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Cureus Feb 2024Hereditary spherocytosis/elliptocytosis is a non-immune hemolytic anemia caused by an alteration in the erythrocyte membrane that predisposes the cell to its lysis. This...
Hereditary spherocytosis/elliptocytosis is a non-immune hemolytic anemia caused by an alteration in the erythrocyte membrane that predisposes the cell to its lysis. This report presents a case of a 42-year-old woman with a history of spontaneous abortion, associated with postpartum bleeding, chronic anemia, and premature menopause. After five years, she consulted due to alterations in the state of consciousness and severe symptomatic hyponatremia, with a diagnosis of hypopituitarism, explained by a late Sheehan syndrome. During hospitalization, she developed non-immune hemolytic anemia associated with a positive osmotic fragility test. A diagnosis of hereditary spherocytosis/elliptocytosis was made. We correlate blood hypoosmolarity as a trigger with the in vitro hypotonic solution of the osmotic fragility test for the diagnosis of this disease. This association is not reported in the literature; in our case, we show the concomitant improvement of anemia with the increase in sodium levels and hormonal replacement.
PubMed: 38435165
DOI: 10.7759/cureus.53417 -
Journal of Clinical Laboratory Analysis Mar 2022Hereditary spherocytosis (HS) is characterized by decreased erythrocyte deformability resulting in hemolytic anemia. This is a heterogeneous disease regarding underlying...
INTRODUCTION
Hereditary spherocytosis (HS) is characterized by decreased erythrocyte deformability resulting in hemolytic anemia. This is a heterogeneous disease regarding underlying protein deficiency, disease severity, age at diagnosis and clinical course. Although largely considered as pediatric disease, HS could be initially diagnosed also in elder patients as a result of gallstones or splenomegaly fortuitous finding. Concurrently, common adulthood metabolic disorders like diabetes or dyslipidemia are also known to impair RBC rheology and deformability. Therefore, we aimed to investigate if these diseases affect the screening and diagnostic tools used for HS diagnosis.
METHODS
We applied our workflow for HS diagnosis on 95 pathological samples: 29 patients with diabetes, 20 with hypercholesterolemia, 17 with dyslipidemia, 6 with hypertriglyceridemia, 23 with metabolic syndrome (MS). Thus, a total of 73 samples were analyzed by automated reticulocyte analysis, 52 by cryohemolysis test, and 41 by ektacytometry osmoscan analysis as we used two out of the three tests for each individual sample.
RESULTS
Applying our screening algorithm based on automated reticulocyte indices, a total of 4 samples (4.2%): one sample (5%) from the diabetes group and three samples (16.7%) from the MS group, positioned into the HS zone. However, no significant difference was found between any of the pathological groups and the controls for the cryohemolysis test or the osmoscan.
CONCLUSION
While diabetes and hypercholesterolemia are pathologic conditions known to present with decreased erythrocyte deformability and disturbed rheology, their possible concomitant presence with HS would not interfere with the screening and confirmatory laboratory methods.
Topics: Adult; Aged; Child; Diabetes Mellitus; Humans; Hypercholesterolemia; Reticulocytes; Spherocytosis, Hereditary
PubMed: 35080062
DOI: 10.1002/jcla.24248 -
Frontiers in Medicine 2022The clinical manifestations of hereditary spherocytosis are similar to those of various hemolytic anemias, which causes hereditary spherocytosis to be difficult to...
The clinical manifestations of hereditary spherocytosis are similar to those of various hemolytic anemias, which causes hereditary spherocytosis to be difficult to diagnose clinically. In this case, we obtained the peripheral blood of a patient and family members, and through a whole exome test of the 6,297 genetic phenotypes confirmed by OMIM, we found a heterozygous nonsense mutation (c.4117C>T, P.Q1373X) in the SPTB gene. Combined with the patient's clinical data, the diagnosis was hereditary spherocytosis. Compared with the public population sequence database, the mutation was found to be unique. Through protein structure prediction analysis and literature studies, we found that the mutation may cause SPTB mRNA instability, resulting in insufficient spectrin protein synthesis and affecting the integrity and flexibility of the red blood cell membrane skeleton. This case report found that SPTB gene mutations may cause liver dysfunction and cirrhosis in addition to hereditary spherocytosis, and this finding expands the phenotypic spectrum of SPTB. This study confirmed that NGS can be used to diagnose hereditary spherocytosis. Identifying mutated genes can not only accurately treat diseases, but also avoid potential genetic risks and improve prenatal and postnatal care.
PubMed: 35223921
DOI: 10.3389/fmed.2022.823724 -
Canadian Medical Association Journal Jan 1956
Topics: Anemia, Hemolytic, Congenital; Ankyrins; Humans; Jaundice; Spherocytosis, Hereditary
PubMed: 13276901
DOI: No ID Found -
American Journal of Hematology Jun 2020
Topics: Aged; Erythropoiesis; Humans; Male; Spherocytosis, Hereditary
PubMed: 32020666
DOI: 10.1002/ajh.25747 -
American Journal of Hematology Jan 1998Thrombocytosis in post-splenectomy patients with hereditary spherocytosis (HS) is usually not attended by an increased risk of thrombosis. Review of the literature... (Review)
Review
Thrombocytosis in post-splenectomy patients with hereditary spherocytosis (HS) is usually not attended by an increased risk of thrombosis. Review of the literature revealed HS in association with pulmonary thrombosis, portal vein thrombosis, and cerebral infarction in two brothers, TTP in an asplenic patient and a patient with corpora cavernosum thrombosis causing segmental priapism. We report a case of a 30-year-old white male with HS who presented with hemoptysis 29 years after splenectomy. Work-up revealed a hypercoagulable state with thrombocytosis and recurrent pulmonary emboli resulting in severe pulmonary hypertension, cor pulmonale, atrial flutter, and syncope.
Topics: Adult; Chronic Disease; Humans; Male; Pulmonary Embolism; Spherocytosis, Hereditary; Splenectomy; Thrombocytosis
PubMed: 9423823
DOI: 10.1002/(sici)1096-8652(199801)57:1<82::aid-ajh15>3.0.co;2-b -
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 -
Nefrologia 2020Hereditary spherocytosis is clinically and genetically heterogeneous disorder and its clinical characteristics are spherocytosis, anaemia, jaundice and splenomegaly. The...
BACKGROUND
Hereditary spherocytosis is clinically and genetically heterogeneous disorder and its clinical characteristics are spherocytosis, anaemia, jaundice and splenomegaly. The aetiology is associated to the genes encoding proteins involved in the interaction between the erythrocyte membrane and the lipid bilayer. Causative variants in βI-spectrin (SPTB) gene presenting as mild to moderately severe disease are responsible for approximately 25% cases in the USA and Europe. Among kidney disease, isolated cases of nephrotic syndrome due to membranoproliferative glomerulonephritis and macroscopic haematuria with proteinuria due to IgA nephropathy were previously reported in patients with SPTB deficiency.
OBJECTIVE
Seven patients from the same family with spherocytosis were evaluated to assess the kidney failure presented in all affected adult patients.
METHODS
Clinical, radiological and laboratory investigations were issued to evaluate the spherocytosis and kidney disease. In selected patients, we also performed genetics testing with next generation sequencing of genes related to hereditary spherocytosis, inherited glomerular disorders and tubulo-interstitial kidney disease.
RESULTS
Among the family members with spherocytosis, two adults had end-stage kidney disease and one chronic kidney disease stage 4 with unspecific histopathological findings of interstitial fibrosis/tubular atrophy and glomerulosclerosis. At the time, there were no signs of kidney disease present in four paediatric patients. Novel nonsense variant in SPTB gene (NM_001024858; c.4796G>A; p.Trp1599Ter) was detected in all family members with spherocytosis and was predicted to be disease causing. Furthermore, all adult patients with kidney failure and two paediatric cousins of the index patients were heterozygous for the UMOD gene variant (NM_003361.3:c.552G>C, NP_003352.2:p.Trp184Cys) previously reported in patients with tubulo-interstitial kidney disease. UMOD variant was not present in the index patients.
CONCLUSIONS
The co-occurrence of any two rare inherited disorders is extremely rare, while to our knowledge the co-occurrence of genetically confirmed HS and autosomal dominant tubulo-interstitial kidney disease (ADTKD) has previously not been reported. It is not possibly to evaluate whether the haemolytic crises due to HS are influencing the progression of the UMOD related renal disease, since the UMOD related ADTKD characteristics in general and in here presented family are extremely variable. Nevertheless, the observed kidney disease in the family is warranting the regular nephrological examinations in UMOD positive paediatric patients in the family in order to recognise hyperuricemia and treat it as early as possible. This is emphasising the importance of serum uric acid detection in routine laboratory screening of paediatric patients in order to identify early signs of tubular injury indicating possible ADTKD.
Topics: Female; Humans; Kidney Failure, Chronic; Male; Pedigree; Spectrin; Spherocytosis, Hereditary; Uromodulin
PubMed: 32113667
DOI: 10.1016/j.nefro.2019.10.009 -
Haematologica 2020Hereditary spherocytosis (HS) originates from defective anchoring of the cytoskeletal network to the transmembrane protein complexes of the red blood cell (RBC). Red...
Hereditary spherocytosis (HS) originates from defective anchoring of the cytoskeletal network to the transmembrane protein complexes of the red blood cell (RBC). Red cells in HS are characterized by membrane instability and reduced deformability and there is marked heterogeneity in disease severity among patients. To unravel this variability in disease severity, we analyzed blood samples from 21 HS patients with defects in ankyrin, band 3, α-spectrin or β-spectrin using red cell indices, eosin-5-maleimide binding, microscopy, the osmotic fragility test, Percoll density gradients, vesiculation and ektacytometry to assess cell membrane stability, cellular density and deformability. Reticulocyte counts, CD71 abundance, band 4.1 a:b ratio, and glycated hemoglobin were used as markers of RBC turnover. We observed that patients with moderate/severe spherocytosis have short-living erythrocytes of low density and abnormally high intercellular heterogeneity. These cells show a prominent decrease in membrane stability and deformability and, as a consequence, are quickly removed from the circulation by the spleen. In contrast, in mild spherocytosis less pronounced reduction in deformability results in prolonged RBC lifespan and, hence, cells are subject to progressive loss of membrane. RBC from patients with mild spherocytosis thus become denser before they are taken up by the spleen. Based on our findings, we conclude that RBC membrane loss, cellular heterogeneity and density are strong markers of clinical severity in spherocytosis.
Topics: Ankyrins; Erythrocyte Membrane; Erythrocytes; Humans; Reticulocyte Count; Spherocytosis, Hereditary
PubMed: 31147440
DOI: 10.3324/haematol.2018.188151 -
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