p.(Arg91Lysfs*14), "compounds"), and four c.271dupA homozygotes ("homozygotes"). Compounds receiving hydroxocobalamin intramuscular injection monotherapy had age-appropriate psychomotor performance and normal ophthalmological examinations. In contrast, c.271dupA homozygotes showed marked psychomotor retardation, retinopathy and feeding problems despite penta-therapy (hydroxocobalamin, betaine, folinic acid, l-carnitine and acetylsalicylic acid). Pretreatment levels of plasma and urine MMA and tHcy were higher in c.271dupA homozygotes than in compounds. Under treatment, levels of the compounds approached or entered the reference range but not those of c.271dupA homozygotes (tHcy: compounds 9.8-32.9 µM, homozygotes 41.6-106.8 (normal (N) < 14); plasma MMA: compounds 0.14-0.81 µM, homozygotes, 10.4-61 (N < 0.4); urine MMA: compounds 1.75-48 mmol/mol creatinine, homozygotes 143-493 (N < 10)). Patient skin fibroblasts all had low cobalamin uptake, but this was milder in compound cells. Also, the distribution pattern of cobalamin species was qualitatively different between cells from compounds and from homozygotes. Compared to the classic cblC phenotype presented by c.271dupA homozygous patients, c.[158T>C];[271dupA] compounds had mild clinical and biochemical phenotypes and responded strikingly to hydroxocobalamin monotherapy.
Subject(s)
Carrier Proteins , Hydroxocobalamin , Phenotype , Vitamin B 12 Deficiency , Vitamin B 12 , Humans , Hydroxocobalamin/administration & dosage , Hydroxocobalamin/therapeutic use , Male , Female , Vitamin B 12 Deficiency/genetics , Vitamin B 12 Deficiency/drug therapy , Vitamin B 12 Deficiency/blood , Vitamin B 12/blood , Child, Preschool , Carrier Proteins/genetics , Retrospective Studies , Oxidoreductases/genetics , Child , Methylmalonic Acid/blood , Homocystinuria/drug therapy , Homocystinuria/genetics , Infant , Mutation, Missense , Homozygote , Heterozygote , Homocysteine/blood , Adolescent , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acid Metabolism, Inborn Errors/drug therapy , Amino Acid Metabolism, Inborn Errors/blood , AdultABSTRACT
OBJECTIVES: Hydroxocobalamin (OHCob) is an antidote for cyanide poisoning in patients rescued from house fires and is known to cause interference with certain laboratory tests. Consensus is lacking on the extent of this interference and on how to handle these samples. The objectives of this study were to characterize OHCob interference across a wide range of laboratory tests and to develop protocols for identifying and reporting these samples. DESIGNS & METHODS: Patient plasma samples (n = 5) were spiked with OHCob (1.5 mg/mL) and compared to controls without this drug. A series of analytes were measured using chemistry, urinalysis, coagulation, hematology, and blood gas instruments. Dose-response testing was performed on a subset of assays that showed interferences ≥10%. RESULTS: Of the 77 analytes evaluated, 27 (35%) showed interference from OHCob, with chemistry and coagulation analytes showing the greatest effects. Of those affected, 22 analytes had a positive interference, whereas 5 analytes had negative interference. Dose-response studies showed dose-dependent increases and/or decreases consistent with initial spiking studies. Although red in colour, plasma samples with OHCob did not trigger hemolysis index flags, necessitating a special sample identification and reporting protocol. CONCLUSION: OHCob had significant effects on several analytes across different instruments. These findings led to the development of special sample handling and reporting protocols to identify OHCob samples and ensure only accurate results are released. It is vital for emergency departments to document and notify their laboratories whenever blood samples from these patients are drawn.
Subject(s)
Antidotes/pharmacokinetics , Blood Chemical Analysis , Hydroxocobalamin/pharmacokinetics , Poisoning , Potassium Cyanide , Antidotes/administration & dosage , Female , Humans , Hydroxocobalamin/administration & dosage , Male , Poisoning/blood , Poisoning/drug therapyABSTRACT
Objectives Transcobalamin II (TC) is an essential plasma protein for the absorption, transportation, and cellular uptake of cobalamin. TC deficiency presents in the first year of life with failure to thrive, hypotonia, lethargy, diarrhea, pallor, mucosal ulceration, anemia, pancytopenia, and agammaglobulinemia. Herein, we present TC deficiency diagnosed in two cases (twin siblings) with a novel variant in the TCN2 gene. Case presentation 4-month-old twins were admitted with fever, respiratory distress, vomiting, diarrhea, and failure to thrive. Physical examination findings revealed developmental delay and hypotonia with no head control, and laboratory findings were severe anemia, neutropenia, and hypogammaglobulinemia. Despite normal vitamin B12 and folate levels, homocysteine and urine methylmalonic acid levels were elevated in both patients. Bone marrow examinations revealed hypocellular bone marrow in both cases. The patients had novel pathogenic homozygous c.241C>T (p.Gln81Ter) variant in the TCN2 gene. In both cases, with intramuscular hydroxycobalamin therapy, laboratory parameters improved, and a successful clinical response was achieved. Conclusions In infants with pancytopenia, growth retardation, gastrointestinal manifestations, and immunodeficiency, the inborn error of cobalamin metabolism should be kept in mind. Early diagnosis and treatment are crucial for better clinical outcomes. What is new? In literature, to date, less than 50 cases with TC deficiency were identified. In this report, we presented twins with TCN2 gene mutation. Both patients emphasized that early and aggressive treatment is crucial for achieving optimal outcomes. In this report, we identified a novel variation in TCN2 gene.
Subject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Diseases in Twins/genetics , Transcobalamins/genetics , Amino Acid Metabolism, Inborn Errors/diagnosis , Amino Acid Metabolism, Inborn Errors/drug therapy , Codon, Nonsense/genetics , Consanguinity , Diseases in Twins/diagnosis , Diseases in Twins/drug therapy , Female , Homozygote , Humans , Hydroxocobalamin/administration & dosage , Infant , Injections, Intramuscular , Male , Pedigree , Polymorphism, Single Nucleotide , Transcobalamins/deficiency , Turkey , Twins, DizygoticABSTRACT
No disponible
Subject(s)
Humans , Female , Middle Aged , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/diagnosis , Anemia, Pernicious/complications , Anemia, Pernicious/diagnosis , Hydroxocobalamin/administration & dosage , Vitamin B Complex/administration & dosage , Mouth Diseases/etiology , Vitamin B 12 Deficiency/drug therapy , Anemia, Pernicious/drug therapyABSTRACT
INTRODUCTION: Methanethiol is a highly toxic chemical present in crude oil and natural gas. At high concentrations, methanethiol causes metabolic acidosis, seizures, myocardial infarction, coma, and death. Occupational Health and Safety Administration lists methanethiol as a potential terrorist weapon. Methanethiol blocks the electron transport chain, resulting in lactic acidosis and acidemia. There is no specific treatment for methanethiol. Our objective was to measure the efficacy of intravenous (IV) hydroxocobalamin (HOC) versus no treatment (control) in methanethiol-induced apnea in a swine model. METHODS: Sixteen anesthetized swine received IV sodium methanethiolate to apnea and were randomized to receive either IV HOC or no treatment. Physiologic and laboratory parameters were monitored throughout the study. Power analysis indicated that 8 animals per group would be sufficient to find a moderate effect (f = 0.24) with 2 groups, α = 0.05, and 80% power. RESULTS: Both groups were similar in baseline characteristics. Following treatment, the HOC group had significantly higher heart rate and blood pressure at 5-10 minutes post-apnea, higher systemic vascular resistance at 5 minutes post-apnea, higher tidal volume, higher end-tidal carbon dioxide, and lower end-tidal oxygen 10-15 minutes post-apnea compared with controls. None of the animals survived to the end of the study (60 minutes). The Kaplan-Meier survival curves were significantly different between cohorts (log-rank p = 0.0321), with the HOC group surviving longer than controls (32.4 ± 7.3 vs. 25.8 ± 1.0 minutes). CONCLUSIONS: In our model of intravenous methanethiolate poisoning, IV HOC administration resulted in a transient improvement in vital signs and prolonged time to death; however, it did not improve survival.
Subject(s)
Antidotes/administration & dosage , Apnea/drug therapy , Hydroxocobalamin/administration & dosage , Lung/drug effects , Sulfhydryl Compounds , Animals , Apnea/chemically induced , Apnea/physiopathology , Disease Models, Animal , Infusions, Intravenous , Lung/physiopathology , Sus scrofa , Time FactorsABSTRACT
A middle-aged patient presented with toxic inhalational injury, and was resuscitated prehospitally and treated in the emergency department for smoke inhalation, carbon monoxide (CO) exposure and cyanide poisoning with the use of antidotes. Due to the CO effects on spectrophotometry, an anaemia initially identified on blood gas analysis was thought to be artefactual, but was later confirmed by laboratory testing to be accurate. In addition, cyanide can confound haemoglobin testing due to its use in the analytical process and non-cyanide analysis is required when there is suspected exposure. Although no consensus exists on a first-line cyanide antidote choice, hydroxocobalamin is the only antidote without a serious side effect profile and/or deleterious cardiovascular effects. We propose prehospital enhanced care teams consider carrying hydroxocobalamin for early administration in toxic inhalational injury.
Subject(s)
Cyanides/poisoning , Smoke Inhalation Injury/complications , Administration, Intravenous , Antidotes/administration & dosage , Blood Gas Analysis , Carbon Monoxide Poisoning/complications , Fatal Outcome , Humans , Hydroxocobalamin/administration & dosage , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/etiology , Out-of-Hospital Cardiac Arrest/therapyABSTRACT
Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment.Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured.Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics.Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose.
Subject(s)
Antidotes/therapeutic use , Chelating Agents/therapeutic use , Cyanides/poisoning , Edetic Acid/therapeutic use , Hydroxocobalamin/therapeutic use , Animals , Cyanides/antagonists & inhibitors , Disease Models, Animal , Dose-Response Relationship, Drug , Edetic Acid/administration & dosage , Hydroxocobalamin/administration & dosage , Male , Pre-Exposure Prophylaxis/methods , Swine , Swine, MiniatureSubject(s)
Cobalt/blood , Hydroxocobalamin/adverse effects , Vasoplegia/blood , Biomarkers/blood , Cobalt/adverse effects , Humans , Hydroxocobalamin/administration & dosage , Male , Middle Aged , Vasoplegia/chemically induced , Vasoplegia/drug therapy , Vitamin B Complex/administration & dosage , Vitamin B Complex/adverse effectsABSTRACT
A 40-year-old male with alcoholic cirrhosis and end-stage renal disease presented for simultaneous liver and kidney transplantation. Hemodialysis was utilized intraoperatively during liver transplantation. During the procedure, the patient developed refractory hypotension and ultimately received hydroxocobalamin for vasoplegia. Shortly after administration, the hemodialysis machine ceased working after a "blood leak" alarm developed. Without the ability to continue intraoperative dialysis, the kidney transplantation portion of his surgery was postponed. The patient was transferred to the intensive care unit, where he underwent continuous renal replacement therapy overnight, and his kidney transplant proceeded the following morning.
Subject(s)
Hydroxocobalamin/administration & dosage , Renal Dialysis , Vasoplegia/drug therapy , Adult , Humans , Kidney Failure, Chronic/surgery , Kidney Transplantation , Liver Cirrhosis, Alcoholic/surgery , Liver Transplantation , MaleABSTRACT
An 18-year-old female patient presented to the emergency department with non-specific neurological and gastrointestinal symptoms and was found to be pancytopenic. Her vitamin B12 level was low with a normal mean corpuscular volume and her full blood count 2 months previously had been within normal range. She reported heavy use of nitrous oxide over the previous 2 weeks and other investigations revealed no cause for her pancytopenia. Her pancytopenia resolved with discontinuation of nitrous oxide and vitamin B12 treatment. Heavy use of nitrous oxide should be considered as a cause of pancytopenia.
Subject(s)
Nitrous Oxide/adverse effects , Pancytopenia/etiology , Vitamin B 12 Deficiency , Adolescent , Female , Humans , Hydroxocobalamin/administration & dosage , Hydroxocobalamin/therapeutic use , Vitamin B 12 Deficiency/chemically induced , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/drug therapyABSTRACT
OBJECTIVE: To compare the efficacy of methylene blue with combination therapy with hydroxocobalamin in patients experiencing vasoplegic syndrome after cardiac surgery. DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. PARTICIPANTS: Patients who received methylene blue with or without hydroxocobalamin for refractory vasoplegic syndrome rescue therapy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 0.the ability to maintain mean arterial pressure (MAP) >60 mmHg beyond 1hour after study drug administration. Other pertinent outcomes included MAP at hours 6, 12, and 24 post-administration; both raw and proportional changes of vasopressor doses from baseline at hours 1, 6, 12, and 24 post-administration; and change in pulmonary artery catheter hemodynamics. Overall, 28 doses were administered in 14 patients in the monotherapy group and 17 doses (10 methylene blue, 7 hydroxocobalamin) were administered in 6 patients in the combination therapy group. There were no differences in ability to maintain MAP at 1hour, with 71% of the monotherapy and 82% of combination therapy patients meeting MAP goals (pâ¯=â¯0.49). Pairwise comparisons demonstrated vasopressor reductions at 6, 12, and 24hours in both groups, but only significant reductions at 1hour were observed in the combination therapy group (-0.06 µg/kg/min; pâ¯=â¯0.003) but not in the monotherapy group (-0.015 µg/kg/min; pâ¯=â¯0.14). CONCLUSION: This is the first study to compare methylene blue monotherapy with combination therapy, which suggests there may be an advantage to combination therapy. Further characterization of ideal dosing, timing, and agent selection should be investigated on a larger scale format.