Search

Objective: To explore the comparative postoperative efficacy of partial splenectomy (PS) and total splenectomy (TS) in the treatment of children with hereditary spherocytosis (HS). Methods: The relevant HS studies from databases were searched and screened, comparing the differences in hemoglobin concentration, reticulocyte percentage, bilirubin concentration before and after TS and PS surgery, and during the follow-up period, as well as the incidence of postoperative adverse events. Statistical analysis was performed using Review Manager 5.4. Results: A total of 5 studies were included in this meta-analysis, with a cumulative enrollment of 312 children, 130 in the PS group and 182 in the TS group. The meta-analysis results showed that both PS and TS groups had statistically significant differences in postoperative hematological outcomes compared to before surgery, with TS showing better improvement than PS. In the postoperative follow-up, the changes in hematological outcomes between PS and TS were statistically significant for hemoglobin concentration: within 1 year [MD = 1.85, 95%CI(1.09,2.60)], 1–2 years [MD = 1.74, 95%CI(0.25,3.24)], not statistically significant for 4–6 years [MD = 1.28, 95%CI(-1.75,4.32)]; for reticulocyte percentage: within 1 year [MD = 2.23, 95%CI(0.80,3.66)] was statistically significant, not statistically significant for 4–6 years [MD = 1.77, 95%CI(-2.04,5.59)]; for serum bilirubin concentration: within 1 year [MD = 1.55, 95%CI(0.91,2.18)] was statistically significant, not statistically significant for 1–2 years [MD = 1.77, 95%CI(-2.04,5.99)]. In the incidence of postoperative adverse events, the incidence of cholelithiasis [MD = 1.77, 95%CI(-2.04,5.99)] showed a statistically significant difference between PS and TS, while there were no statistically significant differences in other included events, such as postoperative infection rate, secondary surgery rate, thrombosis rate, postoperative hemorrhage rate, and transfusion therapy rate. Conclusion: Splenectomy is a beneficial surgical strategy for children with moderate-to-severe HS, reducing; early hematological outcomes of TS are more robust than PS in the follow-up period, and there is no difference between the two in the later period; for postoperative adverse events, the incidence of cholelithiasis in children after PS is higher than after TS, and there is a risk of requiring a second surgery for total splenectomy due to hemolytic recurrences. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis (HS) is the most common hereditary hemolytic disease with defects in red blood cells (RBC) membrane proteins caused by mutations in membrane protein genes, like SPTB, SPTA1 and ANK1. Gilbert syndrome (GS) is a disease characterized by a mild deficiency of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity and unconjugated hyperbilirubinemia, largely caused by UGT1A1 mutations. The two inherited diseases HS and GS are rarely occurred in the same patient and are easy to be misdiagnosed, resulting in excessive diagnosis and treatment. Here, we report a rare case of HS combined with GS due to mutations in the SPTB and UGT1A1 genes. A 50-year-old man who had an over 40-year history of jaundice was admitted to our hospital owing to fatigue and fever. His blood analysis showed low hemoglobin (74 g/L), high reticulocyte (23.5%) and high serum bilirubin (65 μmol/L); abdominal ultrasound revealed calculous cholecystitis and splenomegaly. Considering a possible diagnosis of hemolytic anemia, further examinations showed 42% spherocytes in blood smears and high erythroid lineage hyperplasia in bone marrow. Subsequently, 151 jaundice-related genes panel sequencing was done and results showed SPTB p.N1260fs and UGT1A1 p.G71R mutations. Then the patient was diagnosed with HS complicated with GS. Anti-infection and supportive treatments were providing to the patient, while infection removed, the hemoglobin recovered to normal, and no additional treatment was given. These findings of this report indicate that patients who are considered hemolytic anemia presenting with jaundice and anemia, genetic testing is a crucial method for the final diagnosis and bilirubin metabolic disease should also be concerned. [ABSTRACT FROM AUTHOR]

Background: Heterozygous pathogenic variants of SPTB cause hereditary spherocytosis (HS) in a quarter of cases. Case report: A 14-day-old male presenting with persistent anemia and hyperbilirubinemia was diagnosed with HS by increased red blood cell osmotic fragility and decreased fluorescence on the eosin-5′-maleimide binding test. For his failure to thrive and hypotonia, genetic sequencing revealed a de novo variant of the SPTB gene (p.Q1034X) on exon 15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. A variant of uncertain significance (p.R438W) in the chondroitin sulfate synthase 1 (CHSY1) gene was incidentally found. Loss of CHSY1 is associated with autosomal recessive Temtamy preaxial brachydactyly syndrome (TPBS). However, this patient's heterozygosity and lack of typical TPBS phenotype make this variant less likely the cause of his symptoms. Conclusion: Further investigation can evaluate a potential link between the patient's presentation and these gene variants.

Abstract Background Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant’s pathogenicity and reveal a patient’s genetic etiology. Methods The clinical data of a patient with HS who underwent genetic sequencing at the Children’s Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. Results A novel variant (c.301–2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301–2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. Conclusion We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis.

Abstract Objective This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS). Methods Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (

A congenital protein anomaly in the erythrocyte membrane skeleton causes a hereditary haemolytic illness known as hereditary spherocytosis (HS). The primary characteristic of HS is an increase in the number of tiny spherical red blood cells in the peripheral blood. The chief clinical features of HS include anaemia, jaundice, splenomegaly, spherical erythrocytosis in the blood, chronic anaemia with haemolysis, and recurrent acute attacks. Most patients have a family history; some have autosomal recessive inheritance, whereas most have autosomal dominant inheritance. In cases of severe hyperbilirubinemia disproportionate to haemolysis, other causes of hyperbilirubinemia should be considered. Gilbert syndrome (GS) is an autosomal dominant illness caused by the reduced activity of uridine diphosphate-glucuronosyl transferase lAl and is characterised by intermittent hyperbilirubinemia without any other signs or symptoms of liver disease. The possibility of the coexistence of HS and GS is very limited. Here we present the case of an elderly man with yellow skin and sclera recurring anaemia, and a final diagnosis of coexisting HS and GS.

Abstract Background Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications resulting from hemolysis. Despite being the most prevalent cause of hereditary chronic hemolysis, the standards of surgical management are based solely on expert opinion. Objective We analyze the risk of hemolysis in HS patients after cardiac surgery based on a systematic review of the literature. We also describe a case of a patient with hereditary spherocytosis who underwent aortic valve repair. Methods This systematic review was registered in the PROSPERO international prospective register of systematic reviews (CRD42023417666) and included records from Embase, MEDLINE, Web of Science, and Google Scholar databases. The case study investigates a 38-year-old patient who underwent surgery for an aortic valve defect in mid-2022. Results Of the 787 search results, 21 studies describing 23 cases of HS undergoing cardiac surgery were included in the final analysis. Hemolysis was diagnosed in five patients (one coronary artery bypass graft surgery, two aortic valve bioprosthesis, one ventricular septal defect closure, and one mitral valve plasty). None of the patients died in the perioperative period. Also, no significant clinical hemolysis was observed in our patient during the perioperative period. Conclusions The literature data show that hemolysis is not common in patients with HS undergoing various cardiac surgery techniques. The typical management of a patient with mild/moderate HS does not appear to increase the risk of significant clinical hemolysis. Commonly accepted beliefs about factors inducing hemolysis during cardiac surgery may not be fully justified and require further investigation.

Background: Hereditary spherocytosis (HS, MIM#612641) is one of the most common hereditary hemolytic disorders. This study aimed to confirm a novel variant's pathogenicity and reveal a patient's genetic etiology. Methods: The clinical data of a patient with HS who underwent genetic sequencing at the Children's Hospital of Chongqing Medical University were reviewed retrospectively. In silico prediction and in vitro minigene splicing reporter system were then conducted on the detected variant to analyze its intramolecular impact. A summary of the literature related to HS due to SPTB gene variants was also presented. Results: A novel variant (c.301–2 A > G) in the SPTB gene (NM_001024858.4) was identified in the proband. Using Sanger sequencing, we conclusively confirmed that the inheritance of the variant could not be traced to the biological parents. The in vitro minigene assay revealed three different transcripts derived from the c.301–2 A > G variant: r.301_474del, r.301_306delCCAAAG, and r.301-1_301-57ins. Through a literature review, patients with HS who had been genotypically validated were summarized and the SPTB gene variant profile was mapped. Conclusion: We identified a splicing variant of the SPTB gene, thus confirming its aberrant translation. The novel variant was the probable genetic etiology of the proband with HS. Our findings expanded the variant spectrum of the SPTB gene, thus improving the understanding of the associated hereditary hemolytic disorders from a clinical and molecular perspective and contributing to the foundation of genetic counseling and diagnosis. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS). Methods: Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years). Results: A total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences. Conclusion: This study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis (HS) is a membranopathy that impacts the vertical junctions between the cytoskeleton and the plasma membrane of erythrocytes. The gold standard method for diagnosing it is osmotic gradient ektacytometry (OGE). However, access to this technique is scarce. We have devised a straightforward approach utilizing flow cytometry to quantify variations in an osmotic gradient, relying on FSC-H/SSC-H patterns. We studied 14 patients (9 pediatric, 5 adults) and 54 healthy controls (16 pediatric, 38 adults). After assessing the behavior of the samples in several osmolar gradients we selected for the study the 176, 308, and 458 mOsm/kg levels as hypo-osmolar, iso-osmolar, and hyper-osmolar references. We then selected the iso-osmolar point for assessment to determine its efficacy in discriminating between patient and control groups using a receiver operating characteristic curve. In the pediatric group, the area under the curve (AUC) was 1.0, indicating 100% sensitivity and 93.3% specificity. Conversely, in the adult group, the AUC was 0.98, with 80% sensitivity and 90.9% specificity. We introduce a method that is easily replicable and demonstrates high sensitivity and specificity. This technique could prove valuable in the diagnosis of spherocytosis. [ABSTRACT FROM AUTHOR]

Background: Due to the distinctive nature of cardiac surgery, patients suffering from hereditary spherocytosis (HS) are potentially at a high risk of perioperative complications resulting from hemolysis. Despite being the most prevalent cause of hereditary chronic hemolysis, the standards of surgical management are based solely on expert opinion. Objective: We analyze the risk of hemolysis in HS patients after cardiac surgery based on a systematic review of the literature. We also describe a case of a patient with hereditary spherocytosis who underwent aortic valve repair. Methods: This systematic review was registered in the PROSPERO international prospective register of systematic reviews (CRD42023417666) and included records from Embase, MEDLINE, Web of Science, and Google Scholar databases. The case study investigates a 38-year-old patient who underwent surgery for an aortic valve defect in mid-2022. Results: Of the 787 search results, 21 studies describing 23 cases of HS undergoing cardiac surgery were included in the final analysis. Hemolysis was diagnosed in five patients (one coronary artery bypass graft surgery, two aortic valve bioprosthesis, one ventricular septal defect closure, and one mitral valve plasty). None of the patients died in the perioperative period. Also, no significant clinical hemolysis was observed in our patient during the perioperative period. Conclusions: The literature data show that hemolysis is not common in patients with HS undergoing various cardiac surgery techniques. The typical management of a patient with mild/moderate HS does not appear to increase the risk of significant clinical hemolysis. Commonly accepted beliefs about factors inducing hemolysis during cardiac surgery may not be fully justified and require further investigation. [ABSTRACT FROM AUTHOR]

Key Clinical Message: When a person has both HS and beta‐thalassemia, their clinical symptoms tend to be less severe. This is because these two conditions have contrasting features. If the clinical symptoms and laboratory results cannot be solely attributed to hemolytic anemia, it is important to consider the possibility of another form of hemolytic anemia coexisting. We present a 26‐year‐old woman who has been experiencing abdominal pain, jaundice, and anemia for the past 15 years. Initially, she was diagnosed with gallstones and splenomegaly, but after a thorough hematology examination conducted by expert colleagues, it was discovered that she had both beta‐thalassemia and hereditary spherocytosis. The osmotic fragility test confirmed this diagnosis. The patient was advised to undergo both splenectomy and cholecystectomy procedures. It is worth noting that the co‐occurrence of these two conditions is rare. [ABSTRACT FROM AUTHOR]

Catalase (CAT), glutathione peroxidase (GPx), and peroxiredoxin 2 (Prx2) can counteract the deleterious effects of oxidative stress (OS). Their binding to the red blood cell (RBC) membrane has been reported in non-immune hemolytic anemias (NIHAs). Our aim was to evaluate the relationships between CAT, GPx, and Prx2, focusing on their role at the RBC membrane, in hereditary spherocytosis (HS), sickle cell disease (SCD), β-thalassemia (β-thal), and healthy individuals. The studies were performed in plasma and in the RBC cytosol and membrane, evaluating OS biomarkers and the enzymatic activities and/or the amounts of CAT, GPx, and Prx2. The binding of the enzymes to the membrane appears to be the primary protective mechanism against oxidative membrane injuries in healthy RBCs. In HS (unsplenectomized) and β-thal, translocation from the cytosol to the membrane of CAT and Prx2, respectively, was observed, probably to counteract lipid peroxidation. RBCs from splenectomized HS patients showed the highest membrane-bound hemoglobin, CAT, and GPx amounts in the membrane. SCD patients presented the lowest amount of enzyme linkage, possibly due to structural changes induced by sickle hemoglobin. The OS-induced changes and antioxidant response were different between the studied NIHAs and may contribute to the different clinical patterns in these patients. [ABSTRACT FROM AUTHOR]

Gilbert syndrome is a benign condition due to UGT1A1 mutations frequently resulting in mild, indirect hyperbilirubinemia. Inherited hemolytic anemias often present with hyperbilirubinemia and hepatosplenomegaly. Over the years, there have been multiple case reports/series in which the extent of unconjugated hyperbilirubinemia exceeds the extent of anemia. When worked up for the unexplained hyperbilirubinemia, these patients were found to carry mutations corresponding to both immune hemolytic anemia as well as Gilbert syndrome. This article aims to emphasise when to suspect this coexistence and how to approach a patient with inherited hemolytic anemia with unexplained jaundice.

Hereditary spherocytosis (HS) is one of the most common causes of hereditary hemolytic anemia. The current diagnostic guidelines for HS are mainly based on a combination of physical examination and laboratory investigation. However, some patients present with complicated clinical manifestations that cannot be explained by routine diagnostic protocols. Here, we report a rare HS case of mild anemia with extremely high indirect bilirubin levels and high expression of fetal hemoglobin. Using whole exome sequencing analysis, this patient was identified as a heterozygous carrier of a de novo SPTB nonsense mutation (c.605G > A; p.W202*) and a compound heterozygous carrier of known UGT1A1 and KLF1 mutations. This genetic analysis based on the interpretation of the patient's genomic data not only achieved precise diagnosis by an excellent explanation of the complicated phenotype but also provided valuable suggestions for subsequent appropriate approaches for treatment, surveillance and prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to pinpoint pathogenic genes and assess the mutagenic pathogenicity in two pediatric patients with hereditary spherocytosis. Methods: We utilized whole-exome sequencing (WES) for individual analysis (case 1) and family-based trio analysis (case 2). The significance of the intronic mutation was validated through a Minigene splicing assay and supported by subsequent in vitro experiments. Results: Both probands received a diagnosis of hereditary spherocytosis. WES identified a novel ANK1 c.1504-9G>A mutation in both patients, causing the retention of seven nucleotides at the 5' end of intron 13, as substantiated by the Minigene assay. This variant results in a premature stop codon and the production of a truncated protein. In vitro studies indicated a reduced expression of the ANK1 gene. Conclusion: The novel ANK1 c.1504-9G>A variant is established as the causative factor for hereditary spherocytosis, with the c.1504-9G site functioning as a splicing receptor. [ABSTRACT FROM AUTHOR]

Key Clinical Message When a person has both HS and beta‐thalassemia, their clinical symptoms tend to be less severe. This is because these two conditions have contrasting features. If the clinical symptoms and laboratory results cannot be solely attributed to hemolytic anemia, it is important to consider the possibility of another form of hemolytic anemia coexisting. Abstract We present a 26‐year‐old woman who has been experiencing abdominal pain, jaundice, and anemia for the past 15 years. Initially, she was diagnosed with gallstones and splenomegaly, but after a thorough hematology examination conducted by expert colleagues, it was discovered that she had both beta‐thalassemia and hereditary spherocytosis. The osmotic fragility test confirmed this diagnosis. The patient was advised to undergo both splenectomy and cholecystectomy procedures. It is worth noting that the co‐occurrence of these two conditions is rare.

The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxiredoxin 2 (Prx2) are particularly important in erythroid cells. Reticulocytes and other erythroid precursors may adapt their biosynthetic mechanisms to cell defects or to changes in the bone marrow environment. Our aim was to perform a comparative study of the mRNA levels of CAT, GPX1, PRDX2 and SOD1 in reticulocytes from healthy individuals and from patients with hereditary spherocytosis (HS), sickle cell disease (SCD) and β-thalassemia (β-thal), and to study the association between their transcript levels and the reticulocyte maturity indices. In controls, the enzyme mRNA levels were significantly correlated with reticulocyte maturity indices for all genes except for SOD1. HS, SCD and β-thal patients showed younger reticulocytes, with higher transcript levels of all enzymes, although with different patterns. β-thal and HS showed similar reticulocyte maturity, with different enzyme mRNA levels; SCD and HS, with different reticulocyte maturity, presented similar enzyme mRNA levels. Our data suggest that the transcript profile for these antioxidant enzymes is not entirely related to reticulocyte maturity; it appears to also reflect adaptive mechanisms to abnormal erythropoiesis and/or to altered erythropoietic environments, leading to reticulocytes with distinct antioxidant potential according to each anemia. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

AbstractHereditary spherocytosis (HS) is the most common hereditary hemolytic disorder induced by red blood cell (RBC) membrane defect. This study was undertaken to determine mutations in genes associated with RBC membrane defect in patients with HS such as α-spectrin gene (SPTA1), β-spectrin gene (SPTB), ankyrin gene (ANK1), band 3 anion transport gene (SLC4A1) and erythrocyte membrane protein band 4.1 gene (EPB41). Blood samples were collected from 23 unrelated patients with HS. Patients were diagnosed according to the guidelines from the British Society for Hematology. All hematological examinations for the determination of RBC abnormalities and osmotic fragility tests were conducted. Genomic DNA were extracted from peripheral blood cells and coding exons of known genes for hereditary spherocytosis were enriched using Roche/KAPA sequence capture technology and sequenced on an Illumina system via next-generation sequencing (NGS). The data showed that most of the HS patients confirmed splenomegaly and showed elevated reticulocytes and abnormal bilirubin values. NGS analysis identified the heterozygous variant c.5501G > A in the exon 39 of SPTA1 gene, resulted in a Trp1834*, which leads to a premature stop codon and subsequent mRNA degradation (nonsense- mediated decay) or truncation in α spectrin. Moreover, our data also revealed conventional mutations in genes SPTB, ANK, SLC4A1 and EBP41 in severe patients of HS. In short, this is the first report that determined a novel mutation c.5501G > A in SPTA1 gene in the Saudi population. To the best of our knowledge, this variant c.5501G > A has not been described in global literature so far. This novel mutation in SPTA1 gene is unique in the Saudi population. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis in cattle is a disorder resulting from a nonsense mutation in the SLC4A1 gene, which encodes band 3 membrane protein. This membranopathy leads to the production of spherically-shaped RBCs with reduced deformability and a shorter lifespan in circulation. Laboratory diagnosis of hereditary spherocytosis commonly relies on the erythrocyte osmotic fragility test (OFT), which is time- and labour-consuming and can be influenced by preanalytical factors. The aim of the study was to determine the effect of the preanalytical phase on the stability of osmotic fragility and morphological changes in bovine erythrocytes. Blood was collected from the tail vein of Holstein-Friesian cows (n = 20) into tubes with EDTA or lithium heparin. Erythrocyte resistance to haemolysis was measured by the osmotic fragility test immediately after blood collection and 24, 48 and 72 hours after storage at 4℃ or at room temperature. Thin blood smears were also prepared, stained and examined for cell morphology. The results showed that bovine erythrocyte osmotic fragility remains stable during 24-hour storage at 4℃ irrespective of the anticoagulant used. This suggests that OFT can be performed the day after blood collection if blood is stored at 4℃. Bovine erythrocytes stored at room temperature were also found to have reduced osmotic resistance. However, heparin better preserves the osmotic resistance of bovine erythrocytes at room temperature. Erythrocytes undergo changes during storage. The microscopic examination of cell morphology revealed rapid transformation of bovine discocytes into various stages of echinocytes during the first three days of storage. [ABSTRACT FROM AUTHOR]

Background: 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 (SPTB), variants are located in exons and give rise to mRNA defects. However, the genetic characteristics and pathogenic mechanisms of SPTB intronic variants are not completely understood. This study aimed to analyse a rare intronic inversion variant in the SPTB gene associated with HS, and explore the impact of the variant on SPTB mRNA splicing. Method: 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 SPTB gene splicing and expression were affected. Results: Targeted next-generation sequencing identified a novel diseaseassociated intronic inversion variant of the SPTB 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 SPTB mRNA. Conclusion: This study identifies a rare intronic inversion variant in the SPTB gene associated with hereditary spherocytosis. The pathogenic variant can lead to exon 20 skipping and decreased SPTB gene expression. This finding has not been previously reported in any literature. This study can expand the intronic variant spectrum of the SPTB gene, deepen our understanding of HS pathogenesis, and contribute to the genetic diagnosis and clinical management of patients. [ABSTRACT FROM AUTHOR]

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 (n = 17). The sensitivity of the NGS approach, which tests five genes (ANK1 (gene product: ankyrin1), EPB42 (erythrocyte membrane protein band4.2), SLC4A1 (band3), SPTA1 (α-spectrin), and SPTB (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. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

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.

Hereditary spherocytosis (HS) is a membranopathy that impacts the vertical junctions between the cytoskeleton and the plasma membrane of erythrocytes. The gold standard method for diagnosing it is osmotic gradient ektacytometry (OGE). However, access to this technique is scarce. We have devised a straightforward approach utilizing flow cytometry to quantify variations in an osmotic gradient, relying on FSC-H/SSC-H patterns. We studied 14 patients (9 pediatric, 5 adults) and 54 healthy controls (16 pediatric, 38 adults). After assessing the behavior of the samples in several osmolar gradients we selected for the study the 176, 308, and 458 mOsm/kg levels as hypo-osmolar, iso-osmolar, and hyper-osmolar references. We then selected the iso-osmolar point for assessment to determine its efficacy in discriminating between patient and control groups using a receiver operating characteristic curve. In the pediatric group, the area under the curve (AUC) was 1.0, indicating 100% sensitivity and 93.3% specificity. Conversely, in the adult group, the AUC was 0.98, with 80% sensitivity and 90.9% specificity. We introduce a method that is easily replicable and demonstrates high sensitivity and specificity. This technique could prove valuable in the diagnosis of spherocytosis.

Abstract 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.

ABSTRACTBackground 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.

Introduction: Subtotal or total splenectomy are recommended in severe and should be considered in intermediate forms of hereditary spherocytosis (HS). Data on laparoscopic subtotal splenectomy (LSTS) in HS patients are sparse. Methods: Thirty three patients with HS (median age 10.7 years (yrs), range 1.8-15.5) underwent LSTS. Baseline and follow-up investigation included haematological parameters, microscopic analysis of pitted erythrocytes (pitE), and B-cell subpopulations assessed by flow cytometry. Results were compared to those of non-splenectomised HS patients, HS patients after total splenectomy (TS), and healthy individuals. Results: After LSTS, haemoglobin levels were normalised in all patients. During median long-term follow-up of 3.9 yrs (range 1.1-14.9), only four patients presented mild anaemia. Despite re-growing of the remnant spleen none of the patients required a second surgical intervention. As compared to TS, PitE in LSTS patients were significantly lower and indicated normal to only moderately decreased spleen function. Relative but not absolute IgM memory B-cell counts were reduced in both LSTS and TS patients. Conclusions: LSTS is effective for the treatment of patients with HS. A small remnant spleen is sufficient to provide adequate phagocytic function and to induce a pool of IgM memory B-cells. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to present the demographic characteristics, clinical and laboratory features and outcome of our patients with hereditary spherocytosis (HS). Methods: Demographic, clinical, and laboratory data; complications; and splenectomy results were analyzed retrospectively. The severity of the disease was scaled according to Eber's criteria. Results: Sixty-nine patients (42 boys, 27 girls, median age: 3 years) were eligible. Sixty-eight percent of the patients had a history of neonatal jaundice. The complaints at admission were jaundice (71%), fatigue (27.5%), fainting (4.3%), and pallor (4.3%). The median follow-up duration was 8.5 years. According to Eber's criteria, three (4.3%), 57 (82.6%), and nine (13.1%) patients had mild, moderate, and severe diseases, respectively. Thirty-six patients (52.1%) had a splenectomy. Following splenectomy, we observed a significant rise in hemoglobin levels and a decline in indirect bilirubin levels. Post-operative thrombocytosis was common, with a tendency to fall and stabilize after 1 month. There were no thromboembolic complications. Conclusion: In spite of the high rate of consanguinity, familial history of HS, and neonatal jaundice in our study group, the majority of the HS patients were identified relatively late, about 3 years. This finding shows that HS might be insufficiently acknowledged by primary care. Splenectomy, in selected cases, may reduce the need for transfusions. Post-splenectomy transient thrombocytosis is common and has a benign course. [ABSTRACT FROM AUTHOR]

Abstract 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.

Catalase (CAT), glutathione peroxidase (GPx), and peroxiredoxin 2 (Prx2) can counteract the deleterious effects of oxidative stress (OS). Their binding to the red blood cell (RBC) membrane has been reported in non-immune hemolytic anemias (NIHAs). Our aim was to evaluate the relationships between CAT, GPx, and Prx2, focusing on their role at the RBC membrane, in hereditary spherocytosis (HS), sickle cell disease (SCD), β-thalassemia (β-thal), and healthy individuals. The studies were performed in plasma and in the RBC cytosol and membrane, evaluating OS biomarkers and the enzymatic activities and/or the amounts of CAT, GPx, and Prx2. The binding of the enzymes to the membrane appears to be the primary protective mechanism against oxidative membrane injuries in healthy RBCs. In HS (unsplenectomized) and β-thal, translocation from the cytosol to the membrane of CAT and Prx2, respectively, was observed, probably to counteract lipid peroxidation. RBCs from splenectomized HS patients showed the highest membrane-bound hemoglobin, CAT, and GPx amounts in the membrane. SCD patients presented the lowest amount of enzyme linkage, possibly due to structural changes induced by sickle hemoglobin. The OS-induced changes and antioxidant response were different between the studied NIHAs and may contribute to the different clinical patterns in these patients.

• Red blood cell disorders are associated with hypercoagulability state. • Thrombin generation assay evaluates hypercoagulability. • All red blood cell disorders reported hypercoagulability on peak and velocity. • Splenectomy is associated with hypercoagulability in hereditary spherocytosis. • Co-inherited α-thalassemia with sickle cell trait decreased hypercoagulability. [ABSTRACT FROM AUTHOR]

Diagnosis of Hereditary spherocytosis (HS) often requires time-consuming and/or expensive tests. Cryohemolysis test (CHT) is a simple and easy to perform test with high predictive value for HS diagnosis. In this prospective study, we evaluated the diagnostic utility of CHT for the diagnosis of HS. We included 60 suspected HS patients, 18 patients with Autoimmune hemolytic anemia (AIHA) and 120 healthy controls. Among the 60 suspected cases, there were 36 HS cases and 24 with other hemolytic anemias. The mean CHT (%) ± SD for controls, AIHA, other hemolytic anemias, and HS was 6.63 ± 2.79, 6.79 ± 4.36, 6.61 ± 2.76 and 26.7 ± 8.9, respectively. The CHT % was significantly higher in HS group when compared to controls (p = < 0.0001), AIHA (p = < 0.0001) and other hemolytic anemia groups (p = < 0.0001). At a CHT cut off of > 18.3%, the sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of HS in our study were 97.1%, 94.4%, 97.2% and 90.3%, respectively. CHT is a simple and sensitive test for the diagnosis of HS but remains underutilized. The addition of CHT in the diagnostic workup of HS will be very useful, especially in a resource limited setting. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic disorders. Here, two unrelated families with the probands displaying typical manifestations of HS were enrolled. Our study aimed to characterize the effect of two novel variants in HS patients on gene splicing to help minimize the rate of misdiagnosis of HS and enhance clinicians’ understanding of the disease. Participants and methods A retrospective review was conducted. Peripheral blood samples were collected from all the family members, and genomic DNA was extracted for genetic diagnostics. First, high-throughput sequencing technology was used for the preliminary screening of candidate causative variants. Thereafter, the variants were verified via Sanger sequencing. Furthermore, a pathogenicity analysis of the detected variants was performed including in silico prediction and in vitro experiments. We constructed matched wild-type and mutant-type minigene plasmid of ANK1 based on HEK293T cells to address the effects of variants on mRNA splicing. Results The c.1305 + 2 T > A (family1) and c.1305 + 2del (family2) variants were detected in the ANK1 gene. These two de novo mutations described by us which have not been reported prior to this study. Moreover, the validation results of splicing reporter systems revealed that the intronic mutations resulted in abnormal pre-mRNA splicing. Specifically, the minigene plasmid expressing the c.1305 + 2 T > A variant transcribed the two aberrant transcripts: r.1305_1306ins1305 + 1_1305 + 229 and r.1305_1306ins1305 + 1_1305 + 552. The minigene plasmid expressing c.1305 + 2del transcribed the two aberrant transcripts: r.1305_1306ins1305 + 1_1305 + 228 and r.1305_1306ins1305 + 1_1305 + 551. Conclusion The two de novo variants identified in the ANK1 gene were the genetic etiology of the probands with HS in our study. Our findings further enrich the HS genotype database and provide a basis for genetic counselling and molecular diagnosis.

Abstract Background The incidence of hereditary spherocytosis (HS) is approximately 1:2000 in the western population, while it is much lower in the Chinese population. It is difficult to make a definite diagnosis due to the variable genotypic features and the lack of well-documented evidence for HS patients. Gene sequence examination is helpful for clear diagnosis. Case presentation: We presented the case of a 29-year-old male HS patient with skin yellowness, anorexia, and cholecystolithiasis as the first manifestations. Laboratory examination of the patient and his parents showed a mild reduction in hemoglobin and mean corpuscular hemoglobin concentration, increased reticulocytes, and promotion of indirect bilirubin in the patient and his father. Furthermore, small globular red blood cells with increased osmotic fragility were observed. In particular, the eosin-5’-maleimide binding test provided the strong evidence that band 3 protein was deleted in the erythrocyte membrane. Next-generation sequencing (NGS) and Sanger sequencing further demonstrated a heterozygous nonsense variant (exon16, c.G1985A: p.W662X) in SLC4A1, inherited from his father. Thus, the patient was diagnosed with HS, and then was effectively treated. After splenectomy, the anemia was relieved without any obvious unpleasant side effects. Conclusion We report an extremely rare case of HS in China that presented with hereditary hemolytic anemia with band 3 deletion resulting from a novel variant of SLC4A1, and systematically review a large number of related literatures. This study, therefore, significantly contributes to the literature on HS.

Samuel Sahile Kebede,1 Aregawi Yalew,2 Tesfaye Yesuf,3 Getachew Mesfin Bambo,1 Tadesse Duguma,1 Berhanu Woldu2 1Department of Medical Laboratory Sciences, College of Medicine and Health Sciences, Mizan Tepi University, Mizan, Ethiopia; 2Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia; 3Department of Internal Medicine School of Medicine, University of Gondar, Gondar, EthiopiaCorrespondence: Samuel Sahile Kebede, Tel +251917768545, Email samissahile45@gmail.comBackground: Hereditary spherocytosis is a type of hemolytic anemia characterized by a clinically heterogeneous, genetically defined red blood cell membrane abnormality that results in hemolytic crisis. The inheritance of HS is autosomal dominant in 80% of affected individuals and recessive genes or sporadic type in the remaining 20%.Objective: The main aim of this study was to determine the magnitude of immune hereditary spherocytosis among human immunodeficiency virus-infected adults at the University of Gondar comprehensive specialized hospital in northwest Ethiopia from March to April 2021.Methods: An institution-based cross-sectional study was conducted on 358 human immunodeficiency virus-infected adults selected by systematic random sampling at the University of Gondar comprehensive specialized hospital from March to April 2021. Data for socio-demographic data were collected by structured pretested questionnaire. Five ml of venous blood was drawn from each participant and analyzed by Unicel DHX 800 hematology analyzer, and blood film examination and antihuman globulin test were performed to exclude immune hemolytic anemia. Data was entered into Epidata version 4.6 and analyzed by STATA version 14. Descriptive statistics were computed and drawn in charts and graphs.Results: The prevalence of hereditary spherocytosis was 2 of 358 participants. Both individuals who developed hereditary spherocytosis were females and in the age group of 22 to 35. The overall prevalence of anemia was 91 (25.42%). Of those anemic study population 3 (3.29%), 28 (30.77%), and 60 (65.93%), respectively, had severe, moderate, and mild anemia.Conclusion and Recommendation: Hereditary spherocytosis is a less frequent condition in human immunodeficiency virus-infected adults. In these patients, early detection and treatment are necessary at the familial level by using a test algorithm.Keywords: anemia, hereditary spherocytosis, spherocytosis, HIV/AIDS

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Inflammatory myofibroblastic tumors are a rare subset of lung lesions in the adult age group. They pose a diagnostic challenge as they present with non-specific findings. We report a 27-year-old female with an inflammatory myofibroblastic tumor on a background of hereditary spherocytosis. [ABSTRACT FROM AUTHOR]

Gallstones are common in hereditary spherocytosis (HS) and other chronic hemolytic diseases, with most affected patients being asymptomatic. Whether and how asymptomatic gallstones should be treated is controversial. We conducted a retrospective cohort study of pediatric patients with HS and asymptomatic gallstones to compare the clinical outcomes between the observation group (followed up with gallstones in situ) and the intervention group (cholecystectomy or cholecystolithotomy). The primary outcome was the composite of adverse outcomes, including gallstone-associated, gallbladder surgery-associated, and splenectomy-associated events. Secondary outcomes included the changes in the size and number of gallstones and the recurrence of gallstones. Fifty-two patients were included (38 in the observation group and 14 in the intervention group), with a mean follow-up length of 5.2 years. Patients in the intervention group had a lower incidence of primary outcomes (7.1% vs. 42.1%) than patients in the observation group (OR, 0.12; 95%CI, 0.01–0.99). Patients with gallstones >5 mm in diameter had the highest risk of adverse events (47.4%). In the observation group, gallstone growth, disappearance, and stability were observed in 19.4%, 29.0%, and 51.6% of splenectomized HS patients, respectively. Small gallstones (diameter ≤5 mm) or sludge were more likely to be associated with disappearance (P = 0.04). Most asymptomatic gallstones grow or persist in splenectomized HS patients for an extended period. Surgical treatment of asymptomatic gallstones in HS patients requiring splenectomy is associated with a lower risk of adverse outcomes. III (retrospective comparative study). • What is currently known about this topic? • For HS patients without gallstones, prophylactic cholecystectomy is not recommended. For HS patients with symptomatic gallstones, cholecystectomy should be performed. • What new information is contained in this article? • Most asymptomatic gallstones would progress or persist in HS patients, yielding a high risk of gallstone-related adverse outcomes. Concomitant surgical procedures are encouraged. [ABSTRACT FROM AUTHOR]

Hereditary Spherocytosis (HS) is a common cause of hemolytic anemia varying from mild to severe hemolysis due to defects in red cell membrane protein genes, namely ANK1, SPTB, SPTA1, SLC4A1, and EPB42. These genes are considerably very large spaning 40–50 exons making gene-by-gene analysis costly and laborious by conventional methods. In this study, we explored 26 HS patients harboring 21 ANK1 variants identified by next-generation sequencing (NGS), characteristics and spectrum of the detected ANK1variants were analyzed in this study. Clinically, all the HS patients showed moderate to severe transfusion-dependent hemolytic anemia, some requiring splenectomy. We identified 13 novel and 8 reported variants, mainly 9 frameshifts, 2 missense, 6 nonsense, and 4 splice site ANK1 variants, using NGS technology. Frameshifts were remarkably the most common variant type seen in Indian HS patients with ANK1 gene defects. We have also explored expression levels of red cell membrane ankyrin protein by flow cytometry in 14 HS patients with ANK1 gene defects and a significant reduction in ankyrin protein expression has been found. This report mainly illustrates the molecular and phenotypic heterogeneity of ANK1 variants causing HS in Indian patients. Ankyrin-1 mutations are a significant cause of loss of function in dominant HS in the Indian population. Comprehensive genetic and phenotypic evaluation assists in implementing the knowledge of genetic patterns and spectrum of ANK1 gene variants, providing molecular support for HS diagnosis. [ABSTRACT FROM AUTHOR]

We report a case of severe anemia caused by complex hereditary spherocytosis (HS) and X-linked sideroblastic anemia (XLSA) with two mutations in the spectrin beta (SPTB) and 5-aminolevulinic acid synthase (ALAS2) genes. The proband was a 16-year-old male with severe jaundice and microcytic hypochromic anemia since his childhood. He had more severe anemia requiring erythrocyte transfusion, and had no response to vitamin B6 treatment. Next-generation sequencing (NGS) revealed double heterozygous mutations, one in exon 19 (c.3936G > A:p.W1312X) of the SPTB gene and another in exon 2 (c.37A > G:p.K13E) of the ALAS2 gene, and confirmed again by Sanger sequencing. The mutation of ALAS2 (c.37A > G) is inherited from his asymptomatic heterozygous mother, causing amino acid p.K13E, and the mutation has not yet been reported. The mutation of SPTB (c.3936G > A) is a nonsense mutation, leading to a premature termination codon in exon 19, and the mutation in the SPTB gene is not found in any of his relatives, which indicates a de novo monoallelic mutation. Conclusions: The double heterozygous mutations in the SPTB and ALAS2 genes lead to the joint occurrence of HS and XLSA in this patient, and are implicated in the more severe clinical phenotypes. [ABSTRACT FROM AUTHOR]