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Clinical Case Reports Jun 2022Hemolytic crises and aplastic crises in hereditary spherocytosis (HS) are most commonly triggered by viral infections. We present the case of an adolescent girl with HS...
Hemolytic crises and aplastic crises in hereditary spherocytosis (HS) are most commonly triggered by viral infections. We present the case of an adolescent girl with HS who developed unexpected and life-threatening complications of her inherited hemolytic anemia as a consequence of anorexia nervosa and severe malnutrition.
PubMed: 35662786
DOI: 10.1002/ccr3.5841 -
Internal Medicine (Tokyo, Japan) Jan 2023Most patients with hereditary spherocytosis (HS) have a family history of disease, while those without such a history are difficult to diagnose. We herein report a case...
Most patients with hereditary spherocytosis (HS) have a family history of disease, while those without such a history are difficult to diagnose. We herein report a case of HS with no family history harboring a novel heterozygous mutation of SPTA1, c.2161G>A (p.E721K), and a homozygous polymorphism of UGT1A1*6. In silico analyses suggested that the mutation might contribute to the pathogenesis of HS. The coexistence of HS and Gilbert's syndrome increases the risk of gallstones. Therefore, splenectomy, alone or in combination with cholecystectomy, is recommended. The determination of genetic diathesis provides useful information for the management of hemolytic anemia.
Topics: Humans; Gilbert Disease; Mutation; Spherocytosis, Hereditary; Heterozygote; Glucuronosyltransferase; Polymorphism, Genetic; Cytoskeletal Proteins
PubMed: 35650129
DOI: 10.2169/internalmedicine.9478-22 -
Children (Basel, Switzerland) Apr 2022The aim of this paper is to assess the effectiveness and perioperative complications of splenic surgeries in children. In 41 splenectomies, an anterior abdominal...
The aim of this paper is to assess the effectiveness and perioperative complications of splenic surgeries in children. In 41 splenectomies, an anterior abdominal laparoscopic approach was used, with 35 including a partial laparoscopic splenectomy. Of these, three needed a conversion to open. Six patients had a total splenectomy, three of which were open. Patients ranged in age from 5 to 18 years. Splenectomy was performed for a variety of causes, including hereditary spherocytosis ( = 20), splenic cysts ( = 13), sickle cell disease ( = 3), primary malignancy ( = 1), sepsis ( = 1), embolism ( = 1), anemia ( = 1), and hypersplenism ( = 1). The average length of stay was 7.6 days, and the average operation time was 169.3 min. Pleural effusion in the left hemithorax was found in 31.6% of the patients, with 5.3% requiring a thorax drain. The majority of patients had the highest platelet count two weeks after surgery. There was no evidence of wound infection, pancreatic leak, colon perforation, or postoperative sepsis. The most encountered perioperative complication was bleeding with the need of transfusion ( = 6), and one patient needed a diaphragm repair. A partial splenectomy (PS) can be a difficult procedure with a steep learning curve. For most children who require a splenic operation, this should be the primary procedure of choice.
PubMed: 35626782
DOI: 10.3390/children9050605 -
Radiology Case Reports Jul 2022Accessory spleen rupture can induce acute abdominal bleeding following minimal trauma or by atraumatic mechanisms. Spleen rupture is more frequent in pediatric patients...
Accessory spleen rupture can induce acute abdominal bleeding following minimal trauma or by atraumatic mechanisms. Spleen rupture is more frequent in pediatric patients and those affected by hematological diseases. We described the case of a 59-year-old male patient affected by hereditary spherocytosis referred to the emergency department for abdominal left side pain. An early ultrasound performed in the emergency department allowed to diagnosed hemoperitoneum by spontaneous bleeding of hypertrophic accessory spleen. Although abdomen computed tomography is the diagnostic method of choice, ultrasound can early detect sign of emoperitoneum in the emergency setting in case of hemodinamically unstable patient.
PubMed: 35570881
DOI: 10.1016/j.radcr.2022.04.014 -
American Journal of Human Genetics Jun 2022The spleen plays a key role in iron homeostasis. It is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this role,...
The spleen plays a key role in iron homeostasis. It is the largest filter of the blood and performs iron reuptake from old or damaged erythrocytes. Despite this role, spleen iron concentration has not been measured in a large, population-based cohort. In this study, we quantify spleen iron in 41,764 participants of the UK Biobank by using magnetic resonance imaging and provide a reference range for spleen iron in an unselected population. Through genome-wide association study, we identify associations between spleen iron and regulatory variation at two hereditary spherocytosis genes, ANK1 and SPTA1. Spherocytosis-causing coding mutations in these genes are associated with lower reticulocyte volume and increased reticulocyte percentage, while these common alleles are associated with increased expression of ANK1 and SPTA1 in blood and with larger reticulocyte volume and reduced reticulocyte percentage. As genetic modifiers, these common alleles may explain mild spherocytosis phenotypes that have been observed clinically. Our genetic study also identifies a signal that co-localizes with a splicing quantitative trait locus for MS4A7, and we show this gene is abundantly expressed in the spleen and in macrophages. The combination of deep learning and efficient image processing enables non-invasive measurement of spleen iron and, in turn, characterization of genetic factors related to the lytic phase of the erythrocyte life cycle and iron reuptake in the spleen.
Topics: Biological Specimen Banks; Cytoskeletal Proteins; Genome-Wide Association Study; Hemolysis; Homeostasis; Humans; Iron; Magnetic Resonance Imaging; Mutation; Spherocytosis, Hereditary; Spleen; United Kingdom
PubMed: 35568031
DOI: 10.1016/j.ajhg.2022.04.013 -
American Journal of Hematology Aug 2022
Topics: Aged; Ankyrins; Clonal Hematopoiesis; Hematopoiesis; Humans; Mutation; Spherocytosis, Hereditary
PubMed: 35560067
DOI: 10.1002/ajh.26593 -
Cells Mar 2022Background: Hereditary spherocytosis (HS) and pyruvate kinase deficiency (PKD) are the most common causes of hereditary chronic hemolytic anemia. Here, we describe...
Concomitant Hereditary Spherocytosis and Pyruvate Kinase Deficiency in a Spanish Family with Chronic Hemolytic Anemia: Contribution of Laser Ektacytometry to Clinical Diagnosis.
Background: Hereditary spherocytosis (HS) and pyruvate kinase deficiency (PKD) are the most common causes of hereditary chronic hemolytic anemia. Here, we describe clinical and genetic characteristics of a Spanish family with concomitant β-spectrin (SPTB) c.647G>A variant and pyruvate kinase (PKLR) c.1706G>A variant. Methods: A family of 11 members was studied. Hematological investigation, hemolysis tests, and specific red cell studies were performed in all family members, according to conventional procedures. An ektacytometric study was performed using the osmoscan module of the Lorca ektacytometer (MaxSis. RR Mechatronics). The presence of the SPTB and PKLR variants was confirmed by t-NGS. Results: The t-NGS genetic characterization of the 11 family members showed the presence of a heterozygous mutation for the β-spectrin (SPTB; c.647G>A) in seven members with HS, three of them co-inherited the PKLR variant c.1706G>A. In the remaining four members, no gene mutation was found. Ektacytometry allowed a clear diagnostic orientation of HS, independently from the PKLR variant. Conclusions: This family study allows concluding that the SPTB mutation, (c.647G>A) previously described as likely pathogenic (LP), should be classified as pathogenic (P), according to the recommendations for pathogenicity of the American College of Medical Genetics and the Association for Molecular Pathology. In addition, after 6 years of clinical follow-up of the patients with HS, it can be inferred that the chronic hemolytic anemia may be attributable to the SPTB mutation only, without influence of the concomitant PKLR. Moreover, only the family members with the SPTB mutation exhibited an ektacytometric profile characteristic of HS.
Topics: Anemia, Hemolytic, Congenital Nonspherocytic; Humans; Lasers; Pyruvate Kinase; Pyruvate Metabolism, Inborn Errors; Spectrin; Spherocytosis, Hereditary
PubMed: 35406697
DOI: 10.3390/cells11071133 -
BMC Surgery Apr 2022Hereditary spherocytosis (HS) complicated by splenic infarction is very rare, and it is even rarer to develop splenic infarction after infectious mononucleosis (IM) as a... (Review)
Review
BACKGROUND
Hereditary spherocytosis (HS) complicated by splenic infarction is very rare, and it is even rarer to develop splenic infarction after infectious mononucleosis (IM) as a result of Epstein-Barr virus (EBV) infection. Therefore, misdiagnosis or missed diagnosis is prone to occur.
CASE PRESENTATION
A 19-year-old Chinese female previously diagnosed with HS was admitted to our institution with persistent high fever and icterus. On admission, the physical examination showed anemia, jaundice, marked splenomegaly, obvious tenderness in the left upper abdomen (LUA). Peripheral blood film shows that spherical red blood cells accounted for about 6%, and Immunoglobulin M (IgM) antibodies specific to Epstein-Barr virus (EBV) viral capsid antigen were detected. An abdominal CT scan revealed a splenic infarction. The patient was diagnosed with HS with splenic infarction following EBV infection and underwent an emergency laparoscopic splenectomy (LS). Pathological analysis showed a splenic infarction with red pulp expansion, white pulp atrophy and a splenic sinus filled with red blood cells. After two months of follow-up visits, the patient showed no signs of relapse.
CONCLUSIONS
HS complicated by splenic infarction is very rare and mostly occurs in men under 20 years of age and is often accompanied by other diseases, such as sickle cell traits (SCT) or IM. Although symptomatic management may be sufficient, emergency laparoscopic splenectomy may be safe and effective when conservative treatment is ineffective.
Topics: Adult; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Male; Spherocytosis, Hereditary; Splenic Infarction; Young Adult
PubMed: 35397569
DOI: 10.1186/s12893-022-01580-5 -
Insect Biochemistry and Molecular... May 2022Phenoloxidase (PO) is a crucial component of the insect immune response against microbial infection. In the tobacco hornworm Manduca sexta, PO is generated from its...
Phenoloxidase (PO) is a crucial component of the insect immune response against microbial infection. In the tobacco hornworm Manduca sexta, PO is generated from its precursor proPO by prophenoloxidase activating proteases (PAPs) in the presence of two noncatalytic serine protease homologs (SPHs). cDNA cloning and genome analysis indicate that SPH1a (formerly known as SPH1), SPH1b, SPH4, SPH101, and SPH2 contain a clip domain, a linker, and a protease-like domain (PLD). The first 22 residues of the SPH1b, SPH4, and SPH101 PLDs are identical, and differ from SPH1a only at position 4, Thr substituted with Asn in SPH1a. While the sequence from Edman degradation was used to establish PAP cofactor as a high M complex of SPH1a and SPH2, this assignment needed further validation, especially because SPH1b mRNA levels are much higher than SPH1a's and better correlate with SPH2 transcription. Thus, here we determined expression profiles of these SPH genes in different tissues from various developmental stages using highly specific primers. High levels of SPH1b and SPH2 proteins, low SPH4, and no SPH1a or SPH101 were detected in hemolymph from larvae in the feeding, wandering and bar stages, pupae, and adults by targeted LC-MS/MS analysis, based on unique peptides from the trypsin-treated SPHs. We expressed the five proSPHs in baculovirus-infected Sf9 cells for use as standards to identify and quantify their counterparts in plasma samples. Moreover, we tested their cleavage by PAP3 and efficacy of the SPH1a, 1b, 4, and 101 as SPH2 partners in PAP3-mediated proPO activation. PAP3 processed proSPH1b and 101 more readily than proSPH1a and 4; PAP3 activated proPO more efficiently in the presence of SPH2 with SPH101 or SPH1b than with SPH1a or SPH4. These results generally agree with their order of appearance or sequence similarity: SPH101 > SPH1b (98%) > SPH1a (90%) > SPH4 (83%). In other words, likely due to positive selection, products of the newly duplicated genes (SPH1b and SPH101) are more favorable substrates of PAP3 and better SPH2 partners in forming a high M cofactor than SPH1a or SPH4 is. Electrophoresis on native gel and immunoblot analysis further indicated that SPH101 or 1b form high M complexes more readily than SPH1a or 4 does. In comparison, SPH2 showed a small mobility decrease and then increase on native gel after PAP3 cleavage at the first site. Since the natural cofactor in bar-stage hemolymph is complexes of SPH1 and 2 with an average M of 790 kDa, PAP3-activated SPH2 may associate with the higher M SPH1b scaffolds to form super-complexes. Their structures and formation in relation to cleavage of SPH1b at different sites await further exploration.
Topics: Animals; Ankyrins; Catechol Oxidase; Chromatography, Liquid; Enzyme Precursors; Hemolymph; Insect Proteins; Manduca; Monophenol Monooxygenase; Serine Endopeptidases; Serine Proteases; Spherocytosis, Hereditary; Tandem Mass Spectrometry
PubMed: 35395380
DOI: 10.1016/j.ibmb.2022.103762