Vitamin B12 deficiency presenting as neck pain and cervical radiculopathy.

Vitamin B12 is required for the formation of haematopoietic cells and the synthesis of myelin. Deficiency typically presents with fatigue and megaloblastic anaemia. Prolonged deficiency can cause neurological symptoms such as paresthesia, which can progress to subacute combined degeneration of the spinal cord. We describe an unusual presentation of B12 deficiency in a young man who was initially diagnosed and treated for cervical radiculopathy. This case highlights the challenges of diagnosing B12 deficiency in patients with neurologic but without haematologic, abnormalities. While the current incidence of B12 deficiency in developed countries is low, cases are likely to rise with the increased adoption of veganism. Clinicians should be aware of the variable presentations of B12 deficiency because delayed diagnosis and treatment increases morbidity and can cause irreversible neurological deficits.

A new perspective on vitamin B12 deficiency in rheumatology: a case-based review.

Vitamin B12 (cobalamin) deficiency is common in patients with rheumatic diseases. Pernicious anemia is a well-known cause, but recent reports suggest that autoimmune-derived deficiency may not be limited to this cause alone. Symptoms of low vitamin B12 concentration are often deceptive, mimicking and overlapping with symptoms of other conditions. Neuropsychiatric manifestations, anemia, and fatigue are frequently attributed to a rheumatic disease without further evaluation. In this study, we present three cases of patients with neuropathic pain, depression, fatigue, and muscle weakness, initially attributed to a rheumatic disease, which almost completely resolved after implementing vitamin B12 supplementation. Furthermore, we provide an overview of current scientific reports regarding the potential use of cobalamin in rheumatology. Treatment of pain and neuropathy, often very challenging in long-lasting rheumatic diseases, can be more effective after a course of vitamin B12, even when no apparent deficiency is detected in laboratory tests. Considering recent research demonstrating vitamin B12's nerve-protecting properties, we recommend that physicians should assess vitamin B12 levels early in the diagnostic process of rheumatic diseases. In specific cases, physicians should consider cobalamin supplementation regardless of vitamin B12 serum concentration.

Vitamin B12 is associated negatively with anemia in older Chinese adults with a low dietary diversity level: evidence from the Healthy Ageing and Biomarkers Cohort Study (HABCS).

OBJECTIVE: The associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. METHODS: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia. RESULTS: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41). CONCLUSION: The relationship between vitamin B12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B12.

Not a Laughing Matter: When Nitrous Oxide Causes Functional Vitamin B12 Deficiency.

Subacute combined degeneration (SCD) is an acquired neurologic complication from prolonged vitamin B12 deficiency. As a result of dorsal and lateral spinal cord column degeneration, patients present with a range of neurological symptoms, including paresthesias, ataxia, and muscle weakness. Without prompt treatment, irreversible nerve damage occurs. Here we present a young man who developed progressive ascending paresthesias and lower extremity weakness after escalated nitrous oxide use. This case highlights the importance of considering SCD from nitrous oxide toxicity when patients present with progressive ataxia, paresthesia, and lower extremity weakness.

Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study.

BACKGROUND: The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD. METHODS: The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk. RESULTS: Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31-2.20) for all-cause mortality, and 2.00 (1.39-2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001). CONCLUSION: MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.

A New Case of Association of Megaloblastic Anemia and Pancytopenia of Infants.

BACKGROUND: Vitamin B12, or cobalamin deficiency, an infrequent clinical entity in pediatric age, is found almost solely in breastfed infants whose mothers are purely vegetarian, non-supplemented or with pernicious anemia. Megaloblastic anemia in infants presents with generalized weakness or irritability. METHODS: Diagnosis is usually centered on complete blood count, vitamin dosing, and peripheral smear, which may show macrocytes, hypersegmented neutrophils, reticulocytopenia and a raised mean corpuscular volume (MCV ˃ 100 fL). Pancytopenia has also been noted. RESULTS: We report an exclusive breastfed nine-month-old female child who presented with irritability, developmental delay, and difficulties in introducing new foods. Her initial blood count revealed pancytopenia. Vitamin B12 levels were found to be reduced. Maternal levels of Vitamin B12 were also found to be borderline low. The child was treated as per protocols, and improvement was evidenced with the return of hematological parameters to the regular and gradual advancement of milestones. CONCLUSIONS: We aim to underscore the importance of megaloblastic anemia as an important and rare cause of anemia in infancy.

Feline hyperammonemia associated with functional cobalamin deficiency: A case report.

Ammonia is a major neurotoxic substance associated with the complex pathogenesis of hepatic encephalopathy. Although several primary and secondary conditions have been reported to cause hyperammonemia, in veterinary medicine this condition is considered primarily associated with hepatic disease or portosystemic shunting. Only a few cases of inherited urea cycle enzyme deficiency and organic acid metabolic disorders have been reported in cats with hyperammonemia. To the best of our knowledge, this is the first report of hyperammonemia in a cat caused by accumulation of methylmalonic acid (MMA) secondary to functional cobalamin deficiency. A 2-year-old spayed female Turkish Angora cat exhibited postprandial depression with a 3-month history of hyperammonemia. Serum protein C and bile acid concentrations were normal. Plasma amino acid analysis revealed a deficiency of urea cycle amino acids. Although the serum cobalamin concentration was markedly high, there was no evidence of inflammatory, hepatic, or renal disease or neoplasia on blood, ultrasonographic, and computed tomographic examination. Gas chromatography-mass spectrometry revealed a high MMA concentration in the urine. Based on the results, functional cobalamin deficiency was diagnosed. Following oral amino acid supplementation and initiation of a low-protein diet, the serum ammonia level returned to normal and the postprandial depression improved. Urea cycle amino acid deficiency secondary to functional cobalamin deficiency presumably caused hyperammonemia due to MMA accumulation in this case.

Hyperammoniémie féline associée à un déficit fonctionnel en cobalamine : rapport de cas. L'ammoniac est une substance neurotoxique majeure associée à la pathogenèse complexe de l'encéphalopathie hépatique. Bien que plusieurs affections primaires et secondaires aient été signalées comme étant à l'origine d'une hyperammoniémie, en médecine vétérinaire, cette affection est considérée comme principalement associée à une maladie hépatique ou à un shunt porto-systémique. Seuls quelques cas de déficit héréditaire en enzymes du cycle de l'urée et de troubles métaboliques des acides organiques ont été signalés chez des chats atteints d'hyperammoniémie. À notre connaissance, il s'agit du premier rapport d'hyperammoniémie chez un chat causée par une accumulation d'acide méthylmalonique (MMA) secondaire à un déficit fonctionnel en cobalamine.Une chatte angora turque stérilisée âgée de 2 ans a présenté une dépression postprandiale avec une histoire d'hyperammoniémie depuis 3 mois. Les concentrations sériques de protéine C et d'acides biliaires étaient normales. L'analyse plasmatique des acides aminés a révélé une déficience en acides aminés du cycle de l'urée. Bien que la concentration sérique de cobalamine ait été nettement élevée, il n'y avait aucun signe de maladie inflammatoire, hépatique ou rénale ou de néoplasie à l'examen sanguin, échographique et tomodensitométrique. La chromatographie en phase gazeuse-spectrométrie de masse a révélé une forte concentration de MMA dans l'urine. Sur la base des résultats, un déficit fonctionnel en cobalamine a été diagnostiqué. Après une supplémentation orale en acides aminés et la mise en place d'un régime pauvre en protéines, le taux sérique d'ammoniac est revenu à la normale et la dépression postprandiale s'est améliorée. Une carence en acides aminés du cycle de l'urée secondaire à une carence en cobalamine fonctionnelle a vraisemblablement causé une hyperammoniémie due à l'accumulation de MMA dans ce cas.(Traduit par Dr Serge Messier).

Evaluation of the One-Hour ¹³C-Propionate Breath Test in 49 Patients from a Single Center in Japan to Detect Vitamin B12 Deficiency.

BACKGROUND Given the unavailability of reliable biomarkers for vitamin B12 (VB12) deficiency in clinical settings, the usefulness of the ¹³C-propionate breath test (PBT), utilizing VB12 as a coenzyme of methylmalonyl-CoA in propionate metabolism, as a diagnostic modality for VB12 deficiency has been studied. However, a collection time of 2 h reduces its convenience. Hence, we evaluated the effectiveness of 1-h PBT for detecting VB12 deficiency in 49 patients with suspected VB12 deficiency. MATERIAL AND METHODS We collected 100-200 mL breath gas every 10 min until 1 h after the administration of 1 g of ¹³C-propionate from 49 patients (31 men, 18 women; median age, 70 years) with clinically suspected VB12 deficiency and calculated the ¹³CO2 recovered in the breath per hour as the recovery rate (RR [%dose/h]) from ¹³CO2/¹²CO2 using infrared isotope spectrometry. We compared the RRs between groups: (1) with serum VB12 levels ≥145 pg/mL and <145 pg/mL, (2) with mean corpuscular volume ≤100 fL and >100 fL, and 3) pre- and post-VB12 supplementation. RESULTS The RRs peaked within 30 min. The RRs at 20 min (RR20) and 30 min (RR30) were significantly lower in macrocytotic patients (41.28 vs 50.07, p=0.026 and 37.82 vs 43.93, P=0.003). The RR30 was higher in the supplemented patients (41.93 vs 32.84, P=0.024). There was no significant difference in RRs between the patients with normal and low serum VB12 levels. CONCLUSIONS The 1-h PBT can be a diagnostic modality for VB12 deficiency because 1 h is a sufficient collection time.

Bilateral sixth nerve palsy with subdural hematoma: a unique presentation of B12 deficiency.

Vitamin B12 is inextricably associated with the development and maintenance of neuronal functions. It is classically associated with subacute combined degeneration and peripheral neuropathy; however, cranial neuropathy is uncommon. We observed the rarest neurological manifestation of B12 deficiency. A 12 months infant had history of lethargy, irritability, anorexia, paleness, vomiting, and neurodevelopmental delay for 2 months. He also developed inattention and altered sleep pattern. His mother noticed bilateral inward rotation of both eyes. On examination, the infant had bilateral lateral rectus palsy. The infant was found to have anemia (7.7g/dL) and severe B12 deficiency (74pg/mL). On MRI, there was cerebral atrophy, subdural hematoma (SDH) and wide cisternal spaces and sulci. On supplementation with cobalamin, he improved clinically though mild restriction of lateral gaze on the left side persists. Follow up MRI showed significant improvement in cerebral atrophy with resolution of SDH. To date, such clinical presentation of B12 deficiency has never been reported. The authors suggest B12 supplementation for at risk population esp at antenatal stage and lactating mothers in national programs. The treatment of this condition should be initiated early to prevent long term sequelae.

Determinants of vitamin B12 deficiency in patients with type-2 diabetes mellitus - A primary-care retrospective cohort study.

BACKGROUND: Like many developed nations, the prevalence of both older people and type-2 diabetes mellitus (T2DM) in Singapore is rising. This demographic shift predisposes the population to greater risks of both frailty and its complications that can be further aggravated by vitamin B12 deficiency -a highly prevalent associated variable that is potentially modifiable. Indeed, B12 deficiency adversely impacts the neuro-cognitive, haematological, and even the immune systems; jeopardizing our aspirations for successful aging. Despite this, many patients with T2DM in primary care remain unscreened due to a lack of clear guidelines for regular B12 screening. We therefore investigated the determinants of B12 deficiency in community-dwelling patients with T2DM, with the aim of profiling patients most in need of B12-deficiency screening. METHODS: B12 deficiency was evaluated using a retrospective cross-sectional cohort of 592 primary-care patients with T2DM, recruited from 2008 to 2011 from a Polyclinic in Singapore. RESULTS: B12 deficiency (serum B12 < 150 pmol/L) was present in 164 (27.7%) patients and was associated with a higher "metformin daily dose" (OR = 2.79; 95% CI, 2.22-3.48, P < 0.001); "age ≥ 80 years" (OR = 2.86; 95% CI, 1.31-6.25, P = 0.008); "vegetarianism" (OR = 21.61; 95% CI, 4.47-104.44, P < 0.001); and "folate deficiency" (OR = 2.04; 95% CI, 1.27-3.28, P = 0.003). Conversely, "Prescribed B12 supplementation" was associated with a lower odds of B12 deficiency (OR = 0.37; 95% CI: 0.22-0.61, P < 0.001). The area under the receiver operating characteristic curve was 0.803 (95% CI: 0.765-0.842). "Metformin daily dose" correlated interchangeably with "Metformin 1-year cumulative dose" (r = 0.960; P < 0.01), and also associated linearly with "duration of diabetes" (B = 0.113, P < 0.0001). Independent of the duration of T2DM, 29.3% of the B12-deficient patients needed > 1 screening test before the detection of B12 deficiency. CONCLUSIONS: Primary-care screening for B12 deficiency should be part of the annual laboratory review of patients with T2DM regardless of the duration of T2DM -especially when they are prescribed ≥ 1.5 g/day of metformin; ≥ 80 years old; vegetarian; and not prescribed B12 supplementation. Concurrent evaluation for associated folate (vitamin B9) deficiency is essential when addressing T2DM-associated B12 deficiencies. Current "Metformin daily dose" is an accurate proxy of both cumulative metformin exposure and duration of T2DM.

Functional vitamin B12 deficiency: Improving methylmalonic acid reference intervals in urine.

BACKGROUND-AIM: Most laboratory requests focus on the detection of possible vitamin B12 deficiency. In this context, methylmalonic acid (MMA) is reported as the best biomarker. The aim of our study was to establish the biological reference interval for MMA in urine, and assess the influence of age, sex, and vitamin B12 status on MMA concentrations. METHODS: This is a prospective observational study considering individuals with normal results for blood count and liver and kidney function. Individuals who presented supplementation, any pathology or treatment that could cause cobalamin metabolism disorders, and pregnant women were excluded. Likewise, individuals whose vitamin B12 result presented antibody-mediated interference were excluded. Individuals were grouped by age-group and sex. Reference intervals were determined by non-parametric calculation (percentiles 1-99). RESULTS: It was established a single reference interval [0.52 (CI90%: 0.50-0.54) - 5.75 (CI90%: 5.57-6.17) mmolMMA/mol creatinine], with 100 % of individuals with MMA above the upper limit of reference presenting a total vitamin B12 concentration ≤ 238 pmol/L. CONCLUSION: The establishment of optimal reference intervals for methylmalonic acid excretion in urine is crucial in individuals with a suspicion of functional vitamin B12 deficiency. However, the possibility of establishing a cut-off value for total vitamin B12 suggesting subclinical deficiency remains a challenge for this magnitude.

Vitamin B12 deficiency presenting with a pancytopenia in pregnancy.

Vitamin B12 deficiency is a significant public health problem globally. Although it is a well-known cause of macrocytic anaemia and in advanced cases, pancytopenia, there remains a relative paucity of cases reported in pregnancy. It is associated with an increased risk of pregnancy complications and adverse birth outcomes such as neural tube defects, preterm birth, low birth weight, neurological sequelae and intrauterine death. It has a predilection for individuals aged >60 years. It has been implicated in a spectrum of neuropsychiatric disorders and it may also exert indirect cardiovascular effects. Severe vitamin B12 deficiency may present with haematological abnormalities that mimic thrombotic microangiopathy such as HELLP syndrome (haemolysis, elevated liver enzymes and low platelets) or it may present as pseudothrombotic microangiopathy (Moschcowitz syndrome) characterised by anaemia, thrombocytopenia and schistocytosis. It can also closely mimic thrombotic thrombocytopenia purpura, hence posing a diagnostic challenge to the unwary physician. Serological measurement of vitamin B12 levels confirms the diagnosis. Oral supplementation with vitamin B12 remains a safe and effective treatment. The authors describe the case of a multiparous woman in her late 20s presenting with a plethora of non-specific symptoms at 29+5 weeks' gestation. Her haemoglobin was 45 g/L, platelets 32×109/L, vitamin B12 <150 ng/L and serum folate <2 µg/L. She was not a vegetarian, but her diet lacked nutrition. Following parenteral B12 supplementation, her haematological parameters improved. The pregnancy was carried to term. Due to the plethora of non-specific symptoms, the diagnosis can be challenging to establish. Adverse maternal or fetal outcomes may occur. Folic acid supplementation may mask an occult vitamin B12 deficiency and further exacerbate or initiate neurological disease.

Clinical Course of Vitamin B12 Deficiency and Associated Risk Factors in Patients After Total Gastrectomy for Gastric Cancer.

BACKGROUND/AIM: Patients are at-risk for vitamin B12 deficiency after total gastrectomy due to a lack of intrinsic factors. The aim of the study was to clarify the clinical course and risk factors for vitamin B12 deficiency after total gastrectomy for gastric cancer patients. PATIENTS AND METHODS: Patients who underwent curative resection for gastric cancer were selected from the medical records of the Yokohama City University from 2000 to 2020. A logistic regression analysis was performed to identify risk factors for vitamin B12 deficiency. RESULTS: We evaluated 47 patients. The median serum vitamin B12 levels before surgery were 359 pg/ml, while those at 3, 6, 9, and 12 months after surgery these were 255 pg/ml, 197.5 pg/ml, 195 pg/ml, and 206 pg/ml, respectively. Univariate analyses to identify factors associated with vitamin B12 deficiency at 6 months after surgery showed that the occurrence of postoperative complications was a significant risk factor (OR=6.347, 95%CI=1.607-25.774, p=0.009), while adjuvant chemotherapy was a marginally significantly risk factor (OR=3.562, 95%CI=0.877-14.477, p=0.076). CONCLUSION: Almost half of the patients were diagnosed with vitamin B12 deficiency at 6 months after total gastrectomy for gastric cancer. In addition, the occurrence of postoperative complications and adjuvant chemotherapy were risk factors for vitamin B12 deficiency at 6 months after surgery.

Acquired Vitamin B12 Deficiency in Newborns: Positive Impact on Newborn Health through Early Detection.

The early diagnosis of and intervention in vitamin B12 deficiency in exclusively breastfed infants by mothers with low vitamin B12 is crucial in preventing possible irreversible neurologic damage, megaloblastic anemia, and failure to thrive. We assess the usefulness of the early detection of asymptomatic B12 deficiency related to acquired conditions and highlight the importance of monitoring serum vitamin B12 levels during pregnancy. We describe demographic, clinical, dietary, and biochemical data, including the evolution of a vitamin B12 deficiency's functional biomarkers. We enrolled 12 newborns (5 males) with an age range of 1-2 months old that were exclusively breastfed and asymptomatic. These cases were referred to our metabolic unit due to alterations in expanded newborn screening: high levels of methylmalonic acid and/or total homocysteine (tHcy). All mothers were under a vegetarian diet except three who had abnormal B12 absorption, and all presented low or borderline serum B12 level and high plasma levels of tHcy. Supplementation with oral vitB12 re-established the metabolic homeostasis of the mothers. In infants, therapy with an intramuscular injection of 1.0 mg hydroxocobalamin led to the rapid normalization of the metabolic pattern, and a healthy outcome was observed. Acquired B12 deficiency should be ruled out before proceeding in a differential diagnosis of cobalamin metabolism deficits, methylmalonic acidemia, and homocystinuria.

Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Fylkesforskjeller i utredning og behandling av vitamin B12-mangel.

BACKGROUND: Severe vitamin B12 (cobalamin) deficiency is rare, but international reports show that up to 26 % of the general population may have subclinical vitamin B12 deficiency. The prevalence of vitamin B12 deficiency has not been investigated in Norway. Since 2017, treatment with vitamin B12 tablets has represented an alternative to traditional treatment with intramuscular injections in Norway. When we studied the transition from injection to tablet treatment, we discovered an unexpected difference in the counties' use of vitamin B12 supplements, which we wished to investigate in more detail. MATERIAL AND METHOD: Data on the dispensing of vitamin B12 supplements from pharmacies in 2020, broken down by the patients' county of residence, were retrieved from the Norwegian Prescription Database. The Norwegian Health Economics Administration (Helfo) provided figures on the number of reimbursed vitamin B12-related laboratory tests in 2020, classified by patients' municipality of residence. RESULTS: In 2020, the sale of vitamin B12 supplements on prescription in Norway amounted to 12 defined daily doses (DDD) per inhabitant and varied from 7 to 15 between the counties. The number of laboratory analyses that were performed varied by county from 26 to 46 per 100 inhabitants for total vitamin B12, and from 21 to 37 for folate. The number of analyses varied correspondingly from 1 to 12 per 100 inhabitants for homocysteine, from 1 to 13 for methylmalonic acid and from 0.01 to 8.13 for active vitamin B12. INTERPRETATION: Our study showed large intercounty differences in the consumption of vitamin B12 supplements. These differences may have a number of explanations. Variations in the number of vitamin B12-related laboratory analyses requisitioned may indicate that doctors' assessment and diagnosis of vitamin B12 deficiency could be a contributory factor.

Differentiation of Reversible Hemichorea Due to Vitamin B12 Deficiency From Huntington Disease Via FDG PET.

ABSTRACT: Vitamin B12 deficiency may present with diverse symptoms, complicating the differential diagnosis. Extrapyramidal movement disorders, for instance, are a rare manifestation of vitamin B12 deficiency. MRI of the brain frequently remains without conclusive findings. However, 18 F-FDG PET/CT may reveal characteristic changes in the metabolism of the basal ganglia and thus contribute to an accurate diagnosis. We demonstrate the case of a woman with left-sided hemichoreatic movements due to vitamin B12 deficiency showing a contralateral putaminal hypermetabolism, which normalized after vitamin B12 supplementation, ruling out other deviating causes, particularly Huntington disease.

Vitamin B12 Deficiency in Patients with Diabetes on Metformin: Arab Countries.

BACKGROUND: Diabetes is a global pandemic, especially in Arab countries. AIM: The goal of this study was to review the published studies that were conducted to determine the relationship between metformin treatment for type 2 diabetes mellitus (T2DM) and vitamin B12 deficiency and to identify possible complications in this relationship. METHODS: I searched for all relevant studies published in English before 2020 on the PubMed and Web of Knowledge databases using the following terms: "metformin", "vitamin B12", "neuropathy", "diabetes mellitus", and Middle Eastern countries. RESULTS: Eleven studies were included in this review which indicated an association between taking metformin and B12 deficiency in patients with T2DM in Arab countries. This B12 deficiency was found to be negatively associated with the dose and duration of metformin therapy. The physician's knowledge of current ADA recommendations regarding supplementation with and screening of the B12 level for T2DM patients on metformin was also found to have an effect. CONCLUSION: Metformin therapy is associated with B12 deficiency among people with T2DM in Arabic countries. Thus, diabetes must be managed in compliance with current guidelines and recommendations, and B12 levels must be routinely monitored, particularly in those who have been long-term takers of metformin, to ensure the suitable management of diabetes and its complications.

Very long-term outcomes in 23 patients with cblA type methylmalonic acidemia.

OBJECTIVES: To present the very long-term follow up of patients with cobalamin A (cblA) deficiency. METHODS: A retrospective case series of adult (>16 years) patients with molecular or enzymatic diagnosis of cblA deficiency. RESULTS: We included 23 patients (mean age: 27 ± 7.6 years; mean follow-up: 24.9 ± 7.6 years). Disease onset was mostly pediatric (78% < 1 year, median = 4 months) with acute neurologic deterioration (65%). Eight patients presented with chronic symptoms, and one had an adult-onset mild cblA deficiency. Most of the patients (61%) were initially classified as vitamin B12-unresponsive methylmalonic aciduria (MMA); in vitro B12 responsiveness was subsequently found in all the tested patients (n = 13). Initial management consisted of protein restriction (57%), B12 (17%), or both (26%). The main long-term problems were intellectual disability (39%) and renal failure (30%). However, 56.5% of the patients were living independently. Intellectual disability was equally distributed among the initial treatment groups, while renal failure (moderate and beginning at the age of 38 years) was present in only one out of seven patients initially treated with B12. CONCLUSIONS: We provide a detailed picture of the long-term outcome of a series of adult cblA patients, mostly diagnosed before the enzymatic and molecular era. We confirm that about 35% of the patients do not present acutely, underlining the importance of measuring MMA in any case of unexplained chronic renal failure, intellectual disability, or growth delay. In addition, we describe a patient with a milder adult-onset form. Early B12 supplementation seems to protect from severe renal insufficiency.