Transcobalamin deficiency is an autosomal recessive disease caused by pathogenic variants in the TCN2 gene. It is a multisystem disorder, with haematological manifestations such as megaloblastic anaemia and pancytopenia. Neurological manifestations include ataxia, hypotonia and neuropathy. Gastrointestinal and immunological clinical presentations include diarrhoea, cytomegalovirus (CMV) colitis, failure to thrive and recurrent infections.We report a female toddler who initially presented at early infancy with severe failure to thrive, diarrhoea, CMV colitis and pancytopenia and was initially diagnosed with childhood myelodysplastic syndrome based on bone marrow examination and a strong family history in her cousins. Whole exome sequencing revealed a homozygous pathogenic variant, c.927_930del (p.(Cys309Trpfs*50)), in the TCN2, consistent with a diagnosis of autosomal recessive transcobalamin deficiency. Treatment with parenteral hydroxocobalamin resulted in dramatic improvement in her symptoms and resolved the myelodysplastic changes.

Osmotic demyelination syndrome (ODS) is a rare neurological disorder typically associated with rapid correction of hyponatremia, whereas alcohol-related peripheral neuropathy (ALN) is a common complication of chronic alcohol use. The coexistence of ODS and ALN is uncommon and may obscure timely diagnosis. We report the case of a 51-year-old man with a long-standing history of alcohol dependence who presented to the emergency department with vomiting and diarrhea persisting for six days. Laboratory tests revealed hyponatremia, macrocytic anemia, thrombocytopenia, and electrolyte imbalances. Neurological examination demonstrated distal paresthesia, diminished reflexes in the lower extremities, and positive Babinski and Chaddock signs. MRI revealed a hyperintense trident-shaped lesion in the pons consistent with ODS. These findings suggested the concomitant presence of ALN and ODS. The patient was treated conservatively with vitamin supplementation, careful correction of electrolytes, and gradual nutritional rehabilitation. Sodium levels normalized without the need for rapid correction, and the patient's symptoms improved, leading to discharge on the eighth hospital day. This case underscores two essential points: ODS was identified before any documented rapid in-hospital correction of hyponatraemia, and alcohol-dependent patients may present with overlapping features of ALN and ODS. Recognition of pyramidal signs is critical for differentiating central from peripheral neurological complications in this population. Clinicians should maintain a high index of suspicion for concomitant ODS in alcohol-dependent patients with neuropathy, particularly when pyramidal signs are present.

Pernicious anemia (PA) is an autoimmune cause of vitamin B12 deficiency, often secondary to chronic atrophic gastritis, which increases the risk of gastric malignancies. Early signs, like mild macrocytosis, are frequently overlooked, especially in patients with other risk factors such as long-term metformin use. We present a case illustrating the full clinical trajectory from long-standing, unexplored macrocytosis to severe anemia, ultimately leading to the diagnosis of PA and detection of early-stage gastric adenocarcinoma on surveillance esophagogastroduodenoscopy (EGD). Informed consent was obtained from the patient to publish the case. The patient was a 59-year-old man with type 2 diabetes, treated with metformin 2 g daily for over four years, who presented with severe symptomatic macrocytic anemia after approximately one year of unexplored macrocytosis on routine laboratory testing. Evaluation revealed profound vitamin B12 deficiency with evidence of hemolysis, and serologic testing confirmed PA. Surveillance EGD identified a gastric polyp, which was resected for histopathologic evaluation. Examination of the lesion revealed a moderately differentiated adenocarcinoma with associated high-grade dysplasia and submucosal invasion. Random gastric biopsies demonstrated chronic inflammation with focal atypia and were negative for Helicobacter pylori. Subsequent staging investigations confirmed stage I disease (cT1b, cN0, and cM0). The patient underwent partial gastrectomy and continued intramuscular vitamin B12 therapy, with excellent clinical recovery and no evidence of recurrent disease on follow-up. Our case highlights that persistent macrocytosis should not be overlooked, particularly in patients with risk factors for vitamin B12 deficiency such as long-term metformin use. Early evaluation may uncover important underlying diagnoses such as PA, prevent severe hematologic complications, and facilitate detection of associated gastric malignancies at a potentially curable stage.

Vitamin B12 deficiency is a common yet frequently underrecognized nutritional disorder with important public health implications, particularly in low- and middle-income countries where maternal deficiency, vegetarian dietary practices, and food insecurity are prevalent. In children, deficiency may lead to irreversible neurodevelopmental impairment, growth failure, and hematological abnormalities, making early recognition essential. The clinical spectrum ranges from asymptomatic biochemical deficiency and isolated macrocytic anemia to developmental regression, seizures, movement disorders, peripheral neuropathy, and pancytopenia, with neurological manifestations often preceding hematological changes. Diagnosis requires integration of clinical features with laboratory evaluation, including complete blood count, peripheral smear, serum vitamin B12 estimation, and functional biomarkers such as methylmalonic acid and homocysteine, which improve diagnostic accuracy in borderline or atypical cases. Molecular testing has expanded the identification of inherited disorders affecting vitamin B12 absorption and metabolism, enabling timely lifelong management. Prompt replacement therapy is the cornerstone of treatment and should not be delayed when clinical suspicion is high. Oral supplementation is effective for most dietary deficiencies, whereas parenteral therapy is indicated for severe anemia, neurological involvement, malabsorption, or inherited cobalamin disorders. Early treatment results in rapid hematological recovery, but delayed intervention may leave permanent neurological sequelae despite biochemical correction. Beyond individual patient care, strengthening maternal nutrition, targeted screening of high-risk populations, food fortification, and public awareness are critical strategies to reduce the burden of vitamin B12 deficiency and prevent avoidable disability. This review summarizes current evidence on the diagnosis and treatment of pediatric vitamin B12 deficiency and highlights practical approaches for improving clinical outcomes.

Anemia is a common condition in older adults and is associated with increased morbidity, geriatric syndromes, and functional decline. We report the case of an 86-year-old woman who presented with severe anemia accompanied by neurologic, hematologic, and oral manifestations, in whom vitamin B12 deficiency was identified as the underlying etiology. Following targeted parenteral cyanocobalamin therapy, the patient demonstrated marked hematologic recovery and substantial improvement in gait, strength, and independence in basic activities of daily living, as documented through a comprehensive geriatric assessment. This case underscores the importance of recognizing vitamin B12 deficiency as an underdiagnosed yet reversible cause of anemia and functional deterioration in older adults and highlights the essential role of comprehensive geriatric assessment in detecting reversible contributors to frailty and enabling timely, individualized intervention.

Pulmonary hypertension (PH) is uncommon in myopathy, encephalopathy, lactic acidosis, and stroke-like (MELAS) and its hemodynamics are poorly described. A 2-year-old Japanese girl was referred to our hospital with PH diagnosed during pneumonia treatment. Cardiac catheterization revealed PH with a high cardiac output. The patient was diagnosed with MELAS based on multiorgan involvement and the detection of an m.3243A>G mutation. PH therapy was partially effective, and oxygen supplementation may help improve PH without worsening the high cardiac output.

Background Anemia is a common and often underrecognized comorbidity in patients with hypothyroidism. Its etiology is multifactorial and is influenced by thyroid hormone deficiency, nutritional status, and concomitant chronic conditions. Understanding the prevalence, hematological patterns, and predictors of anemia in patients with hypothyroidism is necessary to improve clinical outcomes. This study aimed to assess the prevalence of anemia, describe its types and features, examine its association with thyroid hormone status, and identify the independent predictors of anemia in patients with hypothyroidism. Materials and methods A retrospective study was conducted in 444 patients diagnosed with hypothyroidism. Demographic, clinical, and laboratory data were extracted from the electronic medical records. Hematological indices were compared between the anemic and non‑anemic groups using independent t-tests and chi-square tests. Multivariate logistic regression was performed to identify the independent predictors of anemia after adjusting for age, sex, diabetes, and hypertension. Results Anemia was present in 112 (25.2%) patients. In anemic patients, the most common type was normocytic anemia, occurring in 64 (57.1%), followed by microcytic anemia in 46 (41.1%) and macrocytic anemia in two (1.8%). Patients with anemia had significantly higher platelet counts than those without anemia (p < 0.001). Markers of thyroid function (TSH, T3, and T4) did not differ significantly between the groups (p > 0.05). Multivariate analysis revealed that female sex (adjusted odds ratio (AOR) = 3.210, 95% confidence interval (CI): 1.323-7.789, p = 0.010) and the presence of chronic diseases (AOR = 3.458, 95% CI: 1.829-6.536, p < 0.001) were independent predictors of anemia. Conclusions One in four patients with hypothyroidism had anemia, and the most common type was normocytic anemia. No significant differences in thyroid hormone levels were observed between anemic and non-anemic patients. Female sex and chronic diseases were significant risk factors for anemia, emphasizing the importance of targeted screening and comprehensive evaluation of these subgroups. Early diagnosis and treatment of anemia may improve overall clinical outcomes in patients with hypothyroidism.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly described inflammatory disease characterized by recurrent autoimmune manifestations, such as chondritis and uveitis, in the setting of classic laboratory abnormalities, including elevated inflammatory markers and macrocytic anemia. It is caused by an acquired mutation in the UBA1 gene within the myeloid lineage, ultimately resulting in cell death and systemic inflammation. Timely diagnosis can help expedite treatment and encourage monitoring for complications of the disease, most notably a predilection to infections. A 77-year-old male presented to the emergency room due to new-onset fevers and shortness of breath. His history was notable for six months of non-specific symptoms such as fatigue and weight loss, as well as recurrent inflammatory syndromes, including uveitis and joint swelling. At one point, he was treated empirically with steroids due to concern for giant cell arteritis; however, biopsy did not confirm this diagnosis. Labs were notable for significantly elevated inflammatory markers and a macrocytic anemia. His hospitalization was notable for acute hypoxemic respiratory failure requiring high-flow nasal cannula oxygen. His condition improved with broad-spectrum antibiotics, and he was ultimately diagnosed with Legionella pneumonia when Legionella PCR from pleural fluid returned positive. Prior to discharge, genetic testing for the UBA1 gene mutation and bone marrow biopsy demonstrating vacuolization of myeloid precursors confirmed the diagnosis of VEXAS syndrome. He was started on prednisone and azacitidine in the outpatient setting, which led to significant improvement in symptoms, inflammatory markers, and cell counts.

Rothia mucilaginosa is an uncommon but increasingly recognized opportunistic pathogen capable of causing invasive infection, particularly in patients with prosthetic material and immunocompromised states. Rarely, severe systemic infections may present with thrombotic microangiopathy-like syndromes mimicking thrombotic thrombocytopenic purpura (TTP), creating significant diagnostic uncertainty. We present a case of fulminant Rothia mucilaginosa prosthetic valve infective endocarditis initially presenting as a TTP/disseminated intravascular coagulation (DIC) mimic in a 60-year-old man with severe thrombocytopenia, schistocytosis, hemolytic anemia, encephalopathy, and intracranial hemorrhage. Due to concern for evolving TTP, emergent plasmapheresis and corticosteroids were initiated prior to identification of the underlying infectious process. Blood cultures subsequently grew Rothia mucilaginosa, and transesophageal echocardiography demonstrated prosthetic valve endocarditis. The patient's course was complicated by progressive bilateral intracranial hemorrhage, septic emboli, and catastrophic neurologic deterioration despite aggressive multidisciplinary management. This case highlights the diagnostic challenge of distinguishing primary TTP from infection-associated thrombotic microangiopathy and emphasizes the importance of maintaining a broad differential diagnosis in patients presenting with thrombocytopenia, schistocytosis, neurologic dysfunction, and sepsis physiology, particularly in the setting of prosthetic cardiac valves.

Myelodysplastic syndrome (MDS) is a rare group of diseases defined by cytopenias, abnormal cellular morphology and various symptoms including anemia, infections, and bleeding. This wide array of nonspecific symptoms creates a challenge in diagnosing MDS, especially in a rural setting. In this case study we present an 81-year-old female who presented to a rural family medicine clinic for evaluation of a severe macrocytic anemia that persisted despite repeated transfusions. The patient was evaluated with a variety of labs including complete blood count, vitamin levels, endocrine evaluation and immunoglobulins before being referred to hematology for a bone marrow biopsy and diagnosis of MDS. This case highlights the challenges of diagnosing MDS in a rural setting and discusses methods that can be used by primary care providers to differentiate MDS from other hematological conditions prior to a subspecialist referral.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described autoinflammatory disorder caused by somatic UBA1 mutations in hematopoietic stem and progenitor cells. It typically presents in older males with treatment-refractory systemic inflammation and hematologic abnormalities. We report a case of a 92-year-old male who presented with auricular chondritis and other systemic symptoms, including inflammatory arthritis, conjunctivitis, and a diffuse rash. Laboratory evaluation revealed macrocytic anemia and elevated inflammatory markers, with largely negative autoimmune serologies aside from a mildly elevated rheumatoid factor. Bone marrow analysis showed cytoplasmic vacuolization of myeloid and erythroid precursors, and genetic testing identified a UBA1 p.Met41Thr pathogenic variant, confirming the diagnosis of VEXAS syndrome. Treatment with oral prednisone, monthly tocilizumab infusions, and supportive epoetin alfa-epbx led to significant clinical improvement. This case underscores the importance of considering VEXAS syndrome in elderly male patients presenting with unexplained systemic inflammation, chondritis, and cytopenias, and highlights the critical roles of early recognition, multidisciplinary evaluation, and timely genetic testing in diagnosis and management.

Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by biallelic loss of function variants in the SLC19A2 gene. It typically presents with a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. In this work, we analyzed ten children with suspected TRMA: nine exhibited the full triad and one, a younger sibling of a patient with full triad, did not develop hearing loss by the age of 18 months. All patients became transfusion-independent on high-dose thiamine therapy. Whole-genome sequencing identified homozygosity for the canonical splice variant SLC19A2 c.1223+1G>A in eight patients. One patient was homozygous for a known SLC19A2 c.196G>T variant, and the other was compound heterozygous for two novel variants, c.120C>G and c.584T>C. All patients with the SLC19A2 c.1223+1G>A variant were ethnic Ingush. In the reference Ingush cohort, 9/328 unrelated adults were c.1223+1G>A carriers (heterozygous carrier frequency 2.7%; carrier frequency ≈ 1/36), and shared a 2.3 Mb ATP1B1-FMO2 haplotype on chromosome 1, demonstrating a strong founder effect. These findings identify Ingushetia as a new TRMA-endemic region and support targeted SLC19A2 screening and early thiamine therapy in patients with macrocytic anemia and diabetes of unclear origin in this population.