Megaloblastic Anemia Research Articles

Comparative bioavailability study of supplemental oral Sucrosomial® vs. oral conventional vitamin B12 in enhancing circulatory B12 levels in healthy deficient adults: a multicentre, double-blind randomized clinical trial

BackgroundVitamin B12 is essential for neurological function, red blood cell formation, and DNA synthesis. Deficiency can lead to diverse health conditions, including megaloblastic anemia and neurological issues. Oral supplementation is a standard treatment for B12 deficiency. The Sucrosomial® carrier system offers an innovative approach that enhances supplemental nutrient absorption and bioavailability.ObjectivesThis study aimed to compare the effectiveness of oral Sucrosomial® vitamin B12 formulation vs various conventional B12 supplements, randomly selected from local pharmacies, in increasing and maintaining circulatory B12 levels in healthy deficient adults (200–300 pg/mL).MethodsA randomized, double-blind clinical trial was conducted across three centers in Pakistan from April to July 2024. At KEMU, participants received either Sucrosomial® vitamin B12 or Mecogen SL B12; at LRH, Sucrosomial® B12 or B-SUB B12; and at LUMHS, Sucrosomial® B12, Evermin B12, or Neuromax B12. Participants took a daily single dose of 1,000 μg of the assigned B12 formulation for 7 days. Serum B12 levels were measured at baseline (day 0) and on days 1, 3, 5, and 7.ResultsSucrosomial® B12 was significantly more effective than conventional B12 formulations in increasing and maintaining higher serum B12 levels across all time points. At KEMU, it reached a peak concentration of 454 ± 3.9 pg/mL by day 5, compared to 274 ± 11.1 pg/mL with Mecogen SL B12. At LRH, it peaked at 496 ± 34.4 pg/mL by day 5 versus 304 ± 49.4 pg/mL for B-SUB B12. At LUMHS, it reached 592.7 ± 74.3 pg/mL by day 7, compared to 407.24 ± 41.6 pg/mL for Evermin B12 and 263.82 ± 23.8 pg/mL for Neuromax B12. Sucrosomial® B12 was the only formulation to surpass the deficiency-borderline threshold (200–300 pg/mL) within 24 h of the first dose and was well tolerated with no reported side effects.ConclusionSucrosomial® vitamin B12 demonstrated superior efficacy in rapidly and consistently elevating and maintaining higher circulatory B12 levels compared to conventional supplements. Its characteristic absorption mode and proven efficacy suggest it could effectively address B12 deficiency in a broad range of populations, including those with gastrointestinal conditions and pernicious anemia, thereby supporting overall health.Clinical trial registrationclinicaltrials.gov, NCT06376591.

A Comprehensive Analysis of Clinical Presentations, Laboratory Findings, and Etiologies of Pancytopenia: A Tertiary Care Experience.

Background Pancytopenia, while a common manifestation of a multitude of diseases, remains a relatively lesser-researched topic, especially in developing countries. Its management depends largely on identifying the etiology, which can range from simple infections to more sinister causes like leukemia. This study aims to investigate the clinical presentations, hematological findings, and etiologies of pancytopenia in a developing country. Methods A cross-sectional study was conducted at Hayatabad Medical Complex, Peshawar, and included 106 patients who were diagnosed with pancytopenia. Thorough demographic details, histories, clinical examinations, laboratory investigations, bone marrow biopsies, and final diagnoses were recorded and analyzed using statistical tools. Results Pancytopenia was most common in the age group 11-30 years with a male-to-female ratio of 1.4:1. Infections were the leading etiology (17.9%), followed by megaloblastic anemia (17%), hypersplenism (16%), and malignancy (15.1%). Among infections, enteric fever was the most frequently observed cause. The most common presentation was with signs and symptoms of anemia, followed by infections and thrombocytopenia. The most common blood smear finding case-wise was a combination of anisocytosis, microcytosis, and target cells. In patients who underwent bone marrow biopsy, the commonest finding (34%) was suggestive of malignancy with hypercellularity and abnormal cells. Aplastic anemia, hypersplenism, and malignancy were associated with a retic count of <1.5%. Platelet counts of less than 50,000 were associated with the presence of signs and symptoms of thrombocytopenia. Conclusion Pancytopenia can be a presenting feature of a reversible condition like underlying infection and megaloblastic anemia, which contribute a major portion of its etiologies. Early diagnosis and treatment can reverse pancytopenia and prevent over-investigation.

P56 Azathioprine-induced alopecia totalis and knuckle hyperpigmentation in a child with uveitis: test before you leap!

Abstract Introduction Azathioprine is a common disease-modifying anti-rheumatic drug used in non-infectious uveitis. Although unusual, it has been associated with myelosuppression in genetically predisposed individuals who exhibit mutations in thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes. Alopecia secondary to azathioprine treatment is rare, and is an early marker of azathioprine-induced myelosuppression. It usually precedes the onset of myelosuppression, but can also occur simultaneously with pancytopenia. Knuckle pad hyperpigmentation is strongly associated with megaloblastic anemia. We report a patient of panuveitis with both alopecia totalis and knuckle pad hyperpigmentation secondary to azathioprine-induced myelosuppression. Case description A 13-year-old girl presented with acute-onset pain, redness and blurred of both eyes. Ophthalmological evaluation revealed bilateral granulomatous panuveitis. Visual acuity was 6/12 in both eyes, and anterior chamber had 2+ cells. Extensive evaluation for infective and autoimmune causes did not yield any aetiology. Following laboratory tests, a diagnosis of non-infectious panuveitis was made, and oral corticosteroids (2 mg/kg followed by taper) were started. As steroid sparing agents, subcutaneous methotrexate (15 mg/m2/week) and azathioprine (2 mg/kg) were also started after a normal baseline hemogram [Hb: 132 g/L, total leucocyte count (TLC) 12 x 109/L and platelet count: 310 x 109/L]. Two weeks later, she presented with complete loss of hair (alopecia totalis) and knuckle pad hyperpigmentation. Hemogram revealed pancytopenia (Hb: 86 g/L, TLC: 1.7 x 109/L and platelet count: 25 x 109/L). Considering drug-induced myelosuppression, azathioprine was stopped. Subcutaneous injections of Granulocyte colony-stimulating factor (G-CSF) (300 day) were given for two weeks. Mycophenolate mofetil (1200 mg/m2/day) was added. Quantitative polymerase-chain reaction genotyping assay showed a homozygous variant in NUDT15 gene (c.415 C&amp;gt;T). Normalization of hemogram was seen after two weeks (Hb: 120 g/L, TLC: 10.44 x 109/L and platelet count: 199 x 109/L). Reversal of hair loss and knuckle hyperpigmentation was nearly complete at five months and six weeks of follow-up, respectively. Panuveitis remained resolved on methotrexate and mycophenolate, with 6/6 vision and no recurrence at 16-months of follow up. Discussion In India, the prevalence of TPMT mutations (heterozygous 1.2-10%, and homozygous &amp;lt;1%), and NUDT15 mutations (heterozygous 11.6%, and homozygous 1.4%) is low, and the tests are expensive. In routine clinical practice, monitoring of blood counts is recommended in patients on azathioprine (two weekly initially, and then four weekly). Both TPMT and NUDT15 enzymes influence metabolism of azathioprine. Their polymorphisms result in accumulation of active 6-mercaptopurine, which gets converted to 6-thioguanine nucleotide metabolites, producing cytotoxic effects. As a result of disruption in mitotic activity of actively growing hair (anagen), more catagen follicles are seen than anagen, leading to hair loss. While massive hair loss is well recognized secondary to azathioprine, there is no report of knuckle pad hyperpigmentation as a direct adverse reaction of azathioprine. Both knuckle pad hyperpigmentation and azathioprine toxicity are associated with megaloblastic anemia. Knuckle pad hyperpigmentation may be explained by vitamin B12deficiency, with decreased intracellular glutathione. As a result, melanin deposition increases due to loss of tyrosinase inhibition. In addition, melanocyte pigmentary incontinence may also contribute to knuckle pad hyperpigmentation in such cases. Key learning points • While alopecia is often massive, knuckle pad hyperpigmentation may often be overlooked as a clinical sign in patients with azathioprine-induced megaloblastic anemia. Our case highlights the significance of two simple clinical cutaneous signs (alopecia totalis and knuckle pad hyperpigmentation) as clinical indicators of impending, and potentially fatal complication of pancytopenia secondary to azathioprine. In developed countries, genetic analysis is often performed for identifying variants in TPMT and NUDT15 genes before initiation of azathioprine. However, in resource-constrained settings, regular and close monitoring of hemogram, and prompt identification of clinical clues such as alopecia and knuckle pad hyperpigmentation may be a practical method to anticipate azathioprine-induced toxicity including myelosuppression.

Etiological spectrum of pancytopenia in adults based on hematological parameters and bone marrow studies

ABSTRACT Background This study aimed to investigate the demographic, clinical, and diagnostic aspects of adult pancytopenia while exploring its etiological spectrum through hematological parameters and bone marrow studies. Research design and methods This observational study involved 117 adult individuals ranging from 13 to 85 years who presented with pancytopenia. A comprehensive examination of demographic features, hematological parameters, clinical presentations, and physical findings, including liver and spleen characteristics, was conducted. Additionally, serological analyses for HBsAg and Anti HCV were performed. The diagnostic spectrum was determined through bone marrow studies. Results Pancytopenia manifested with varied clinical symptoms, with generalized weakness (72.65%), fever (64.1%), dyspnea (54.70%), bleeding (34.2%), and weight loss (25.6%) being prominent. Physical examination revealed a range of liver and spleen characteristics, with hepatomegaly observed in 32.48% and splenomegaly in 44.4% of cases. Serological findings indicated HBsAg positivity in 8.5% and Anti HCV positivity in 21.37% of cases. The diagnostic distribution encompassed diverse conditions, with aplastic anemia (17.1%), megaloblastic anemia (12.8%), and myelodysplastic syndromes (12.8%) being prevalent. Conclusions This study provides a comprehensive overview of the demographic, clinical, and diagnostic aspects of pancytopenia. The observed prevalence of different diagnoses underscores the necessity of a thorough evaluation, including bone marrow studies, for accurate diagnosis and appropriate management.

Clinical characteristics of megaloblastic anemia with pancytopenia

ABSTRACT Objectives In this study, we aimed to explore the clinical characteristics of patients with megaloblastic anemia and pancytopenia. Methods Data on patient characteristics, laboratory examinations, clinical manifestations, and associated diseases were collected from Changzhou Hospital of Traditional Chinese Medicine. The participants were divided into two groups according to routine blood test results: megaloblastic anemia patients with pancytopenia (Group A) and megaloblastic anemia patients with simple anemia (Group B). Results The number of patients with fever and bleeding in Group A was much higher than that in Group B. Inpatient days and hospitalization costs in Group A were higher than those in Group B. White blood cell count, red blood cell count, haemoglobin level, and platelet count in Group A were lower than those in Group B. There were no significant differences in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and serum levels of lactate dehydrogenase (LDH), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), vitamin B12, folic acid, and ferritin between the two groups. The incidence of associated diseases, particularly pulmonary infections, was significantly higher in Group A than in Group B. There was no significant difference in the degree of bone marrow hyperplasia between the two groups. Conclusion Patients with pancytopenia and megaloblastic anemia often developed infection and bleeding, which caused more severe anemia, higher hospitalization costs, and longer inpatient days. Early diagnosis and active treatment are required to reduce patient complications and costs.

Thiamine-Responsive Megaloblastic Anemia (TRMA) Syndrome mimicking myelodysplastic neoplasm (MDS)

Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive disease with a homozygous or compound-heterozygous mutation in the SLC19A2 gene characterized by megaloblastic anemia, diabetes mellitus (DM), and sensorineural hearing-loss with onset in childhood. Folic acid and vitamin B12 in serum are normal with dysplastic erythropoiesis in the bone marrow often mimicking myelodysplastic neoplasms (MDN) as a potential differential diagnosis. Thiamine substitution leads to normalization of anemia, without effects on hearing-loss or DM. We report about a 38-year-old male patient, presented with a 12-year history of anemia, insulin dependent DM, optic neuropathy and a cataract since early childhood. The laboratory showed megaloblastic anemia. Other values were normal. The bone marrow smear showed dysplastic erythropoiesis with megaloblastic changes, and normal findings in cytogenetic and molecular genetic examinations. Next-generation sequencing based diagnostics revealed a heterozygous missense variant in the SLC19A2 gene on the maternal allele and a 3.4 Mb inversion in the chromosomal region 1q24.2 with breaking points in FAM78B and SLC19A2 on the paternal allele. Treatment with oral thiamine 100 mg daily was initiated, and 12 weeks later Hb levels and bone marrow morphology had normalized. Late-onset TRMA should be considered in adult patients with indicative comorbidities and a typical phenotype, which may mimic features of MDS.

Bone marrow evaluation in a pediatric population with pancytopenia in a tertiary care children’s hospital of Nepal

Background: Pancytopenia, which is characterized by a triad of anemia, leukopenia, and thrombocytopenia, is frequently observed among the pediatric population. This study was carried out to determine the common etiologies of pancytopenia in children through bone marrow aspiration examination. Materials and methods: A one-year retrospective cross-sectional study of 64 cases of pancytopenia in the pediatric population was conducted at the Department of Pathology, Kanti Children’s Hospital, from July 2019 to June 2020. Results: 64 (35.55%) cases underwent bone marrow examination for pancytopenia. The patients' ages ranged from 4 months to 14 years, with a median age of 6.24±1.12 years. The majority of the patients fell into the age group of 1-5 years. The most common cause of pancytopenia was acute leukemia and hypoplastic bone marrow followed by erythroid hyperplasia, leishmaniasis, and megaloblastic anemia. Conclusions: Bone marrow examination is the fundamental diagnostic modality to diagnose the majority of cases of pancytopenia. It is important to consider acute leukemia, hypoplastic bone marrow, and leishmaniasis into account when evaluating pancytopenia in pediatric patients.

A Study of Clinical, Hematological and Biochemical Profiles of Patients with Pancytopenia

This study aimed to investigate patients’ clinical, hematologic, and biochemical profiles with pancytopenia. This prospective observational study was conducted at a tertiary care hospital from January 2019 to June 2020 on 80 patients, 39 (48.7%) were males and 41 (51.2%) were females, over the age of 18 presenting with pancytopenia. All the patients were subjected to thorough clinical and physical examinations. A complete blood count (CBC), peripheral smear examination, bone marrow aspiration, and reticulocyte count were performed. The data was analyzed using the IBM SPSS 20.0 software. Most of the cases had moderate (Hb&lt;7-9.9g/dl) anemia (63.7%, 51/80 cases), while severe anemia (&lt;7g/dl) was seen in 31.2% (25/80) cases, and 5% (04/80) cases showed mild anemia (Hb&lt;10-11.9g/dl). Most patients with severe anemia had vitamin B12 deficiency anemia (12/80), that is, 15%. Macrocytic anemia was noted in preponderance (50% cases, 40/80), whereas microcytic hypochromic and normocytic hypochromic anemia constituted 21.3% (17/80), and dimorphic anemia was seen in 7.5% (06/80) cases. Based on WBC counts, 56.3% of cases (45/80) showed counts between 2000 and 4000 cells/cu.mm, while counts between 1000 and 2000 cells/cu.mm were seen in 31.3% of cases (25/80), and 12.5% of cases (10/80) had counts of &lt;1000 cells/cu.mm. The study highlighted that 28.8% (23/80) had a platelet count between 50,000 and 1 lakh/cu.mm (mild thrombocytopenia), 36.3% (29/80) cases had a platelet count between 20,000 and 50,000/cu.mm (moderate thrombocytopenia), and 35% (28/80) cases had a platelet count less than 20,000/cu.mm (severe thrombocytopenia). The most common diagnosis of bone marrow aspiration was megaloblastic anemia, seen in 50.0% (6/12) cases. Megaloblasts were seen in 50.0% (6/12) cases of megaloblast anemia. The bone marrow aspirate of a patient with dengue fever and malaria showed macrophages containing engulfed red blood cells, lymphocytes, and platelets. Myeloblasts (&gt;20%) were seen in 1 (8.3%) case of AML, and decreased myelopoiesis was seen in 25% of cases (two cases of aplastic anemia and one case of MDS). This study concludes that vitamin B12 deficiency is the most common cause, which is more common in people who are strict vegetarians, with a predominance in the younger age group. The study also emphasized the vitality of the physical findings, detailed primary hematologic and biochemical investigations, and peripheral blood pictures, all of which provide precious information in the work-up of pancytopenia patients.

Comparing Holotranscobalamin and Total Vitamin B12 in Diagnosing Vitamin B12 Deficiency in Megaloblastic Anemia Patients.

Background Megaloblastic anemia is characterized by abnormally large red blood cells caused by a deficiency in either vitamin B12 or folic acid, both of which are essential for DNA synthesis. Vitamin B12 insufficiency can lead to severe neurological damage, making early identification of vitamin B12 deficiency crucial to prevent irreversible harm. Vitamin B12 deficiency results in decreased levels of holotranscobalamin (Holo-TC) and increased levels of methylmalonic acid (MMA). Methylmalonic acid is considered the gold standard for diagnosing B12 deficiency because it is a specific marker that rises when B12 is insufficient, even when serum B12 levels appear normal. Elevated MMA levels reflect impaired B12 metabolism, making it a critical tool for early detection and intervention. Previous research indicates that Holo-TC, the active form of vitamin B12 available to cells, is a more specific diagnostic tool for early vitamin B12 deficiency than total B12. This study aims to determine the diagnostic validity of total vitamin B12 and Holo-TC using MMA as the gold standard in patients with megaloblastic anemia. Methods A total of 95 megaloblastic anemia patients were selected from Jinnah Hospital and Lahore General Hospital, Lahore, Pakistan, after receiving approval from the ethical review committees. This was a cross-sectional study. Whole blood, serum, and urine samples were collected in ethylenediamine tetraacetic acid (EDTA) vials, gel vials, and urine containers, respectively. The EDTA samples were used for complete blood count measurements using a hematology analyzer (Sysmex-XT 1800i, Sysmex America, Inc., Mundelein, IL), while serum and urine samples were employed for the detection of serum folic acid, cobalamin, Holo-TC, and MMA levels through manual enzyme-linked immunosorbent assay (ELISA) techniques. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Holo-TC and cobalamin were calculated. Results The majority of patients fell within the age group of 20-70 years, with 57% of them being females and 43% males; Holo-TC exhibited a sensitivity of 98.9% and specificity of 50.00%, with a PPV of 98.90% and NPV of 50%. Vitamin B12 demonstrated a sensitivity of 63% and specificity of 50%, with a PPV of 98.33% and NPV of 2.85%. The diagnostic accuracy of Holo-TC and vitamin B12 was observed to be 97.8% and 63%, respectively. Conclusions Between the two, Holo-TC displays higher diagnostic accuracy than vitamin B12 and can serve as the primary test for patients suspected of having vitamin B12 deficiency.

The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status.

Vitamin B12 (cobalamin; B12) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B12 deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B12 status include the measurement of serum B12 (also known as total B12 or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B12 status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B12 test, which is readily available and highly automated. In some cases, the sequential use of different B12 status biomarkers or the calculation of a composite B12 status score, derived from a panel of B12 biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarises the utility of B12-related biomarkers and describes approaches to their application and interpretation.

Thiamine Responsive Megaloblastic Anemia and Deafness: A rare case of Roger’s syndrome with successful hearing rehabilitation by Cochlear Implantation

Thiamine Responsive Megaloblastic Anemia and Deafness: A rare case of Roger’s syndrome with successful hearing rehabilitation by Cochlear Implantation

Vitamin B12 responsive developmental and epileptic encephalopathy due to a novel mutation in the FUT2 gene: a case report

BackgroundVitamin B12 deficiency is a recognised cause of neurological manifestations, including peripheral neuropathy, behavioural changes, and seizures. However, developmental and epileptic encephalopathy due to vitamin B12 deficiency is very rare. Here, we report an infant with vitamin B12-responsive developmental and epileptic encephalopathy due to a novel mutation in the fucosyltransferase 2 (FUT2) gene responsible for vitamin B12 absorption.Case presentationAn 11-month-old girl of non-consanguineous parents presented with recurrent episodes of seizures since four months. Her seizures started as flexor epileptic spasms occurring in clusters resembling infantile epileptic spasms syndrome with hypsarrhythmia in the electroencephalogram. She was treated with multiple drugs, including high-dose prednisolone, vigabatrin, sodium valproate, levetiracetam and clobazam, without any response, and she continued to have seizures at 11 months. She had an early developmental delay with maximally achieving partial head control and responsive smile at four months. Her development regressed with the onset of seizure; at 11 months, her developmental age was below six weeks. On examination, she was pale and had generalised hypotonia with normal muscle power and reflexes.Her full blood count and blood picture revealed macrocytic anaemia with oval and round macrocytes. Bone marrow aspiration showed hypercellular marrow erythropoiesis with normoblastic and megaloblastic maturation. Due to the unusual association of refractory epilepsy and megaloblastic anaemia, a rare genetic disease of the vitamin B12 or folate pathways was suspected. The whole exome sequencing revealed a homozygous missense variant in exon 2 of the FUT2 gene associated with reduced vitamin B12 absorption and low plasma vitamin B12 levels, confirming the diagnosis of vitamin B12 deficiency related developmental and epileptic encephalopathy. She was started on intramuscular hydroxocobalamin, for which she showed a marked response with reduced seizure frequency.ConclusionWe report a novel variant in the FUT2 gene associated with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anaemia. This case report highlights the importance of timely genetic testing in children with refractory developmental and epileptic encephalopathy to identify treatable causes.

Novel Homozygous Variant in the SLC19A2 Gene Causing Thiamine Responsive Megaloblastic Anemia Syndrome: A Disease to Be Considered in Diabetes Clinics

Novel Homozygous Variant in the SLC19A2 Gene Causing Thiamine Responsive Megaloblastic Anemia Syndrome: A Disease to Be Considered in Diabetes Clinics

Imerslund-Gräsbeck syndrome in a child with a novel compound heterozygous mutations in the AMN gene: a case report

BackgroundImerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition.Case presentationIn this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018. The child was admitted to the hospital due to a history of anemia persisting for over a month. There was no previous significant medical history. The admission examination revealed megaloblastic anemia with proteinuria. Serum vitamin B12 levels were decreased, while folic acid and renal function were normal. The patient was diagnosed with megaloblastic anemia and started long-term oral vitamin B12 replacement therapy. Throughout the follow-up period, blood tests consistently showed normal results, while proteinuria persisted. In November 2019, the child and her parents underwent whole exome sequencing analysis, which revealed a novel compound heterozygous variant in the AMN gene: c.162 + 1G > A and c.922 C > T (p.Q308X) in the child, c.162 + 1G > A in the father, and c.922 C > T (p.Q308X) in the mother. Therefore, this child was further diagnosed with IGS.ConclusionsIn this case, whole exome sequencing proves to be highly practical in daily healthcare for diagnosing and refining rare or ultra-rare diseases with ambiguous phenotypes or genetic diversity. It is also valuable for prognostic evaluation and personalized management. Additionally, the oral vitamin B12 treatment demonstrated positive clinical effects for the child, offering a new option for patients unable to undergo intramuscular vitamin B12 replacement therapy.

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

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. • 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. • 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.

Severe pancytopenia at the presentation of Imerslund-Gräsbeck syndrome in a 23-month-old Italian boy

BackgroundImerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by megaloblastic anemia due to selective cobalamin malabsorption and benign proteinuria. IGS is caused by a disfunction of the cubam receptor, which mediates the reabsorption of cobalamin in the ileum and the reuptake of albumin in renal proximal tubules.Case presentationWe describe the case of a 23-month-old-italian infant presenting with severe pancytopenia and failure to thrive in whom the diagnosis of IGS was made and vitamin B12 replacement therapy was resolutive. Genetic analysis (NGS with CNV analysis including 214 genes involved in bone marrow failure and anemia), showed the presence of two pathogenetic variants in the AMN gene (c-208–2 A > G and c.1006 + 34_1007-31del). These variants have been previously described in the literature, but their combination has never been reported.ConclusionsImerslund-Gräsbeck syndrome should be considered in the differential diagnosis of children with severe pancytopenia even in those without neurological involvement. This case emphasizes the importance of an early diagnosis and prompt treatment, to prevent irreversible neurological injury.

Updates on the Association Between Anemia and Heart Failure: A Systematic Review.

This systematic review aims to investigate the potential relationship between anemia and heart failure (HF) by summarizing existing literature on the topic. A comprehensive search was performed using four major databases, PubMed, Scopus, Web of Science, and ScienceDirect, to find the relevant literature. Ten studies, including a total of 2,828 participants, with 1,451 (51.3%) males, were included in this review.Iron deficiency anemia was the most prevalent type in the included studies; however, two studies included megaloblastic anemia. The prevalence of anemia in patients diagnosed with HF ranged from 33.3% to 69.8%, with a total prevalence of 1,643 (58.1%). Hypertension, diabetes mellitus, chronic kidney disease, and atrial fibrillation were the most commonly associated comorbidities in patients with HF. Anemia patients had a considerably higher risk of mortality than those without anemia. Anemia served as a marker of disease severity rather than an independent predictor of death in congestive individuals. Anemia was substantially correlated with elevated serum creatinine, left ventricular hypertrophy, and left atrial enlargement. According to the findings of this review, anemia has a significant impact on the prognosis of HF. In patients with HF, anemia may be a reliable indicator of both short- and long-term all-cause mortality as well as the rates of all-cause HF events. Future and ongoing research may provide vital information that may help guide clinical judgments in the future.

Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan, China

ABSTRACT Background Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China. Methods Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA. Results Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months). Conclusions The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.

Clinical and hematological profile of patients with pancytopenia at a tertiary medical center in Ethiopia.

Pancytopenia is an important hematological problem encountered in routine clinical practice associated with a multitude of disease states. The possible causes of pancytopenia can be influenced by geography, socioeconomic conditions, and endemic illnesses. Information regarding the underlying clinical conditions and morphologic features of blood cells of pancytopenia is limited and varied across different regions. Thus, this study was designed to assess the peripheral morphologic features of blood cells and the underlying clinical causes of pancytopenia. A facility-based cross-sectional study was conducted at the Jimma Medical Center hematology laboratory from June 13 to November 13, 2022. A total of 3mL of whole blood was collected from each subject for complete blood count analysis and peripheral blood morphology examination. Data on sociodemographic and clinical conditions were collected from medical records using a checklist. The data were analyzed using Statistical Package for the Social Sciences version 26. A total of 163 patients with pancytopenia were identified within the 5 months. Hyper-reactive malarial splenomegaly was the most prevalent cause (29.4%), followed by megaloblastic anemia (20.2%), chronic liver disease (10.4%), and acute leukemia (8.6%). Anisocytosis was the predominant peripheral blood morphology finding (82.2%), along with microcytosis (49.7%), ovalocytosis (31.3%), and macrocytosis (30.7%). Severe anemia was observed in 57% of cases, whereas the majority (92%) exhibited moderate leukopenia. A significant proportion (42.3%) had a platelet count below 50,000/μL. Unlike previous studies conducted in other parts of the world, this study showed that hyperreactive malarial splenomegaly was the leading cause of pancytopenia. This emphasizes the necessity of considering this condition as a possible cause for pancytopenia, particularly in malaria-endemic areas. The findings of the hematological profiles and peripheral blood morphology strongly suggest that early identification and prompt management of patients with pancytopenia require collaboration between clinical and laboratory investigations.

Frequency of Nutritional Megaloblastic Anemia among Students in Khartoum, Sudan

Background: Megaloblastic anemia is a generative macrocytic anemia characterized by nuclear dysmaturity and the nucleus immature appearance in comparison to the cytoplasm due to a defect in DNA synthesis anemia is a rare ailment in children that is usually caused by a vitamin deficiency or gastrointestinal disorder Objectives: The main objective of this study was to detect the frequency of nutritional megaloblastic anemia in male elementary-school children by measuring hemoglobin (Hb), red blood cell (RBC) count, hematocrit (HCT), and serum folate levels. Methods: This study examined 300 male primary-school children in Khartoum, Sudan. A 2.5-ml of blood was drawn from each student and placed in an ethylene diamine tetra acetic acid (EDTA) vial to estimate the Hb level, RBC count, and HCT using an automated blood analyzer. Another 2.5 mL of blood were drawn from the same students into a plain container and examined for serum folate. Results: The mean Hb was 12.7 g/dl (two standard deviations), the RBC count was 4.71012 cells/L, and the mean packed cell volume (PCV) was 37.2%, and the mean serum folate was 4.4 ng/L. Conclusion: The blood parameters and serum folate were found to be within normal ranges. According to the findings, the nutritional status of the primary-school students was good, and megaloblastic anemia was not common. This type of research should be done on a frequent basis to assess children's nutritional health.