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Blood Cells, Molecules & Diseases Nov 2023Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes...
BACKGROUND
Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes undiagnosed anemia a unique clinical entity in tertiary hematology centers. In this study, we aim at plotting a stepwise diagnostic approach in children with undiagnosed anemia while identifying indications for genetic testing.
PATIENTS AND METHODS
A one-year cross-sectional study involved 44 children and adolescents with undiagnosed anemia after undergoing an initial routine panel of investigations. They were classified based on mean corpuscular volume (MCV) into 3 groups: microcytic (n = 19), normocytic (n = 14) and macrocytic (n = 11). An algorithm that included four levels of investigations was devised for each category.
RESULTS
After applying a systematic diagnostic approach, 33 patients (75 %) were diagnosed of whom 7 (15 %) had combined diagnoses, while 11 (25 %) patients remained undiagnosed. Based on the first, second, third and fourth levels of investigations, patients were diagnosed, respectively, as follows: of the 11 patients, 7 were microcytic, 3 normocytic and 1 macrocytic; of the 7 patients, 2 were microcytic, 2 normocytic, and 3 macrocytic; of 10 patients, 5 were microcytic, 4 normocytic and 1 macrocytic; finally, of the 16 patients, 8 were microcytic, 6 normocytic and 2 macrocytic. Numbers recorded appear higher than the actual number of the patients because some of them were diagnosed by more than one level of investigation. The diagnoses obtained in the microcytic group showed hemoglobinopathies, iron refractory iron deficiency anemia (IRIDA), membrane defects, sideroblastic anemia, hypo-transferrinemia, a combined diagnosis of sickle cell trait and pyropoikilocytosis. The diagnoses also showed a combined diagnosis of hereditary spherocytosis (HS) and alpha thalassemia minor, and a combined diagnosis of iron deficiency anemia and beta thalassemia minor, while 15 % remained undiagnosed. In the normocytic group, the diagnosis revealed autosomal recessive (AR) HS, vitamin B12 deficiency, pyruvate kinase deficiency (PKD), congenital dyserythropoietic anemia (CDA) type I, Diamond Blackfan anemia and beta thalassemia major. In addition, it showed a combined diagnosis of AR HS and CDA type II, a combined diagnosis of AR HS and PKD, and a combined diagnosis of dehydrated stomatocytosis (DHS) and G6PD carrier, meanwhile 20 % remained undiagnosed. Finally, the macrocytic group was diagnosed by vitamin B12 deficiency, sideroblastic anemia, PKD, a combined diagnosis of PKD and G6PD deficiency carrier, while 45 % remained undiagnosed.
CONCLUSION
Conducting a stepwise approach with different levels of investigations may help reach the diagnosis of difficult anemia without having to resort to unnecessary investigations. Combined diagnosis is an important cause of undiagnosed anemia, especially in countries with high frequency of consanguinity. The remaining 25 % of the patients continued to be undiagnosed, requiring more sophisticated investigations.
Topics: Adolescent; Humans; Child; Anemia, Iron-Deficiency; Anemia, Sideroblastic; beta-Thalassemia; Cross-Sectional Studies; Developing Countries; Vitamin B 12 Deficiency
PubMed: 37558589
DOI: 10.1016/j.bcmd.2023.102779 -
Blood Cells, Molecules & Diseases Nov 2023We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests...
Next generation sequencing (NGS) interest in deciphering erythrocyte molecular defects' association in red cell disorders: Clinical and erythrocyte phenotypes of patients with mutations inheritance in PIEZO1, Spectrin ß1, RhAG and SLC4A1.
We report here an instructive case referred at 16 months-old for exploration of hemolysis without anemia (compensated anemia with reticulocytosis). The biology tests confirmed the hemolysis with increased total and indirect bilirubin. The usual hemolysis diagnosis tests were normal (DAT, G6PD, PK, Hb electrophoresis) except cytology and ektacytometry suggesting an association of multiple red blood cell (RBC) membrane disorders. This led us to propose a molecular screening analysis using targeted-Next Generation Sequencing (t-NGS) with a capture technique on 93 genes involved in RBC and erythropoiesis defects. We identified 4 missense heterozygous allelic variations, all of them were described without any significance (VUS) in the SLC4A1, RhAG, PIEZO1 and SPTB genes. The study of the familial cosegregation and research functional tests allowed to decipher the role of at least two by two genes in the phenotype and the hemolytic disease of this young patient. Specialized t-NGS panel (or virtual exome/genome sequencing) in a disease-referent laboratory and the motivated collaboration of clinicians, biologists and scientists should be the gold standard for improving the diagnosis of the patients affected with RBC diseases or rare inherited anemias.
Topics: Humans; Spherocytosis, Hereditary; Spectrin; High-Throughput Nucleotide Sequencing; Hemolysis; Mutation; Erythrocytes; Hematologic Diseases; Phenotype; Anion Exchange Protein 1, Erythrocyte; Ion Channels
PubMed: 37516005
DOI: 10.1016/j.bcmd.2023.102780 -
Hematology (Amsterdam, Netherlands) Dec 2023Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which...
BACKGROUND
Severe autoimmune hemolytic anemia complicating hereditary spherocytosis is life threatening and has not been described in a case report. Here, we report a case in which this intractable disease was treated successfully with glucocorticoids and cyclosporine.
CASE PRESENTATION
A 25-year-old female patient with hereditary spherocytosis developed severe autoimmune hemolytic anemia after respiratory syncytial virus infection. Her hemoglobin level was 26 g/L and various anti-red blood cell antibodies were detected in her serum, making blood matching difficult. Glucocorticoid monotherapy was ineffective. With the addition of cyclosporine (50 mg/12 h), the patient's hemoglobin level increased significantly and the symptoms associated with anemia were greatly relieved.
CONCLUSION
In patients with severe autoimmune hemolytic anemia, especially when the presence of multiple anti-red blood cell antibodies and alloantibodies interferes with blood matching, a glucocorticoid-cyclosporine regimen may be tried.
Topics: Female; Humans; Adult; Anemia, Hemolytic, Autoimmune; Glucocorticoids; Cyclosporine; Spherocytosis, Hereditary; Hemoglobins; Anemia, Hemolytic
PubMed: 37504499
DOI: 10.1080/16078454.2023.2235832 -
Journal of Minimal Access Surgery Jan 2024A true left-sided gall bladder (LSG) is a rare finding, is mostly discovered incidentally and often presents with symptoms similar to those of a normally positioned gall...
A true left-sided gall bladder (LSG) is a rare finding, is mostly discovered incidentally and often presents with symptoms similar to those of a normally positioned gall bladder. The diagnosis in most cases is intraoperative. The surgical technique is frequently difficult, with an increased risk of intraoperative injuries and conversion to open surgery. In this case report, we describe a rare scenario of a young male with hereditary spherocytosis who presented with jaundice and splenomegaly. The diagnosis of LSG was made by chance during pre-operative imaging. The patient was successfully managed with a splenectomy and a cholecystectomy via the minimal access approach in the same setting.
PubMed: 37148108
DOI: 10.4103/jmas.jmas_347_22 -
Blood Advances Sep 2023Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism...
Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism behind this benefit remain largely overlooked. Here, we compared 7 nonsplenectomized and 13 splenectomized patients with mutations in the β-spectrin or the ankyrin gene. We showed that hematological parameters, spherocyte abundance, osmotic fragility, intracellular calcium, and extracellular vesicle release were largely but not completely restored by splenectomy, whereas cryohemolysis was not. Affected RBCs exhibited decreases in β-spectrin and/or ankyrin contents and slight alterations in spectrin membrane distribution, depending on the mutation. These modifications were found in both splenectomized and nonsplenectomized patients and poorly correlated with RBC functionality alteration, suggesting additional impairments. Accordingly, we found an increased abundance of septins, small guanosine triphosphate-binding cytoskeletal proteins. Septins-2, -7, and -8 but not -11 were less abundant upon splenectomy and correlated with the disease severity. Septin-2 membrane association was confirmed by immunolabeling. Except for cryohemolysis, all parameters of RBC morphology and functionality correlated with septin abundance. The increased septin content might result from RBC maturation defects, as evidenced by (1) the decreased protein 4.2 and Rh-associated glycoprotein content in all patient RBCs, (2) increased endoplasmic reticulum remnants and endocytosis proteins in nonsplenectomized patients, and (3) increased lysosomal and mitochondrial remnants in splenectomized patients. Our study paves the way for a better understanding of the involvement of septins in RBC membrane biophysical properties. In addition, the lack of restoration of septin-independent cryohemolysis by splenectomy may call into question its recommendation in specific cases.
Topics: Humans; Spectrin; Septins; Splenectomy; Ankyrins; Spherocytosis, Hereditary; Erythrocytes
PubMed: 36753606
DOI: 10.1182/bloodadvances.2022009114 -
Human Vaccines & Immunotherapeutics Dec 2023Herein, we report the case of a 22-year-old woman with hereditary spherocytosis (HS) whose condition worsened after administration of the coronavirus disease 2019...
Herein, we report the case of a 22-year-old woman with hereditary spherocytosis (HS) whose condition worsened after administration of the coronavirus disease 2019 (COVID-19), mRNA vaccine 'BNT162b2 Pfizer-BioNTech.' The woman had been diagnosed with HS in 2005, and her condition remained stable until February 2021. In March 2021, she received the first dose of the above vaccine and experienced pain at the injection site. After the second dose in April 2021, she developed fever and general malaise. Investigations revealed progression of hemolysis, which improved after a few days. To the best of our knowledge, this is the first report of progression of hemolysis in a patient with HS after administration of the mRNA vaccine COVID-19, BNT162b2 'Pfizer-BioNTech.'
Topics: Humans; Female; Young Adult; Adult; COVID-19 Vaccines; BNT162 Vaccine; Hemolysis; COVID-19; mRNA Vaccines
PubMed: 36625832
DOI: 10.1080/21645515.2023.2165381