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BMC Pulmonary Medicine Mar 2024Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is... (Review)
Review
BACKGROUND
Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed.
CASE DESCRIPTION
Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia.
CONCLUSIONS
This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.
Topics: Humans; Female; Middle Aged; Erlotinib Hydrochloride; Anemia; Anemia, Megaloblastic; Adenocarcinoma of Lung; ErbB Receptors; Lung Neoplasms; Vitamin B 12
PubMed: 38448889
DOI: 10.1186/s12890-024-02935-9 -
Journal of Pediatric Endocrinology &... Apr 2024Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency...
OBJECTIVES
Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected.
CASE PRESENTATION
Mutation analysis revealed one unreported pathogenic variant in the gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment.
CONCLUSIONS
This is the first report of Argentinean patients with TC deficiency that detected a new variant in NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.
Topics: Infant, Newborn; Humans; Vitamin B 12; Transcobalamins; Retrospective Studies; Vitamin B 12 Deficiency; Anemia, Macrocytic; Amino Acid Metabolism, Inborn Errors; Early Diagnosis
PubMed: 38436354
DOI: 10.1515/jpem-2023-0577 -
Tropical Doctor Jul 2024Vitamin B12 and folate deficiency are reversible causes of megaloblastic anemia Strict vegetarians are at risk of megaloblastic anemia due to low cobalamin in their diet...
Vitamin B12 and folate deficiency are reversible causes of megaloblastic anemia Strict vegetarians are at risk of megaloblastic anemia due to low cobalamin in their diet Knuckle hyperpigmentation in patients with megaloblastic anemia is due to excess melanin synthesis in skin. Here we present a case of a young vegetarian male with megaloblastic anemia with knuckle hyperpigmentation managed successfully with intravenous followed by oral vitamin b12 and folate supplementation.
Topics: Humans; Male; Vitamin B 12 Deficiency; Hyperpigmentation; Vitamin B 12; Anemia, Megaloblastic; Folic Acid; Adult; Dietary Supplements; Diet, Vegetarian; Treatment Outcome
PubMed: 38419508
DOI: 10.1177/00494755241234081 -
Journal of Ayub Medical College,... 2023Thiamine-responsive megaloblastic anaemia (TRMA) is characterized by the classic trio of diabetes mellitus, sensorineural hearing loss, and megaloblastic anaemia,...
Thiamine-responsive megaloblastic anaemia (TRMA) is characterized by the classic trio of diabetes mellitus, sensorineural hearing loss, and megaloblastic anaemia, typically emerging subtly between infancy and adolescence. Administration of high-dose thiamine often yields improvements in anaemia and occasionally in diabetes. Uncommon manifestations include optic atrophy, congenital heart defects, short stature, and stroke. In this specific case, a 5-year-old diagnosed with insulin-dependent diabetes mellitus (IDDM) since the age of one presented with symptoms such as polyuria, fever, and vomiting, revealing an HbA1c of 10.64. Further examinations disclosed compromised hearing and vision. A negative antibody workup and a thyroid profile indicating hypothyroidism prompted additional investigations, including Brainstem Evoked Response Audiometry (BERA) and retinal examination, confirming bilateral sensorineural hearing loss and maculopathy, respectively. A comprehensive blood count unveiled megaloblastic anaemia. Genetic profiling confirmed a homozygous mutation in the SLC19A2 gene, thus diagnosing TRMA. An early diagnosis, coupled with genetic confirmation, enables timely intervention, with patients responding positively to high-dose thiamine. Genetic counselling plays a pivotal role in enlightening families about the disease and its inheritance patterns, fostering awareness and understanding.
Topics: Humans; Child, Preschool; Thiamine Deficiency; Thiamine; Anemia, Megaloblastic; Hearing Loss, Sensorineural; Hypothyroidism; Diabetes Mellitus; Membrane Transport Proteins
PubMed: 38406914
DOI: 10.55519/JAMC-S4-12486 -
Indian Journal of Pathology &... Sep 2023Rogers syndrome is an extremely rare autosomal recessive syndrome of which only 100 cases are known worldwide. It is characterized by thiamine-responsive megaloblastic...
Rogers syndrome is an extremely rare autosomal recessive syndrome of which only 100 cases are known worldwide. It is characterized by thiamine-responsive megaloblastic anaemia, diabetes mellitus and sensorineural deafness. It results from the deficiency of a thiamine transporter protein. We herein report a 16-year-old Indian male referred to our centre with complaints of refractory anaemia, deafness, diabetes pulmonary arterial hypertension and tricuspid regurgitation. Based on the clinical features and haematologic picture and dramatic response of anaemia to thiamine therapy the possibility of a TRMA was considered. Sequencing analysis for TRMA revealed a homozygous c.242dup (p.Tyr81Ter) mutation of the SLC19A2 gene.
PubMed: 38391342
DOI: 10.4103/ijpm.ijpm_287_23 -
Folate depletion induces erythroid differentiation through perturbation of de novo purine synthesis.Science Advances Feb 2024Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as...
Folate, an essential vitamin, is a one-carbon acceptor and donor in key metabolic reactions. Erythroid cells harbor a unique sensitivity to folate deprivation, as revealed by the primary pathological manifestation of nutritional folate deprivation: megaloblastic anemia. To study this metabolic sensitivity, we applied mild folate depletion to human and mouse erythroid cell lines and primary murine erythroid progenitors. We show that folate depletion induces early blockade of purine synthesis and accumulation of the purine synthesis intermediate and signaling molecule, 5'-phosphoribosyl-5-aminoimidazole-4-carboxamide (AICAR), followed by enhanced heme metabolism, hemoglobin synthesis, and erythroid differentiation. This is phenocopied by inhibition of folate metabolism using the inhibitor SHIN1, and by AICAR supplementation. Mechanistically, the metabolically driven differentiation is independent of mechanistic target of rapamycin complex 1 (mTORC1) and adenosine 5'-monophosphate-activated protein kinase (AMPK) and is instead mediated by protein kinase C. Our findings suggest that folate deprivation-induced premature differentiation of erythroid progenitor cells is a molecular etiology to folate deficiency-induced anemia.
Topics: Mice; Humans; Animals; Folic Acid; Cell Differentiation; Cell Line; Mechanistic Target of Rapamycin Complex 1; Purines
PubMed: 38295180
DOI: 10.1126/sciadv.adj9479 -
Cureus Dec 2023Vitamin B12 deficiency is a well-known and overall common disease. While the etiology of vitamin B12 deficiency varies from post-surgical changes to inadequate dietary...
Vitamin B12 deficiency is a well-known and overall common disease. While the etiology of vitamin B12 deficiency varies from post-surgical changes to inadequate dietary consumption, pernicious anemia should be considered as it is a common cause. Pernicious anemia is an autoimmune atrophic gastritis impairing the absorption of vitamin B12. Manifestations include neurological changes, macrocytic anemia, glossitis, and nail changes. Hemolytic anemia is an unusual complication of vitamin B12 deficiency and an even more unusual initial presentation. This case identifies a patient with previously undiagnosed pernicious anemia with severe vitamin B12 deficiency compounded by hemolytic anemia as the presenting symptom. Overall, this case highlights the importance of considering vitamin B12 deficiency-related hemolytic anemia and the need for further research into the causes and pathophysiology of vitamin B12-induced hemolysis due to its potential for fatal outcomes despite being easily treatable with cost-effective methods to treat.
PubMed: 38226075
DOI: 10.7759/cureus.50534 -
Pediatric Blood & Cancer Apr 2024
Topics: Humans; Child; Homocystinuria; Anemia, Megaloblastic; Vitamin B 12
PubMed: 38217084
DOI: 10.1002/pbc.30867 -
Mymensingh Medical Journal : MMJ Jan 2024Pernicious anemia is an autoimmune disease leading to impaired absorption of dietary cobalamin. Patients with pernicious anemia can present with multiple hematological,...
Pernicious anemia is an autoimmune disease leading to impaired absorption of dietary cobalamin. Patients with pernicious anemia can present with multiple hematological, neurological and gastrointestinal complaints. Herein, we have a case of pernicious anemia presenting with alternating bowel habit. This was challenging and unique as the patient didn't have any usual condition responsible for alternating bowel habit and it is not reported in cases of pernicious anemia either. The case is a 46-year-old male who was admitted with alternating bowel habit, paresthesia and fever for the last 6 months. Patient was found to be severely anemic. After full workup, he was diagnosed with pernicious anemia. The patient was treated with IM Injections of Vitamin B12. After 3 months of discharge, the patient was free of all the symptoms. This case emphasizes the importance of investigating anemic patients with alternating bowel habit for pernicious anemia and also the need to exclude other causes of this symptom before labeling it as pernicious anemia only.
Topics: Male; Humans; Middle Aged; Anemia, Pernicious; Vitamin B 12; Autoimmune Diseases; Paresthesia
PubMed: 38163808
DOI: No ID Found