-
Deutsches Arzteblatt International Dec 2022
Topics: Humans; Child; Adolescent; Splenectomy; Spherocytosis, Hereditary; Spleen; Laparoscopy
PubMed: 36814423
DOI: 10.3238/arztebl.m2022.0288 -
Acta Medica Portuguesa Jun 2023Even though it is a rare condition, hereditary spherocytosis (EH) is the main inherited cause of haemolytic anaemia and presents with a broad spectrum of symptoms. In...
Even though it is a rare condition, hereditary spherocytosis (EH) is the main inherited cause of haemolytic anaemia and presents with a broad spectrum of symptoms. In the few reported cases of pregnancy and EH, maternal and foetal outcomes are controversial. Particularly, reports of pregnancies with EH associated with thrombosis or portal hypertension are scarce. We present a case of a woman who underwent splenectomy with EH and non-cirrhotic portal hypertension. Our patient presented polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibit-1 that have a controversial impact on thrombotic risk. During pregnancy, the woman showed no signs of haemodynamical or cirrhosis deterioration. Concerning the foetus, late-onset foetal growth restriction was diagnosed but did not determine preterm delivery. Five weeks post-partum after an episode of acute abdominal pain, mesenteric venous thrombosis was diagnosed. In this case report, we describe our experience in managing pregnancy, labour and post-partum of a woman with EH, highlighting potential complications of this condition.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Spherocytosis, Hereditary; Hypertension, Portal; Splenectomy; Premature Birth
PubMed: 36753998
DOI: 10.20344/amp.18871 -
Blood Advances Sep 2023Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism...
Splenectomy improves the clinical parameters of patients with hereditary spherocytosis, but its potential benefit to red blood cell (RBC) functionality and the mechanism behind this benefit remain largely overlooked. Here, we compared 7 nonsplenectomized and 13 splenectomized patients with mutations in the β-spectrin or the ankyrin gene. We showed that hematological parameters, spherocyte abundance, osmotic fragility, intracellular calcium, and extracellular vesicle release were largely but not completely restored by splenectomy, whereas cryohemolysis was not. Affected RBCs exhibited decreases in β-spectrin and/or ankyrin contents and slight alterations in spectrin membrane distribution, depending on the mutation. These modifications were found in both splenectomized and nonsplenectomized patients and poorly correlated with RBC functionality alteration, suggesting additional impairments. Accordingly, we found an increased abundance of septins, small guanosine triphosphate-binding cytoskeletal proteins. Septins-2, -7, and -8 but not -11 were less abundant upon splenectomy and correlated with the disease severity. Septin-2 membrane association was confirmed by immunolabeling. Except for cryohemolysis, all parameters of RBC morphology and functionality correlated with septin abundance. The increased septin content might result from RBC maturation defects, as evidenced by (1) the decreased protein 4.2 and Rh-associated glycoprotein content in all patient RBCs, (2) increased endoplasmic reticulum remnants and endocytosis proteins in nonsplenectomized patients, and (3) increased lysosomal and mitochondrial remnants in splenectomized patients. Our study paves the way for a better understanding of the involvement of septins in RBC membrane biophysical properties. In addition, the lack of restoration of septin-independent cryohemolysis by splenectomy may call into question its recommendation in specific cases.
Topics: Humans; Spectrin; Septins; Splenectomy; Ankyrins; Spherocytosis, Hereditary; Erythrocytes
PubMed: 36753606
DOI: 10.1182/bloodadvances.2022009114 -
Central-European Journal of Immunology 2022Autoimmune lymphoproliferative syndrome (ALPS) is a chronic non-malignant lymphoproliferative disorder caused by mutations in the genes involved in programmed cell...
Autoimmune lymphoproliferative syndrome (ALPS) is a chronic non-malignant lymphoproliferative disorder caused by mutations in the genes involved in programmed cell death. It is inherited as an autosomal dominant pattern with variable penetrance. In this paper we present the first report of a Macedonian family with ALPS, caused by a novel heterozygous variant in the FAS gene. The next generation sequencing (NGS) analysis in a patient with splenomegaly, suspected for hereditary spherocytosis, showed presence of the FAS c.913dupA, p.Thr305AsnfsTer16 variant. The same variant was present in the patient's mother, but not in the mother's parents (proband's grandparents). Thus, the pathogenic FAS variant has arisen as a de novo event in the proband's mother. Later, analysis of the newborn affected sister showed presence of the same FAS variant. Additional clinical and laboratory investigations in the proband and her sister confirmed the presence of specific biomarkers for ALPS. A first-line NGS analysis allows identification of the genetic defect and initiation of appropriate clinical examinations to promptly establish the clinical diagnosis in patients with rare diseases. Reverse phenotyping in our case provided a prompt and accurate diagnosis and early initiation of specific therapy.
PubMed: 36751388
DOI: 10.5114/ceji.2022.118079 -
Medicine Jan 2023Hereditary spherocytosis (HS) has a defect in the vertically connected proteins on the cell membrane of red blood cells (RBC). Hereditary elliptocytosis (HE) has a... (Review)
Review
A large family of hereditary spherocytosis and a rare case of hereditary elliptocytosis with a novel SPTA1 mutation underdiagnosed in Taiwan: A case report and literature review.
RATIONALE
Hereditary spherocytosis (HS) has a defect in the vertically connected proteins on the cell membrane of red blood cells (RBC). Hereditary elliptocytosis (HE) has a defect in proteins that connect the cell membrane horizontally. We reported two families of RBC membrane disorders in Taiwanese, one was HS and the other was HE.
PATIENT CONCERNS
Case 1. A 19-year-old male student with chronic jaundice and splenomegaly. His mother, maternal uncle, grandmother, and many members of older generations also had splenomegaly and underwent splenectomy. Case 2. A 40-year-old man has experienced pallor and jaundice since the age of 20 and was found to have splenomegaly, and gall bladder stones in the older age. His younger sister also had pallor and jaundice for a long time.
DIAGNOSES
In case 1, a peripheral blood smear showed 20% spherocytes. Eosin-5-maleimide labeled RBC by flow cytometry showed a result of 30.6 MCF (cutoff value: 45.5 MCF). He was diagnosed with HS. The gene analysis identified a heterozygous mutation with c.166A > G (p.Lys56Glu) in the SLC4A1 gene in this proband, his mother, and maternal uncle. In case 2, more than 40% of ellipsoid RBC present in the peripheral blood smear. He was diagnosed with HE. Genetic analysis of the SPTA1 gene identified a novel heterozygous exon2, c.86A > C, p.Gln29Prol mutation.
INTERVENTIONS
The two patients had compensated anemia, clinical follow-up instead of splenectomy was done.
OUTCOMES
The two patients had normal daily activities and lives.
LESSONS
We reported two Taiwanese families, one was hereditary spherocytosis affected by a heterozygous mutation with c.166A > G (p.Lys56Glu) in SLC4A1, and the other was hereditary elliptocytosis caused by a novel heterozygous SPTA1 gene mutation, c. 86A > C, p.Gln29Prol. These 2 seemingly common hereditary red blood cell membrane protein defects induced by hemolysis are usually underdiagnosed or misdiagnosed.
Topics: Adult; Female; Humans; Male; Young Adult; Cytoskeletal Proteins; Elliptocytosis, Hereditary; Jaundice; Mutation; Pallor; Spherocytosis, Hereditary; Splenomegaly; Taiwan
PubMed: 36705355
DOI: 10.1097/MD.0000000000032708 -
Blood Jan 2023
Topics: Humans; Hematologic Diseases; Spherocytosis, Hereditary
PubMed: 36701166
DOI: 10.1182/blood.2022018195 -
Indian Journal of Nuclear Medicine :... 2022We present a case of a 23-year-old male patient with complaints of fever, cough, and persistent anemia for the past 6 months and with a known history of hereditary...
We present a case of a 23-year-old male patient with complaints of fever, cough, and persistent anemia for the past 6 months and with a known history of hereditary spherocytosis. Computed tomography (CT) thorax demonstrated multiple paravertebral lesions in the bilateral thoracic cavities, suggestive of lymphadenopathy; subsequently, Flurodeoxyglucose PET/CT was done with suspicion of lymphoma, which showed no significant metabolic activity in those lesions. Thus, in view of clinical and metabolic status, lesions were considered extramedullary hematopoiesis (EMH). This case highlights the importance of considering EMH, while interpreting suspicious lymphadenopathy in cases of chronic anemia and also possible scan findings in the same.
PubMed: 36686299
DOI: 10.4103/ijnm.ijnm_10_22 -
Life (Basel, Switzerland) Jan 2023Previously, we reported a new missense mutation in the gene that correlated with the hereditary spherocytosis phenotype. This mutation, resulting in L1340P substitution...
Previously, we reported a new missense mutation in the gene that correlated with the hereditary spherocytosis phenotype. This mutation, resulting in L1340P substitution (HGMD CM149731), likely leads to the changes in the conformation of the ankyrin ZZUD domain important for ankyrin binding to spectrin. Here, we report the molecular and physiological effects of this mutation. First, we assessed the binding activity of human β-spectrin to the mutated ZZUDL1340P domain of ankyrin using two different experimental approaches-the study of association and dissociation responses of the spectrin-ankyrin binding domain and a sedimentation assay. In addition, we documented the changes in morphology caused by the overexpressed ankyrin ZZUD domain in human cell models. Our results prove the key role of the L1340 aa residue for the correct alignment of the ZZUD domain of ankyrin, which results in binding the latter with spectrin within the erythrocyte membrane. Replacing L1340 with a proline residue disrupts the spectrin-binding activity of ankyrin.
PubMed: 36676098
DOI: 10.3390/life13010151 -
BMC Pediatrics Jan 2023Hereditary spherocytosis (HS) is one of the most common hereditary haemolytic disorders. Here, two unrelated families with the probands displaying typical manifestations...
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.
Topics: Child; Humans; Ankyrins; East Asian People; HEK293 Cells; Mutation; RNA Precursors; Spherocytosis, Hereditary
PubMed: 36647015
DOI: 10.1186/s12887-022-03795-0 -
Human Vaccines & Immunotherapeutics Dec 2023Herein, we report the case of a 22-year-old woman with hereditary spherocytosis (HS) whose condition worsened after administration of the coronavirus disease 2019...
Herein, we report the case of a 22-year-old woman with hereditary spherocytosis (HS) whose condition worsened after administration of the coronavirus disease 2019 (COVID-19), mRNA vaccine 'BNT162b2 Pfizer-BioNTech.' The woman had been diagnosed with HS in 2005, and her condition remained stable until February 2021. In March 2021, she received the first dose of the above vaccine and experienced pain at the injection site. After the second dose in April 2021, she developed fever and general malaise. Investigations revealed progression of hemolysis, which improved after a few days. To the best of our knowledge, this is the first report of progression of hemolysis in a patient with HS after administration of the mRNA vaccine COVID-19, BNT162b2 'Pfizer-BioNTech.'
Topics: Humans; Female; Young Adult; Adult; COVID-19 Vaccines; BNT162 Vaccine; Hemolysis; COVID-19; mRNA Vaccines
PubMed: 36625832
DOI: 10.1080/21645515.2023.2165381