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IDCases 2023
PubMed: 37434610
DOI: 10.1016/j.idcr.2023.e01820 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Apr 2023Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the...
OBJECTIVES
Hereditary spherocytosis (HS) is the most common hereditary defect of the red cell membrane, mainly characterized by anemia, jaundice, and splenomegaly. Due to the atypical clinical manifestations and negative family history of some patients, as well as the low sensitivity and specificity of traditional laboratory examinations, it is easy for it to escape diagnosis or be misdiagnosed. At present, it has been confirmed that the mutation of , , , and genes can cause the deletion of their corresponding coding proteins, and thus lead to the defect of erythrocyte membrane. This study aims to analyze the feasibility and clinical application value of HS gene diagnosis.
METHODS
Data of 26 patients from Hunan, China with HS admitted to the Department of Hematology, Second Xiangya Hospital of Central South University from January 2018 to September 2021 were retrospectively collected, and their clinical manifestations and results of laboratory examinations were analyzed. Next-generation sequencing (NGS) combined with Sanger sequencing were applied. The mutation of HS pathogenic gene and the variation of uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1 (), a key enzyme in the regulation of bilirubin metabolism, were detected. The results of pathogenic gene variations were interpreted pathogenic gene variations in accordance with published by the American College of Medical Genetics and Genomics (ACMG). The clinical characteristics of patients with different gene variants were analyzed, and the clinical diagnosis and genetic diagnosis were compared.
RESULTS
Among the 26 patients with HS, there were 23 cases of anemia, 25 cases of jaundice, 24 cases of splenomegaly, and 14 cases of cholelithiasis. There were 16 cases with family history and 10 cases without family history. The results of HS mutation test were positive in 25 cases and negative in 1 case. A total of 18 heterozygous mutations of HS pathogenic genes were detected in 19 families, among which 14 were pathogenic, 1 was likely pathogenic and 3 were of unknown significance. mutations (12) and mutations (4) were the most common. The main variation types were nonsense mutation (9). There were no significant differences in peripheral blood cell parameters and hemolysis indicators between the mutant group and the mutant group (all >0.05). The rate of splenectomy in mutation group was higher than that in mutation group, and the difference was statistically significant (χ=6.970, =0.014). There were no significant differences in peripheral blood cell parameters and hemolysis indicators among different mutation types (nonsense mutation, frameshift mutation, splice site mutation and missense mutation) (all >0.05). Among the 18 clinically confirmedpatients, there were 17 cases whose diagnosis is consistent with the genetic diagnosis. Eight patients were clinically suspected, and all of them were confirmed by detection of HS gene mutation. Twenty-four patients with HS underwent mutation detection, among which 5 patients carried mutation resulting in a decrease in enzyme activity, and 19 patients had normal enzyme activity. The level of total bilirubin (TBIL) in the group with reduced enzyme activity was higher than that in the group with normal enzyme activity, and the difference was statistically significant (U=22, =0.038).
CONCLUSIONS
Most patients with HS have anemia, jaundice and splenomegaly, often accompanied by cholelithiasis. and mutations are the most common mutations in HS pathogenic genes among patients in Hunan, China, and there was no significant correlation between genotype and clinical phenotype. Genetic diagnosis is highly consistent with clinical diagnosis. The decrease of UGT1A1 enzyme activity can lead to the aggravation of jaundice in HS patients. Clinical combined gene diagnosis is beneficial for the rapid and precision diagnosis of HS. The detection of UGT1A1 enzyme activity related gene variation plays an important role in evaluation of HS jaundice.
Topics: Humans; Codon, Nonsense; Hemolysis; Retrospective Studies; Splenomegaly; Bilirubin
PubMed: 37385619
DOI: 10.11817/j.issn.1672-7347.2023.220390 -
Zhonghua Xue Ye Xue Za Zhi = Zhonghua... Apr 2023To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. The clinical and gene... (Review)
Review
To report gene mutations in nine patients with hereditary elliptocytosis (HE) and analyze the characteristics of pathogenic gene mutations in HE. The clinical and gene mutations of nine patients clinically diagnosed with HE at Institute of Hematology & Blood Diseases Hospital from June 2018 to February 2022 were reported and verified by next-generation sequencing to analyze the relationship between gene mutations and clinical phenotypes. Erythrocyte membrane protein gene mutations were detected among nine patients with HE, including six with SPTA1 mutation, one with SPTB mutation, one with EPB41 mutation, and one with chromosome 20 copy deletion. A total of 11 gene mutation sites were involved, including 6 known mutations and 5 novel mutations. The five novel mutations included SPTA1: c.1247A>C (p. K416T) in exon 9, c.1891delG (p. A631fs*17) in exon 15, E6-E12 Del; SPTB: c.154C>T (p. R52W) ; and EPB41: c.1636A>G (p. I546V) . Three of the six patients with the SPTA1 mutation were SPTA1 exon 9 mutation. SPTA1 is the most common mutant gene in patients with HE.
Topics: Humans; Mutation; Elliptocytosis, Hereditary; Erythrocyte Membrane; Exons; High-Throughput Nucleotide Sequencing; Spherocytosis, Hereditary
PubMed: 37357001
DOI: 10.3760/cma.j.issn.0253-2727.2023.04.009 -
Cureus May 2023Accessory spleen and splenosis are two types of ectopic spleen. An accessory spleen can be found in various sites in the abdomen, but an intrahepatic accessory spleen is...
Accessory spleen and splenosis are two types of ectopic spleen. An accessory spleen can be found in various sites in the abdomen, but an intrahepatic accessory spleen is very rare though many case reports of intrahepatic splenosis are available. This case report presents the incidental diagnosis of accessory spleen in the liver of a 57-year-old male while undergoing laparoscopic diaphragmatic repair. The patient had a history of splenectomy 27 years ago for hereditary spherocytosis, but his routine haemogram did not show any features of the ectopic splenic function. Intraoperatively, a mass was suspected in the liver and was resected. Histopathology revealed an accessory spleen with well-preserved red and white pulp architecture. Though a history of splenectomy suggested a diagnosis of splenosis, a well-encapsulated and preserved splenic architecture confirmed the diagnosis of accessory spleen. Accessory spleen or splenosis can be diagnosed radiologically using Tc-99m-labeled heat-denatured red blood cells (HRBC) and Tc-99m sulfur colloid scans, but the gold standard is histopathological examination. Ectopic spleen is mostly asymptomatic but usually results in unnecessary surgeries as it is difficult to differentiate from benign or malignant tumors. Thus, a high degree of suspicion and awareness is necessary for early and prompt diagnosis.
PubMed: 37332428
DOI: 10.7759/cureus.39185 -
Journal of Investigative Medicine High... 2023This case report describes a novel mutation of the gene as a potential pathogenic cause of spherocytosis. A 3-week-old male presented with clinical and laboratory signs...
This case report describes a novel mutation of the gene as a potential pathogenic cause of spherocytosis. A 3-week-old male presented with clinical and laboratory signs consistent with hemolytic spherocytosis, including jaundice, hyperbilirubinemia, anemia, reticulocytosis, negative Coombs test, no ABO or Rh incompatibility, and a peripheral blood smear notable for numerous spherocytes. His laboratory work demonstrated persistent anemia despite daily folate prompting next-generation sequencing which revealed a novel mutation in the gene resulting in a nonfunctioning protein product. Correlation of the genetic finding with clinical presentation may help guide management for this and future patients.
Topics: Infant, Newborn; Humans; Male; Heterozygote; High-Throughput Nucleotide Sequencing; Hyperbilirubinemia; Mutation
PubMed: 37306287
DOI: 10.1177/23247096231180552 -
BioRxiv : the Preprint Server For... May 2023Red blood cell (RBC) disorders affect billions worldwide. While alterations in the physical properties of aberrant RBCs and associated hemodynamic changes are readily...
Red blood cell (RBC) disorders affect billions worldwide. While alterations in the physical properties of aberrant RBCs and associated hemodynamic changes are readily observed, in conditions such as sickle cell disease and iron deficiency, RBC disorders can also be associated with vascular dysfunction. The mechanisms of vasculopathy in those diseases remain unclear and scant research has explored whether biophysical alterations of RBCs can directly affect vascular function. Here we hypothesize that the purely physical interactions between aberrant RBCs and endothelial cells, due to the margination of stiff aberrant RBCs, play a key role in this phenomenon for a range of disorders. This hypothesis is tested by direct simulations of a cellular scale computational model of blood flow in sickle cell disease, iron deficiency anemia, COVID-19, and spherocytosis. We characterize cell distributions for normal and aberrant RBC mixtures in straight and curved tubes, the latter to address issues of geometric complexity that arise in the microcirculation. In all cases aberrant RBCs strongly localize near the vessel walls (margination) due to contrasts in cell size, shape, and deformability from the normal cells. In the curved channel, the distribution of marginated cells is very heterogeneous, indicating a key role for vascular geometry. Finally, we characterize the shear stresses on the vessel walls; consistent with our hypothesis, the marginated aberrant cells generate large transient stress fluctuations due to the high velocity gradients induced by their near-wall motions. The anomalous stress fluctuations experienced by endothelial cells may be responsible for the observed vascular inflammation.
PubMed: 37293094
DOI: 10.1101/2023.05.16.541016 -
BMC Genomics Jun 2023Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood...
BACKGROUND
Hereditary spherocytosis (HS) is a common inherited hemolytic anemia, caused by mutations in five genes that encode erythrocyte membrane skeleton proteins. The red blood cell (RBC) lifespan could directly reflect the degree of hemolysis. In the present cohort of 23 patients with HS, we performed next-generation sequencing (NGS) and Levitt's carbon monoxide (CO) breath test to investigate the potential genotype-degree of hemolysis correlation.
RESULTS
In the present cohort, we identified 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in 23 patients with HS, and the median RBC lifespan was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13 (8-23), 13 (8-48) and 14 (12-39) days, respectively, with no statistically significant difference (P = 0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13 (8-20) days, respectively, with no significant difference (P = 0.514). Similarly, we found no significant difference in the RBC lifespan of patients with mutations located in the spectrin-binding domain and the nonspectrin-binding domain [14 (8-18) vs. 12.5 (8-48) days, P = 0.959]. In terms of the composition of mutated genes, 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations, while 75% of patients with mild hemolysis carried SPTB or SLC4A1 mutations. In contrast, 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% of patients with severe hemolysis had SPTB or SLC4A1 mutations. However, there was no statistically significant difference in the distribution of mutated genes between the two groups (P = 0.400).
CONCLUSION
The present study is the first to investigate the potential association between genotype and degree of hemolysis in HS. The present findings indicated that there is no significant correlation between genotype and degree of hemolysis in HS.
Topics: Humans; Hemolysis; Ankyrins; Spectrin; Spherocytosis, Hereditary; Cytoskeletal Proteins; Membrane Proteins; Mutation; Genotype
PubMed: 37280519
DOI: 10.1186/s12864-023-09364-8 -
BMC Pediatrics May 2023Due to the heterogeneity of the phenotype of Hereditary spherocytosis (HS) patients, some patients may have rare clinical complications such as biliary obstruction and...
BACKGROUND
Due to the heterogeneity of the phenotype of Hereditary spherocytosis (HS) patients, some patients may have rare clinical complications such as biliary obstruction and ultra-high bilirubinemia.
CASE PRESENTATION
A 8-y-old boy presented to the emergency with complaints of anemia for 6 years and worsened abdominal pain and scleral yellowing of the skin for 2 days. Physical examination showed tenderness in the middle and upper abdomen and splenomegaly. Abdominal CT revealed biliary obstruction. Genetic analysis revealed a de novo mutation in the gene ANK1, HS with biliary obstruction was diagnosed. The surgery of bile duct exploration and T-tube drainage, and splenectomy were performed successively. This patient was followed up for 13 months after splenectomy, and his condition was stable.
CONCLUSION
The diagnosis of HS is not clinically difficult, and once a patient with HS is diagnosed, regular follow-up management and standardized treatment are required. Genetic testing is also needed to screen for other genetic disorders that may co-exist in patients with HS who do not have a good efficacy or who have a long-term chronic onset of jaundice.
Topics: Humans; Child; Mutation; Ankyrins; Spherocytosis, Hereditary; Phenotype; Cholestasis
PubMed: 37246216
DOI: 10.1186/s12887-023-04092-0 -
Viruses May 2023Parvovirus B19 (B19V) infection varies clinically depending on the host's immune status. Due to red blood cell precursors tropism, B19V can cause chronic anemia and...
Parvovirus B19 (B19V) infection varies clinically depending on the host's immune status. Due to red blood cell precursors tropism, B19V can cause chronic anemia and transient aplastic crisis in patients with immunosuppression or chronic hemolysis. We report three rare cases of Brazilian adults living with human immunodeficiency virus (HIV) with B19V infection. All cases presented severe anemia and required red blood cell transfusions. The first patient had low CD4 counts and was treated with intravenous immunoglobulin (IVIG). As he remained poorly adherent to antiretroviral therapy (ART), B19V detection persisted. The second patient had sudden pancytopenia despite being on ART with an undetectable HIV viral load. He had historically low CD4 counts, fully responded to IVIG, and had undiagnosed hereditary spherocytosis. The third individual was recently diagnosed with HIV and tuberculosis (TB). One month after ART initiation, he was hospitalized with anemia aggravation and cholestatic hepatitis. An analysis of his serum revealed B19V DNA and anti-B19V IgG, corroborating bone marrow findings and a persistent B19V infection. The symptoms resolved and B19V became undetectable. In all cases, real time PCR was essential for diagnosing B19V. Our findings showed that adherence to ART was crucial to B19V clearance in HIV-patients and highlighted the importance of the early recognition of B19V disease in unexplained cytopenias.
Topics: Male; Humans; Adult; Erythema Infectiosum; HIV; Acquired Immunodeficiency Syndrome; Immunoglobulins, Intravenous; Parvoviridae Infections; Anemia; Parvovirus B19, Human; HIV Infections; DNA, Viral
PubMed: 37243210
DOI: 10.3390/v15051124