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Italian Journal of Pediatrics Nov 2023Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune...
BACKGROUND
Individuals with thiamine-responsive megaloblastic anemia (TRMA) mainly manifest macrocytic anemia, sensorineural deafness, ocular complications, and nonautoimmune diabetes. Macrocytic anemia and diabetes may be responsive to high-dosage thiamine treatment, in contrast to sensorineural deafness. Little is known about the efficacy of thiamine treatment on ocular manifestations.
CASES PRESENTATION
Our objective is to report data from four Italian TRMA patients: in Cases 1, 2 and 3, the diagnosis of TRMA was made at 9, 14 and 27 months. In 3 out of 4 subjects, thiamine therapy allowed both normalization of hyperglycemia, with consequent insulin suspension, and macrocytic anemia. In all Cases, thiamine therapy did not resolve the clinical manifestation of deafness. In Cases 2 and 3, follow-up showed no blindness, unlike Case 4, in which treatment was started for megaloblastic anemia at age 7 but was increased to high doses only at age 25, when the genetic diagnosis of TRMA was performed.
CONCLUSIONS
Early institution of high-dose thiamine supplementation seems to prevent the development of retinal changes and optic atrophy in TRMA patients. The spectrum of clinical manifestations is broad, and it is important to describe known Cases to gain a better understanding of this rare disease.
Topics: Humans; Child; Adult; Diabetes Mellitus; Hearing Loss, Sensorineural; Thiamine; Anemia, Megaloblastic; Early Diagnosis; Deafness
PubMed: 38037112
DOI: 10.1186/s13052-023-01553-1 -
Medicine Dec 2023Anorexia nervosa is characterized by an extreme fear of weight gain. Clinicians often prescribe meal replacement shakes if patients are unable or unwilling to consume...
RATIONALE
Anorexia nervosa is characterized by an extreme fear of weight gain. Clinicians often prescribe meal replacement shakes if patients are unable or unwilling to consume typical foods. However, these shakes sometimes lack essential micronutrients, such as selenium, which may lead to health risks. Moreover, selenium deficiency induces macrocytic anemia. Herein, we present a case of a patient with anorexia nervosa with macrocytic anemia due to selenium deficiency, which was alleviated by selenium supplementation.
PATIENT CONCERNS
An 18-year-old female was admitted to our hospital. The patient was diagnosed with anorexia nervosa. Ultimately, she was unable to walk independently because of fatigue and electrolyte disturbances.
CLINICAL FINDINGS
On admission, the height, weight, and body mass index of the patient were 158.5 cm, 27.1 kg, and 10.8, respectively. Our treatment for anorexia nervosa showed relative effectiveness, and the patient's body weight recovered to 29.2 kg by day 60. However, the mean corpuscular volume increased from day 20, suggesting macrocytic anemia.
DIAGNOSES, INTERVENTIONS, AND OUTCOMES
Despite our vitamin B12 and folic acid supplementation interventions, the mean corpuscular volume continued to rise. On day 60, the patient was diagnosed with selenium deficiency, and selenium administration of 100 μg/day was initiated.
OUTCOMES
The macrocytic anemia in the patient was alleviated, and treatment for anorexia nervosa was continued in our hospital.
LESSONS
To the best of our knowledge, this is the first case of macrocytic anemia induced by selenium deficiency with anorexia nervosa comorbidity, underscoring the importance of selenium supplementation in patients with anorexia nervosa, especially in those with macrocytic anemia.
Topics: Female; Humans; Adolescent; Anorexia Nervosa; Selenium; Malnutrition; Body Mass Index; Anemia, Macrocytic
PubMed: 38134070
DOI: 10.1097/MD.0000000000036740 -
Journal of Investigational Allergology... Jul 2023Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID),...
BACKGROUND AND OBJECTIVE
Cartilage-hair hypoplasia (CHH) syndrome is a rare autosomal recessive syndrome associated with skeletal dysplasia, varying degrees of combined immunodeficiency (CID), short stature, hair hypoplasia, macrocytic anemia, increased risk of malignancies, and Hirschsprung disease. To provide clinical and immunological insights obtained from 2 unrelated patients who displayed clinical characteristics of CHH.
METHODS
Two patients with suspected CHH syndrome due to skeletal dysplasia and immunodeficiency underwent an immunological and genetic work-up using flow cytometry, next-generation sequencing (NGS) of the immune repertoire, and Sanger sequencing to identify the underlying defects.
RESULTS
Patient 1 presented with low birth weight and skeletal dysplasia. Newborn screening was suggestive of T-cell immunodeficiency, as T-cell receptor excision circle levels were undetectable. Both the T-cell receptor (TCR) Vß and TCR-g (TRG) repertoires were restricted, with evidence of clonal expansion. Genetic analysis identified compound heterozygous RMRP variants inherited from both parents. Patient 2 presented with recurrent lung and gastrointestinal infections, skeletal dysplasia, failure to thrive, and hepatomegaly. The polyclonal pattern of the TCRß repertoire was normal, with only slight overexpression of TCR-ßV20 and restricted expression of Vßs. TRG expressed a normal diverse repertoire, similar to that of the healthy control sample. Genetic analysis identified biallelic novel regulatory variants in RMRP. Both parents are carriers of this mutation.
CONCLUSION
Our findings demonstrate how the immunological work-up, supported by genetic findings, can dramatically change treatment and future outcome in patients with the same clinical syndrome.
Topics: Infant, Newborn; Humans; Hirschsprung Disease; Immunologic Deficiency Syndromes; Hair; Receptors, Antigen, T-Cell; Disease Progression
PubMed: 35166674
DOI: 10.18176/jiaci.0792 -
Pediatric Nephrology (Berlin, Germany) Sep 2023
Topics: Male; Humans; Anemia; Diabetes Mellitus; Proteinuria
PubMed: 37084135
DOI: 10.1007/s00467-023-05970-6 -
Pediatric Nephrology (Berlin, Germany) Sep 2023
Topics: Male; Humans; Anemia; Proteinuria; Diabetes Mellitus
PubMed: 37084136
DOI: 10.1007/s00467-023-05972-4 -
EMBO Reports May 2024Microcephaly is a common feature in inherited bone marrow failure syndromes, prompting investigations into shared pathways between neurogenesis and hematopoiesis. To...
Microcephaly is a common feature in inherited bone marrow failure syndromes, prompting investigations into shared pathways between neurogenesis and hematopoiesis. To understand this association, we studied the role of the microcephaly gene Mcph1 in hematological development. Our research revealed that Mcph1-knockout mice exhibited congenital macrocytic anemia due to impaired terminal erythroid differentiation during fetal development. Anemia's cause is a failure to complete cell division, evident from tetraploid erythroid progenitors with DNA content exceeding 4n. Gene expression profiling demonstrated activation of the p53 pathway in Mcph1-deficient erythroid precursors, leading to overexpression of Cdkn1a/p21, a major mediator of p53-dependent cell cycle arrest. Surprisingly, fetal brain analysis revealed hypertrophied binucleated neuroprogenitors overexpressing p21 in Mcph1-knockout mice, indicating a shared pathophysiological mechanism underlying both erythroid and neurological defects. However, inactivating p53 in Mcph1 mice failed to reverse anemia and microcephaly, suggesting that p53 activation in Mcph1-deficient cells resulted from their proliferation defect rather than causing it. These findings shed new light on Mcph1's function in fetal hematopoietic development, emphasizing the impact of disrupted cell division on neurogenesis and erythropoiesis - a common limiting pathway.
Topics: Animals; Erythropoiesis; Microcephaly; Mice; Mice, Knockout; Cell Cycle Proteins; Tumor Suppressor Protein p53; Cyclin-Dependent Kinase Inhibitor p21; Cytoskeletal Proteins; Mutation; Anemia, Macrocytic; Cell Differentiation; Erythroid Precursor Cells
PubMed: 38605277
DOI: 10.1038/s44319-024-00123-8 -
Clinical Pediatrics Jun 2024
PubMed: 38840508
DOI: 10.1177/00099228241257097 -
Journal of Medical Case Reports Jul 2023Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as:...
BACKGROUND
Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease.
CASE PRESENTATION
A 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient's initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms.
CONCLUSION
This case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms.
Topics: Humans; Child; Female; Young Adult; Adult; Diabetes Mellitus, Type 1; Anemia, Iron-Deficiency; Celiac Disease; Gastritis; Autoimmune Diseases; Vitamin B 12 Deficiency; Vitamin B 12; Diarrhea; Pain; Insulins
PubMed: 37507704
DOI: 10.1186/s13256-023-04039-0 -
American Journal of Clinical Pathology Jun 2024VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene....
Comprehensive morphologic characterization of bone marrow biopsy findings in a large cohort of patients with VEXAS syndrome: A single-institution longitudinal study of 111 bone marrow samples from 52 patients.
OBJECTIVES
VEXAS syndrome is an adult-onset autoinflammatory disease caused by a somatic pathogenic mutation in the UBA1 (ubiquitin-like modifier activating enzyme 1) gene. Patients present with rheumatologic manifestations and cytopenias and may have an increased predisposition to myelodysplastic syndrome (MDS) and plasma cell neoplasms. Prior studies have reported on the peripheral blood and bone marrow findings in patients with VEXAS syndrome. Due to the protean clinical presentation and lack of specificity of morphologic features (eg, vacuoles in early erythroid and granulocytic precursors), an optimal screening methodology to identify these patients in a timely fashion is desirable.
METHODS
To further evaluate and describe the salient diagnostic morphologic features in VEXAS syndrome, we carried out a comprehensive study of the largest single-institution cohort to date. Diagnostic and follow-up bone marrow biopsy specimens from 52 male patients with molecularly identified VEXAS syndrome underwent central review.
RESULTS
Cytopenias were common in all cases, primarily macrocytic anemia, monocytopenia, and thrombocytopenia. Bone marrow aspirate and biopsy were often hypercellular, with an increased myeloid/erythroid ratio, granulocytic hyperplasia with left shift, erythroid left shift, and megakaryocyte hyperplasia, which exhibited a range of striking morphologic findings. Distinctly vacuolated myeloid and erythroid precursors were seen in more than 95% of cases.
CONCLUSIONS
Our data reveal potential novel diagnostic features, such as a high incidence of monocytopenia and distinct patterns of atypical megakaryopoiesis, that appear different from dysmegakaryopoiesis typically associated with MDS. In our experience, those findings are suggestive of VEXAS, in the appropriate clinical context.
Topics: Humans; Male; Middle Aged; Bone Marrow; Adult; Aged; Longitudinal Studies; Biopsy; Ubiquitin-Activating Enzymes; Myelodysplastic Syndromes; Young Adult; Aged, 80 and over; Cohort Studies; Female; Mutation; Thrombocytopenia
PubMed: 38413044
DOI: 10.1093/ajcp/aqad186 -
Nederlands Tijdschrift Voor Geneeskunde Dec 2023Anaemia can be subdivided into microcytic, normocytic and macrocytic categories, which give direction to the investigation to identify the cause of the anaemia. However,...
Anaemia can be subdivided into microcytic, normocytic and macrocytic categories, which give direction to the investigation to identify the cause of the anaemia. However, this is not always straightforward, as this case illustrates. A 73-year-old man with normocytic anaemia appeared to have both beta thalassemia trait (microcytic) and myelodysplastic syndrome (usually macrocytic). This led to a mixture of red blood cells of different sizes and an average normal MCV. The manual differentiation of the blood smear was helpful to find the right diagnosis.
Topics: Male; Humans; Aged; Anemia; Erythrocytes; Causality
PubMed: 38175604
DOI: No ID Found