Low utility of serum folic acid blood tests in healthy children and adolescents, a nationwide cohort.

This study aimed to evaluate the utility of serum folic acid testing in children and adolescents in a developed country without mandatory folic acid food fortification and to identify patients at risk for folic acid deficiency. In this cross-sectional study, records from primary care and hospitals were reviewed for patients aged 0-18 years who underwent serum folic acid testing. Data were retrieved from the Leumit-Health-Services database over a ten-year period (January 2008 to December 2018). Clinical and laboratory data were compared between patients with folic acid deficiency to those with normal levels. Among 20,411 pediatric patients tested, 884 (4.3%) had folic acid deficiency, of whom only 26.3% had anemia. Only two patients (0.2%) had megaloblastic anemia. Multivariate analysis showed that male gender (odds ratio(OR)1.6, 95% CI 1.22-2.12), older age (OR 1.32, 95% CI 1.26-1.39), higher BMI percentile (OR 1.01, 95% CI 1-1.01), antipsychotic treatment (OR 3.23, 95% CI 1.52-6.84), celiac (OR 2.97, 95% CI 1.66-5.34), and Attention-Deficit-and-Hyperactivity-Disease (ADHD) treated with psychostimulants (OR 2.21, 95% CI 1.56-3.12) were associated with folic acid deficiency(all p < 0.01). Lower hemoglobin levels were independently associated with increased OR of folic acid deficiency (OR 0.77, 95% CI 0.66-0.90, p = 0.001), but anemia as a diagnosis was not. CONCLUSION: Pediatric folic acid deficiency rates were low in this nationwide cohort and not linked to megaloblastic anemia, likely due to concomitant iron deficiency anemia. Although retrospective, this might suggest low utility for routine serum folic acid testing in healthy children in developed countries, except in cases of celiac disease or specific medication use such psychostimulants or antipsychotics. WHAT IS KNOWN: • Folic acid deficiency is common among children in developing countries, causing megaloblastic anemia, growth delays, and cognitive impairments. In developed countries, the prevalence is considered low. WHAT IS NEW: • Of 20,411 pediatric patients tested for serum folate, in a developed country, only 4.3% had folate deficiency. • Risk factors for deficiency included celiac, antipsychotics, and psychostimulant treatment for ADHD. • Routine folate testing in developed countries may have limited utility; Targeted screening is recommended.

Atezolizumab-induced hemolytic anemia - A case report.

INTRODUCTION: Atezolizumab is currently the only immunotherapy used in conjunction with nab-paclitaxel for locally advanced or triple negative breast cancer. Limited data is available regarding hemolytic anemia as a side effect of atezolizumab. CASE REPORT: We describe a 59-year-old female with a history of triple negative breast cancer with bone metastases presenting for follow up on Cycle 1, Day 15 of atezolizumab and nab-paclitaxel (100 mg/m2). Patient's complete blood count (CBC) showed macrocytic anemia, with further workup significant for autoimmune hemolytic anemia (AIHA) attributed to atezolizumab.Management and outcome: Patient was started on a high dose prednisone taper starting at 80 mg daily for 16 days, folic acid 1 mg three times daily, iron sucrose, and darbepoetin alfa. Patient's counts recovered, and she was able to start Cycle 2 and continued through Cycle 10 without any additional pre-medications. DISCUSSION: Hemolytic anemia induced by atezolizumab is a rare side effect that was successfully treated in this patient with a prednisone taper.

Macrocytic anemia in Lesch-Nyhan disease and its variants.

PURPOSE: Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was  to describe macrocytic erythrocytes as another common aspect of the phenotype. METHODS: The results of 257 complete blood counts from 65 patients over a 23-year period were collected from 2 reference centers where many patients are seen regularly. RESULTS: Macrocytic erythrocytes occurred in 81-92% of subjects with Lesch-Nyhan disease or its neurological variants. After excluding cases with iron deficiency because it might pseudonormalize erythrocyte volumes, macrocytosis occurred in 97% of subjects. Macrocytic erythrocytes were sometimes accompanied by mild anemia, and rarely by severe anemia. CONCLUSION: These results establish macrocytic erythrocytes as a very common aspect of the clinical phenotype of Lesch-Nyhan disease and its neurological variants. Macrocytosis is so characteristic that its absence should prompt suspicion of a secondary process, such as iron deficiency. Because macrocytosis is uncommon in unaffected children, it can also be used as a clue for early diagnosis in children with neurodevelopmental delay. Better recognition of this characteristic feature of the disorder will also help to prevent unnecessary diagnostic testing and unnecessary attempts to treat it with folate or B12 supplements.

ZRSR2 mutation in a child with refractory macrocytic anemia and Down Syndrome.

Here we report a case of refractory macrocytic anemia with a spliceosomal point mutation involving the ZRSR2 gene in a child with Down syndrome (DS). Such mutations have been shown to cause refractory macrocytic anemia and myelodysplastic syndrome (MDS) in elderly individuals. We report the hematological indices of a child with DS and a ZRSR2 spliceosomal mutation. DS is known to produce macrocytic anemia but does not lead to transfusion dependence. In this case, the ZRSR2 mutation was the likely implicating factor for severe transfusion-dependent anemia in a child with DS. The clinical implication of a ZRSR2 mutation in a child with DS has not been previously described and warrants close surveillance to detect potential insidious transformation to MDS.

Imerslund-Gräsbeck Syndrome in an Infant with a Novel Intronic Variant in the AMN Gene: A Case Report.

Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder clinically characterized by megaloblastic anemia, benign mild proteinuria, and other nonspecific symptoms. Several pathogenetic variants in the amnionless (AMN) or cubilin (CUBN) genes have been described in IGS. We describe a case of IGS with urinary tract infection and mild but persistent proteinuria at onset in an 11-month-old female child. With the appearance of macrocytic anemia, aphthous stomatitis, and neurological signs, IGS was clinically suspected, and vitamin B12 parenteral therapy was started. Sequence analysis showed the presence of a novel intronic variant c.513+5G>A of AMN, never before described in the literature, that was in compound heterozygosity with the known pathogenetic variant c.1006+34_1007-31del. Analysis extension to the parents revealed the presence of variant c.1006+34_1007-31 in the father and c.513+5G>A in the mother. In the present case with IGS, the novel intronic variant of AMN was identified in "trans" with a known pathogenic variant (c.1006-31 del) and the new variant was interpreted to be pathogenetic since it was not found in the public database of polymorphisms and because it was predicted to alter a donor splicing site. Our case underlines the relevance in detecting certain subtle symptoms, such as mild but persistent proteinuria associated with megaloblastic anemia, to reach a correct diagnosis of a rare but treatable disorder.

Abnormal folate metabolism causes age-, sex- and parent-of-origin-specific haematological defects in mice.

KEY POINTS: Folate (folic acid) deficiency and mutations in folate-related genes in humans result in megaloblastic anaemia. Folate metabolism, which requires the enzyme methionine synthase reductase (MTRR), is necessary for DNA synthesis and the transmission of one-carbon methyl groups for cellular methylation. In this study, we show that the hypomorphic Mtrrgt/gt mutation in mice results in late-onset and sex-specific blood defects, including macrocytic anaemia, extramedullary haematopoiesis and lymphopenia. Notably, when either parent carries an Mtrrgt allele, blood phenotypes result in their genetically wildtype adult daughters, the effects of which are parent specific. Our data establish a new model for studying the mechanism of folate metabolism in macrocytic anaemia aetiology and suggest that assessing parental folate status might be important when diagnosing adult patients with unexplained anaemia. ABSTRACT: The importance of the vitamin folate (also known as folic acid) in erythrocyte formation, maturation and/or longevity is apparent since folate deficiency in humans causes megaloblastic anaemia. Megaloblastic anaemia is a type of macrocytic anaemia whereby erythrocytes are enlarged and fewer in number. Folate metabolism is required for thymidine synthesis and one-carbon metabolism, though its specific role in erythropoiesis is not well understood. Methionine synthase reductase (MTRR) is a key enzyme necessary for the progression of folate metabolism since knocking down the Mtrr gene in mice results in hyperhomocysteinaemia and global DNA hypomethylation. We demonstrate here that abnormal folate metabolism in mice caused by Mtrrgt/gt homozygosity leads to haematopoietic phenotypes that are sex and age dependent. Specifically, Mtrrgt/gt female mice displayed macrocytic anaemia, which might be due to defective erythroid differentiation at the exclusion of haemolysis. This was associated with increased renal Epo mRNA expression, hypercellular bone marrow, and splenic extramedullary haematopoiesis. In contrast, the male response differed since Mtrrgt/gt male mice were not anaemic but did display erythrocytic macrocytosis and lymphopenia. Regardless of sex, these phenotypes were late onset. Remarkably, we also show that when either parent carries an Mtrrgt allele, a haematological defect results in their adult wildtype daughters. However, the specific phenotype was dependent upon the sex of the parent. For instance, wildtype daughters of Mtrr+/gt females displayed normocytic anaemia. In contrast, wildtype daughters of Mtrr+/gt males exhibited erythrocytic microcytosis not associated with anaemia. Therefore, abnormal folate metabolism affects adult haematopoiesis in an age-, sex- and parent-specific manner.

Macrocytic anemia is associated with the severity of liver impairment in patients with hepatitis B virus-related decompensated cirrhosis: a retrospective cross-sectional study.

BACKGROUND: Macrocytic anemia is common in liver disease. However, its role in hepatitis B virus (HBV)-related decompensated cirrhosis remains unknown. The aim of the present study was to determine the association between macrocytic anemia and the severity of liver impairment in patients with HBV-related decompensated cirrhosis according to the Model for End Stage Liver Disease (MELD) score. METHODS: A total of 463 participants who fulfilled our criteria were enrolled in this cross-sectional study. Patients were classified into three groups according to anemia types, diagnosed based on their mean corpuscular volume level. Multivariate linear regression analyses were used to determine the association between macrocytic anemia and the MELD score for patients with HBV-related decompensated cirrhosis. RESULTS: Patients with macrocytic anemia had evidently higher MELD scores (10.8 ± 6.6) than those with normocytic anemia (8.0 ± 5.5) or microcytic anemia (6.3 ± 5.1). The association remained robust after adjusting for age, gender, smoking, drinking, and total cholesterol (ß = 1.94, CI: 0.81-3.07, P < 0.001). CONCLUSIONS: Macrocytic anemia was found to be associated with the severity of liver impairment and might be a predictor for short-term mortality in patients with HBV-related decompensated cirrhosis.

Correlation of Red Blood Cell Acetylcholinesterase Enzyme Activity with Various RBC Indices.

Cholinesterases belongs to class hydrolases. There are two types acetylcholinesterase and butyryl cholinesterase. Acetylcholinesterase present in nerve endings and also in the RBC membrane. It helps to maintain the shape and size of RBCs. Any change in shape and size of RBCs may affect the activity of Acetylcholinesterase. Thus this study aimed to estimate RBCs Acetylcholinesterase enzyme activity in various types of anemias and correlate the RBCs Acetylcholinesterase enzyme activity with various hematological indices such as Erythrocyte Sedimentation Rate (ESR), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume (MCV), Red cell Distribution Width (RDW) etc. After obtaining ethical approval from Institutional ethics committee total of 100 samples were collected from Clinical Biochemistry laboratory, Kasturba Medical College, Manipal, Manipal University. 25 were having normal RBC indices, 12 with hemolytic anemia, 26 with microcytic anemia and 26 with macrocytic anemia based on peripheral smear report and RBC indices. Acetylcholinesterase were measured using Ellman's method. RBC acetylcholinesterase activity was significantly increased in microcytic anemia (58.13 ± 5.4) and macrocytic anemia (76.87 ± 6.7) than normal group (37.62 ± 2.71). Also increased RBC acetylcholinesterase was seen in hemolytic anemia (48.11 ± 5.18) but the increase is not statistically significant. RBC acetylcholinesterase correlated negatively with hemoglobin (r = -0.356, p = 0.001) and positively with RDW (r = 0.31, p = 0.003). To conclude RBC acetylcholinesterase activity can be used as one of the potential marker for various types of anemia.

A descriptive study of clinico-hematological profile of megaloblastic anemia in a tertiary care hospital.

BACKGROUND: Megaloblastic Anemia (MA) is a relatively common disease, yet the data on prevalence of MA remains scarce. This study was conducted to study the prevalence and clinico-hematological profile of MA. METHODS: This was a cross-sectional study done on 1150 adult anemic patients. All patients diagnosed to have MA were studied for clinico-hematological and etiological profile. Nerve conduction studies (NCS) were done in all. RESULTS: MA was present in 3.6% cases of anemia. Severe anemia was seen in 9.7% of anemic patients and 75% of MA cases (p < 0.05). Forty five percent of MA patients presented with pancytopenia. Vitamin B12 and folic acid deficiency were documented in 40% and 25% cases respectively while combined deficiency was noted in 35% of all MA cases. There was no co-relation between severity of anemia and deficiency of either of the vitamins (Fischer exact test: 0.530). Among MA patients, 35% were vegetarians while 65% consumed mixed diet. There was no association between vegetarian diet and Vit B12 deficiency (p = 0.3137). An additional etiology was more commonly found in patients on mixed diet [92%; 24/26] as compared to those on vegetarian diet [50%; 7/14] (p = 0.04). NCS was abnormal in 14 patients (35%). Overt clinical neuropathy was present in 12 cases of MA, while subclinical neuropathy was seen in 2 cases. CONCLUSION: MA is one of common causes of pancytopenia and severe anemia. Diet plays an important role in causation of MA in vegetarians. An alternative etiology is however, more likely to be found in patients on mixed diet. While overt neurological abnormalities are common in MA, subclinical neuropathy is uncommon.

Recovery from anemia and leukocytopenia after abstinence in Japanese alcoholic men and their genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2.

BACKGROUND: The combination of the fast-metabolizing alcohol dehydrogenase-1B (ADH1B*2 allele) and inactive heterozygous aldehyde dehydrogenase-2 (ALDH2*1/*2) increases susceptibility to macrocytic anemia and leukocytopenia in alcoholics due to severe acetaldehydemia. More than half of Japanese drinkers with esophageal cancer have this genotype combination. METHODS: To assess the recovery of hematologic abnormalities after drinking cessation, changes in blood erythrocyte indices and leukocyte count during 8-week hospital stay were evaluated in 925 Japanese alcoholic men. We used four categories in ascending order for high blood acetaldehyde exposure from drinking: A, ADH1B*1/*1 plus ALDH2*1/*1; B, ADH1B*2 plus ALDH2*1/*1; C, ADH1B*1/*1 plus ALDH2*1/*2; and D, ADH1B*2 plus ALDH2*1/*2. RESULTS: Mean values of hemoglobin and hematocrit were the lowest, and those of mean corpuscular volume (MCV) were markedly the highest in the D group on admission, and returning toward normal after abstinence, but the inter-group differences remained significant throughout the 8 weeks. The mean leukocyte count was the lowest in the D group on admission, but increased during 4-week abstinence when the inter-group differences were no longer significant. Frequencies of MCV ≥110 fl (50.5%), hemoglobin levels <11.5 g/dL (32.7%), hemoglobin levels <10.0 g/dL (9.9%) and leukocytopenia <4000/µL (22.8%) were the highest in the D group on the admission day and decreased at the 4-week abstinence (28.7%, 18.8%, 4.0% and 7.9%, respectively). The inter-group differences in frequencies of the severe anemia and leukocytopenia disappeared after 4-week abstinence. CONCLUSIONS: Drinking cessation before surgery and/or chemoradiation treatment for esophageal cancer may be effective for recovery from anemia and leukocytopenia in drinkers belonging to the D group.

Hematinic deficiencies and anemia statuses in oral mucosal disease patients with folic acid deficiency.

BACKGROUND/PURPOSE: Folic acid deficiency (FAD) may result in macrocytic anemia. This study assessed the hematinic deficiencies and anemia statuses in oral mucosal disease patients with FAD (defined as folic acid ≤ 6 ng/mL). METHODS: The blood hemoglobin (Hb), iron, vitamin B12, and folic acid concentrations, serum gastric parietal cell antibody level, and mean corpuscular volume (MCV) in 198 oral mucosal disease patients with FAD were measured. Based on World Health Organization (WHO) criteria, anemia or Hb deficiency was defined as having an Hb concentration of <13 g/dL for men and <12 g/dL for women. In this study, macrocytic anemia due to FAD was defined as having an MCV ≥100 fL and folic acid ≤6 ng/mL; pernicious anemia as having MCV ≥100 fL, vitamin B12 < 200 pg/mL, and serum gastric parietal cell antibody positivity; iron deficiency anemia as having MCV <80 fL and iron <60 µg/dL; and thalassemia trait as having MCV <74 fL, red blood cell (RBC) count > 5.0 × 10(12)/L, and Mentzer index (MCV/RBC) < 13. RESULTS: We found that by WHO definitions, 73 (36.9%), 41 (20.7%), and 10 (5.1%) of our 198 FAD patients had concomitant Hb, iron, and vitamin B12 deficiencies, respectively. Of 73 anemic FAD patients, three had macrocytic anemia due to FAD, one had pernicious anemia, 14 had iron deficiency anemia, eight had thalassemia trait, and the resting 47 had normocytic anemia. CONCLUSION: In addition to macrocytic anemia (2.0%), FAD patients may have concomitant normocytic (23.7%) or microcytic (11.1%) anemia.

Comparison of Patients Receiving Long-Term Metformin Therapy and Vitamin B12 Monitoring.

Background: Metformin may cause vitamin B12 deficiency that can present with symptoms of peripheral neuropathy. Lack of vitamin B12 serum concentration monitoring could result in vitamin B12 deficiency progression, worsening of symptoms, and unnecessary medication. Objectives: The purpose of this study was to (a) compare the influence of the rate of symptoms consistent with vitamin B12 deficiency on obtaining vitamin B12 serum concentrations in patients using metformin; (b) assess if vitamin B12 serum concentrations were ordered as a routine monitoring parameter. Methods: This retrospective case-control study evaluated patients receiving metformin. Patients in the case group had documented symptoms or diagnosis of peripheral neuropathy or macrocytic anemia, while those in the control group did not. The primary outcome was frequency of vitamin B12 serum concentration assessment. The secondary outcomes included frequency of vitamin B12 serum concentration assessment for patients presenting with symptoms or diagnosis of peripheral neuropathy or macrocytic anemia. Results: Analysis included 355 patients (116 cases, 239 controls). The cases were 5 times more likely to have a serum vitamin B12 serum concentrations drawn versus controls (odds ratio [OR] = 5.83, 95% confidence interval [CI] = 3.47-9.77, P < .001). Patients with a diagnosis of peripheral neuropathy or macrocytic anemia were 4 times more likely to have a serum vitamin B12 concentration drawn than those who did not (peripheral neuropathy: OR = 4.92, 95% CI = 2.95-8.21, P < .001; macrocytic anemia: OR = 5.41, 95% CI = 1.30-20.97, P = .007). Conclusions: Cases were more likely to have vitamin B12 serum concentrations assessed than patients without symptoms. The majority of patients taking metformin did not have routine vitamin B12 serum concentration assessments for medication adverse event monitoring.

Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28.

Patients with physical findings suggestive of Treacher Collins syndrome (TCS) or mandibulofacial dysostosis (MFD) and macrocytic anemia diagnostic of Diamond-Blackfan anemia (DBA) have been reported. Disease-causing genes have been identified for TCS and other MFDs. Mutations in several ribosomal protein genes and the transcription factor GATA1 result in DBA. However, no disease-causing mutation had been identified in the reported patients with the combination of TCS/MFD and DBA phenotype, and we hypothesized that pathogenic mutations in a single gene could be identified using whole exome analysis. We studied probands from six unrelated families. Combining exome analysis and Sanger sequencing, we identified likely pathogenic mutations in 5/6 families. Two mutations in unrelated families were seen in RPS26, the known DBA10 gene. One variant was predicted to affect mRNA splicing, and the other to lead to protein truncation. In another family a likely pathogenic X-linked mutation affecting a highly conserved residue was found in TSR2, which encodes a direct binding partner of RPS26. De novo mutations affecting the RPS28 start codon were found in two unrelated probands, identifying RPS28 as a novel disease gene. We conclude that the phenotype combining features of TCS with DBA is genetically heterogeneous. Each of the pathogenic variants identified is predicted to impede ribosome biogenesis, which in turn could result in altered cell growth and proliferation, causing abnormal embryologic development, defective erythropoiesis and reduced growth. The phenotype combining TCS/MFD and DBA is highly variable, overlaps with DBA and lies within the phenotypic spectrum of ribosomopathies. © 2014 Wiley Periodicals, Inc.

Prevalence of pernicious anemia in patients with macrocytic anemia and low serum B12.

OBJECTIVE: The current research evaluated the prevalence of pernicious anemia (PA) in patients with macrocytic anemia (high MCV) and low serum B12 in Riyadh. METHODS: Blood testing was done in 77 patients (males: 45.5%, females: 54.5%) with macrocytic anemia; 84 patients; (males: 23.8%, females: 76.2%) with low serum B12 and 30 healthy subjects. Complete blood count, differential count, folic acid, vitamin B12, intrinsic factor, gastric parietal cell antibodies and holotranscobalamin II were assessed. RESULTS: A total of five subjects from 161 patients had PA; three of these patients had macrocyticanemia (3.90%) and two patients had low serum B12 (2.38%). Significant differences (p<0.05) in some hematological, immunological, biochemical parameters were found in subjects with macrocytic anemia and low serum B12 compared to controls. CONCLUSIONS: Pernicious anemia in patients with macrocytic anemia and low serum B12 was for the selected sample size can be assumed to be uncommon in Riyadh, Saudi Arabia.

Frequency and Types of Anemia in Primary Hypothyroidism Patients: A Prospective Observational Study.

Background Primary hypothyroidism is a common endocrine disorder resulting from inadequate production of thyroid hormones. Anemia is a common condition that can occur in hypothyroidism. Anemia may occur due to nutrient deficiency, such as iron or vitamin B12 deficiency due to chronic disease in hypothyroidism. Therefore, it is important to evaluate the cause of anemia in hypothyroidism.  Objective The aim of this study was to determine the frequency of anemia and its types in patients with primary hypothyroidism. Methods This was a prospective cross-sectional observational study conducted at the Department of Medicine, Jinnah Postgraduate Medical Center, Karachi, Pakistan, using non-probability consecutive sampling. A total of 176 adults aged 18-65 years of either gender, newly diagnosed with primary hypothyroidism, or with any of its symptoms were included in the study. Patients already on anti-thyroid medication and with post-thyroidectomy hypothyroidism were excluded from the study. The duration of the study was 1.5 years, from January 2020 to July 2021. After ethical approval, written informed consent was obtained from each patient. Demographical data along with results of complete blood picture, including Hb and MCV for diagnosing anemia and its types were recorded on a pre-designed proforma. The chi-square test was applied keeping p < 0.05 as statistically significant. Results The mean age of the patients was 42.19 ± 8.43 years, with 59.66% (n = 105) females and 40.34% (n = 71) males. A total of 67% (n =118) patients were found to be anemic. Of these, 38.64% (n = 68) patients had normocytic anemia, 19.32% (n = 34) microcytic anemia, and 9.25% (n = 16) patients had macrocytic anemia; 56.34% (n = 40) males and 74.29% (n = 78) females were reported to be anemic (p = 0.01). Conclusion In our study, the frequency of anemia in patients with hypothyroidism was high, with normocytic anemia being the most common type. It is important to know the type of anemia in hypothyroidism, as normocytic anemia is due to the chronic disease process (anemia of chronic disease) and may not respond to nutrient supplementation. Conversely, microcytic anemia is commonly due to iron deficiency and macrocytic anemia is due to vitamin B12 deficiency and therefore, they require replacement therapy. In any case, it is important to identify and treat the underlying cause of anemia.

Acute Mental Disorder Caused by Vitamin B12 Deficiency Eight Years After Total Gastrectomy.

Vitamin B12 deficiency can cause a variety of diseases. The most common disease is macrocytic anemia, but it has also been found to be a cause of psychiatric disorders. The causes of deficiency are varied, and diagnosis is often difficult. Here, we report a patient who developed mental disorders due to vitamin B12 deficiency after total gastrectomy. A 37-year-old female, eight years after total gastrectomy, was withdrawn at her workplace, talking and acting abnormally. The family had seen unusual behavior for three days. The patient had no particular history of mental illness. The possibility of herpes encephalitis was suspected, and the patient was referred to our hospital, but there were no specific findings in the head on imaging examination. Blood tests showed no macrocytic anemia. Spinal fluid cytology and electroencephalography showed no specific findings, and herpes DNA was negative. Metabolic factors such as vitamin deficiency were considered, and intravenous vitamin replacement therapy was initiated. The psychiatric symptoms improved rapidly after vitamin B12 supplementation was started. On the fifth day of her hospitalization, it was discovered that her vitamin B12 level at the time of admission was extremely low. Typically, vitamin B12 deficiency is associated with macrocytic anemia, but in this patient, serum iron was also decreased, indicating a mixed anemia, making the diagnosis difficult. The patient had undergone a total gastrectomy for gastric cancer eight years ago, and the psychiatric symptoms were thought to be due to impaired vitamin B12 absorption caused by intrinsic factor deficiency. Since then, oral replacement therapy and intramuscular injection have been continued without recurrence of symptoms. Disturbances of consciousness may have many causes, but when there is a history of gastrectomy, we should also consider vitamin B12 deficiency when examining patients.

A Rare Case of Gastric Neuroendocrine Tumor in a Patient With Vitamin B12 Deficiency.

Vitamin B12 deficiency can result from gastric neuroendocrine tumors (GNETs), which are uncommon neoplasms frequently linked to hypergastrinemia and chronic atrophic gastritis. Here, we report the case of a 48-year-old vegetarian male from South India who presented with jaundice, fatigue, and gastrointestinal discomfort. He was diagnosed with macrocytic anemia, mild hepatomegaly, and significant vitamin B12 deficiency. An incidental upper gastrointestinal endoscopy revealed multiple gastric nodules, later confirmed as a well-differentiated GNET. The patient also had a high hepatitis B viral load. He was treated with vitamin B12 supplementation and underwent resection of the tumor followed by antiviral therapy for hepatitis B. Postoperative recovery was uneventful with improvements in anemia and liver function. This case emphasizes the importance of a multidisciplinary approach and thorough evaluation when addressing patients with vitamin B12 insufficiency, hepatitis B, and GNET.

Methylcobalamin Deficiency Presenting as Thalamic Syndrome in the Elderly: Association or Chance?

Vitamin deficiency is common in the geriatric population and is responsible for majorly imbalanced hematological, neurological, and neuropsychiatric functioning. Methylcobalamin deficiency or vitamin B12 deficiency can be underestimated in some cases and be misdiagnosed as other illnesses, such as thalamic syndrome. Timely diagnosis of this deficiency is essential, especially in the geriatric population, as it might cause irreversible structural brain damage. This is also presented as elevated levels of homocysteine and methylmalonic acid. Clinically, it presents with the following symptoms: lower sensitivity levels to touch and light, psychosis, paresthesia, anemia, imbalance, fatigue, cognitive disturbances, difficulty remembering, and confusion. Symptoms are usually progressive and worsen over a period of time. In this case report, we present the case of a 62-year-old male with clinical symptoms of numbness and tingling in the right side of the body. The neurological presentations resembled left thalamic infarct, but the underlying reason was methylcobalamin deficiency.