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Journal of Hematopathology Jun 2023Hereditary spherocytosis (HS) is a common, hereditary hemolytic anemia (HHA) that is attributed to the disturbance of five erythrocyte membrane proteins. HS is also...
Hereditary spherocytosis (HS) is a common, hereditary hemolytic anemia (HHA) that is attributed to the disturbance of five erythrocyte membrane proteins. HS is also common in Guangxi, China. Target region capture high-throughput sequencing technology was used to analyze genetic mutations found in HS patients. Pedigree analysis was also performed, in some cases, to provide an optimized approach for the etiological diagnosis of complex, hereditary hemolytic anemia. Blood samples from the probands and their families were assessed by laboratory tests, target region capture high-throughput sequencing technology, and Sanger sequencing. We detected 79 HS patients from 37 unrelated families. The mutations observed in these patients were found mainly in four HS-related genes. These included SLC4A1, which was mutated in 31.65% of patients (25/79), SPTA1 (30.78% (24/79)), EPB42 (6.33% (5/79)), and SPTB (5.06% (4/79)). Composite genotype was observed in 26.58% (21/79) of patients and included mutations in two or more HS-related genes or mutations in HS-related genes combined with thalassemia or G6PD deficiency. No significant differences in clinical symptoms were found among patients of various genotypes except total bilirubin. Mean reticulocyte volume (MRV) and mean sphered cell volume (MSCV) of the composite genotype were significantly different from other groups. A total of 28 mutation types were found in HS-related genes. Using high-throughput sequencing technology, we also found some cases that had been misdiagnosed. MRV and MSCV are more significant in compound mutations as sensitive determinants of HS. High-throughput sequencing technology can be used to provide a more effective etiological diagnostic method for HS, with high efficiency and specificity.
Topics: Humans; China; Spherocytosis, Hereditary; Anemia, Hemolytic, Congenital; Genotype; Mutation
PubMed: 38175446
DOI: 10.1007/s12308-023-00545-8 -
Children (Basel, Switzerland) Nov 2023Same-day discharge after a cholecystectomy is a common practice in the adult population and has been demonstrated as safe and viable for children as well. However, there...
BACKGROUND
Same-day discharge after a cholecystectomy is a common practice in the adult population and has been demonstrated as safe and viable for children as well. However, there is a lack of comprehensive teaching models for pediatric cholecystectomy. Drawing inspiration from standardized outpatient procedures, this study aimed to assess the clinical outcomes and feasibility of teaching programs and an Enhanced Recovery After Surgery (ERAS) protocol following ambulatory laparoscopic cholecystectomy in pediatric patients.
METHODS
In 2015, an ERAS pathway for laparoscopic cholecystectomy (LC) was implemented, focusing on admission procedures, surgery timing, anesthetic choices, analgesia, postoperative feeding, mobilization, and pain assessment. Day-case surgery was not applicable for acute cholecystitis, choledochal lithiasis, sickle cell disease, and hereditary spherocytosis cases. The protocol was employed for a group of attending surgeons and fellows, as well as a group of residents under the supervision of experienced surgeons. A retrospective analysis was conducted to evaluate the feasibility and effectiveness of ambulatory cholecystectomy in children and its utilization in training pediatric surgical trainees.
RESULTS
Between 2015 and 2020, a total of 33 patients were included from a cohort of 162 children who underwent LC, with 15 children operated on by senior surgeons and 18 by young surgeons. The primary diagnoses were symptomatic gallbladder lithiasis ( = 32) and biliary dyskinesia ( = 1). The median age at the time of surgery was 11.3 years (interquartile range (IQR) 4.9-18), and the median duration of surgery was 54 min (IQR 13-145). One intraoperative complication occurred, involving gallbladder rupture and the dissemination of lithiasis into the peritoneal cavity. Three patients (9%) required an overnight stay, while no postoperative complications or readmissions within 30 days were observed. ERAS was successfully implemented in 30 patients (91%). No significant differences in surgical outcomes were noted between senior and young surgeons. At an average follow-up of 55 months, no long-term sequelae were identified.
CONCLUSIONS
These findings align with the current trend of increasing use of outpatient laparoscopic cholecystectomy and underscore its feasibility in the pediatric population. The application of a structured ERAS protocol appears viable and practical for training the next generation of pediatric surgeons.
LEVEL OF EVIDENCE
Level III.
PubMed: 38136083
DOI: 10.3390/children10121881 -
Frontiers in Genetics 2023Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the...
Hereditary spherocytosis (HS) is a congenital haemolytic anaemia attributed to dysregulation or abnormal quantities of erythrocyte membrane proteins. Currently, the most common erythrocytic gene, spectrin β (), variants are located in exons and give rise to mRNA defects. However, the genetic characteristics and pathogenic mechanisms of intronic variants are not completely understood. This study aimed to analyse a rare intronic inversion variant in the gene associated with HS, and explore the impact of the variant on mRNA splicing. The clinical manifestations of the patient were summarised and analysed for spherocytosis phenotype diagnosis. The pathogenic variant was identified in the proband using targeted next-generation and Sanger sequencing. RNA sequencing was performed to analyse whether gene splicing and expression were affected. Targeted next-generation sequencing identified a novel disease-associated intronic inversion variant of the gene in the proband. The inversion variant was located between intron 19 and 20, and contained the entire exon 20 and partial sequences of adjacent introns. Sanger sequencing confirmed that the intronic inversion variant only appeared in the genome of the proband, not in his parents. RNA sequencing revealed that the variant could result in the skipping of exon 20 and reduced expression of mRNA. This study identifies a rare intronic inversion variant in the gene associated with hereditary spherocytosis. The pathogenic variant can lead to exon 20 skipping and decreased gene expression. This finding has not been previously reported in any literature. This study can expand the intronic variant spectrum of the gene, deepen our understanding of HS pathogenesis, and contribute to the genetic diagnosis and clinical management of patients.
PubMed: 38111681
DOI: 10.3389/fgene.2023.1309040 -
Applied Bionics and Biomechanics 2023[This retracts the article DOI: 10.1155/2022/6228965.].
[This retracts the article DOI: 10.1155/2022/6228965.].
PubMed: 38075143
DOI: 10.1155/2023/9846792 -
International Journal of Molecular... Nov 2023Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS),...
Congenital defects of the erythrocyte membrane are common in northern Europe and all over the world. The resulting diseases, for example, hereditary spherocytosis (HS), are often underdiagnosed, partly due to their sometimes mild and asymptomatic courses. In addition to a broad clinical spectrum, this is also due to the occasionally complex diagnostics that are not available to every patient. To test whether next-generation sequencing (NGS) could replace time-consuming spherocytosis-specific functional tests, 22 consecutive patients with suspected red cell membranopathy underwent functional blood tests. We were able to identify the causative genetic defect in all patients with suspected HS who underwent genetic testing ( = 17). The sensitivity of the NGS approach, which tests five genes ( (gene product: ankyrin1), (erythrocyte membrane protein band4.2), (band3), (α-spectrin), and (β-spectrin)), was 100% (95% confidence interval: 81.5-100.0%). The major advantage of genetic testing in the paediatric setting is the small amount of blood required (<200 µL), and compared to functional assays, sample stability is not an issue. The combination of medical history, basic laboratory parameters, and an NGS panel with five genes is sufficient for diagnosis in most cases. Only in rare cases, a more comprehensive functional screening is required.
Topics: Humans; Child; Ankyrins; Mutation; Spherocytosis, Hereditary; Spectrin; Cytoskeletal Proteins; High-Throughput Nucleotide Sequencing
PubMed: 38069343
DOI: 10.3390/ijms242317021 -
Annales de Biologie Clinique Nov 2023The discovery of hemolytic anemia requires a meticulous investigation to determine its etiology. Among patients of African origin, it is not uncommon to find multiple...
The discovery of hemolytic anemia requires a meticulous investigation to determine its etiology. Among patients of African origin, it is not uncommon to find multiple constitutional red blood cell abnormalities, which can complicate diagnosis. We herein describe the case of a two-year-old child presenting with acute hemolytic anemia. A G6PD deficiency, hereditary spherocytosis, and a sickle cell trait A/S were simultaneously identified, all within the context of a primary infection with Parvovirus B19. This virus commonly triggers acute anemia in children exhibiting constitutional red blood cell abnormalities and need to be considered in such cases.
PubMed: 38018827
DOI: 10.1684/abc.2023.1843 -
Annals of Hematology Feb 2024Red blood cell (RBC) membrane disorders represent a significant category of hereditary hemolytic anemia; however, information from Southeast Asia is limited. We...
Red blood cell (RBC) membrane disorders represent a significant category of hereditary hemolytic anemia; however, information from Southeast Asia is limited. We established a national registry aiming to characterize RBC membrane disorders and their molecular features in Thailand. A total of 100 patients (99 kindreds) diagnosed with RBC membrane disorders between 2011 and 2020 from seven university hospitals were enrolled. The most prevalent disorders observed were hereditary elliptocytosis (HE; n=33), hereditary pyropoikilocytosis (HPP; n=28), hereditary spherocytosis (HS; n=19), Southeast Asian ovalocytosis (SAO; n=10 of 9 kindreds), and two cases of homozygous SAO. The remaining cases were grouped as unclassified membrane disorder. Seventy-six patients (76%) were molecularly confirmed by PCR, direct DNA sequencing, or hi-throughput sequencing. The primary causative gene for HE and HPP was SPTB, accounting for 28 out of 29 studied alleles for HE and 56 of 56 studied alleles for HPP. In the case of HS, dominant sporadic mutations in the ANK1 gene (n=4) and SPTB gene (n=3) were identified as the underlying cause. Notably, the four most common variants causing HE and HPP were SPTB Providence (c.6055 T>C), SPTB Buffalo (c.6074 T>G), SPTB Chiang Mai (c.6224 A>G), and SPTB c.6171__82delins TGCCCAGCT. These recurrent SPTB mutations accounted for 79 out of 84 mutated SPTB alleles (94%). In summary, HE and hereditary HPP associated with recurrent SPTB mutations are the predominant types of RBC membrane disorders observed in Thailand. These findings have significant implications for the clinical management and future research of RBC membrane disorders in the region.
Topics: Humans; Elliptocytosis, Hereditary; Erythrocyte Membrane; Mutation; Spherocytosis, Hereditary; Thailand; Multicenter Studies as Topic; Registries
PubMed: 37996759
DOI: 10.1007/s00277-023-05555-1 -
Human Vaccines & Immunotherapeutics Dec 2023
Topics: Humans; COVID-19; COVID-19 Vaccines; Hemolysis; Spherocytosis, Hereditary; mRNA Vaccines
PubMed: 37992397
DOI: 10.1080/21645515.2023.2286117 -
Simultaneous Robotic-Assisted Splenectomy and Cholecystectomy in Children: Is It Safe and Effective?Journal of Laparoendoscopic & Advanced... May 2024Hematologic conditions such as hereditary spherocytosis, sickle cell disease, and idiopathic thrombocytopenic purpura are frequently linked to cholelithiasis. In...
Hematologic conditions such as hereditary spherocytosis, sickle cell disease, and idiopathic thrombocytopenic purpura are frequently linked to cholelithiasis. In instances where symptoms are present, simultaneous cholecystectomy and splenectomy are commonly recommended. Our aim was to assess the outcomes of robotic-assisted procedures conducted for simultaneous surgical issues involving the spleen and gallbladder in pediatric patients. We have made a simultaneous retrospective study of children with hereditary hematological diseases who underwent combined robotic-assisted splenectomy and cholecystectomy at our institution from January 2010 to December 2021. Demographics, clinical features, intraoperative data, length of hospital stay, postoperative complications, and follow-up outcomes were analyzed. A total of 11 patients (6 male; 5 female) were included, with a mean age of 13.9 ± 4.4 years (range 8-17). Hereditary spherocytosis was the most common disease (7 cases), followed by sick cell disease (4 cases), with associated symptomatic gallbladder litiasis in all of them. Both operations were carried out using the da Vinci Surgical Si System in a single docking robotic platform (four robotic arms). Median total surgery time was 145 minutes (Q1-Q3: 115-162). Minimal intraoperative bleeding was recorded (mean 45 ± 15 mL), with no intraoperative complications or conversion. Median length of hospital stay was 3 days (Q1-Q3: 2-4). There were no cases of surgical wound infections or postoperative bleeding documented. Simultaneous robotic-assisted splenectomy and cholecystectomy can be considered safe and feasible interventions in children with hematological diseases that affect both the spleen and the gallbladder. However, further research is needed to enhance the existing evidence and establish a standardized approach.
Topics: Humans; Female; Male; Splenectomy; Child; Retrospective Studies; Robotic Surgical Procedures; Adolescent; Length of Stay; Cholecystectomy; Postoperative Complications; Treatment Outcome; Operative Time; Cholelithiasis
PubMed: 37976218
DOI: 10.1089/lap.2023.0255 -
Blood Cells, Molecules & Diseases Jan 2024Several syndromes affecting the red cell that mimic those induced by germline mutations may result from a somatic mutation that accompanies a myeloid malignancy. These... (Review)
Review
Several syndromes affecting the red cell that mimic those induced by germline mutations may result from a somatic mutation that accompanies a myeloid malignancy. These syndromes are most notable in cases of myelodysplastic syndrome, but they are not limited to any one category of myeloid neoplasm. Their occurrence in males exceed the male predominance that is evident in myeloid neoplasms. The syndromes include disorders of globin chain synthesis (α- and β-thalassemia), heme synthesis (erythropoietic porphyria and erythropoietic uroporphyria), red cell membrane structure (elliptocytosis and spherocytosis), red cell enzyme activity (pyruvate kinase deficiency, glucose-6-phosphate dehydrogenase deficiency) and lowered expression of red cell ABO blood group antigens. This historical review describes the path to uncovering these acquired syndromes and their causal somatic mutations, where known. These syndromes often go unrecognized because of the dominant concern of the primary neoplasm. They may add to the healthcare needs of the patient.
Topics: Humans; Male; Female; Clonal Hematopoiesis; Erythrocytes; Anemia, Hemolytic, Congenital Nonspherocytic; Myelodysplastic Syndromes; Neoplasms; Mutation; Hematopoiesis
PubMed: 37951089
DOI: 10.1016/j.bcmd.2023.102801