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Experimental and Therapeutic Medicine Sep 2022Hereditary spherocytosis (HS) is an erythrocyte membrane disease with a non-specific phenotype, particularly occurring in neonatal patients, and its diagnosis is...
Hereditary spherocytosis (HS) is an erythrocyte membrane disease with a non-specific phenotype, particularly occurring in neonatal patients, and its diagnosis is challenging. The present study reports on a patient with neonatal HS and reviewed the genetic characteristics of reported neonatal HS cases in China. The patient was admitted only a few hours after birth with jaundice. Auxiliary examination indicated anemia and hyperbilirubinemia. Spherical erythrocytes were occasionally observed in peripheral blood smears. Genetic testing suggested that the patient harbored a novel frameshift mutation (p.Asp495fsTer78) in spectrum, β, erythrocytic (SPTB), which was carried by the father. Review of 160 cases of HS in China revealed 24 to be neonatal cases. In these neonatal cases, the frequency of ankyrin 1 (ANK1) mutations and loss-of-function mutations of pathogenic genes (including ANK1 and SPTB) was higher than that in the non-neonatal group. In conclusion, the present study further expanded the mutation spectrum of SPTB and reaffirms the diagnostic value of gene detection in neonatal HS.
PubMed: 35949318
DOI: 10.3892/etm.2022.11537 -
Eye (London, England) Jun 2023To assess systemic associations of angioid streaks (AS) using a large US healthcare database.
BACKGROUND/OBJECTIVES
To assess systemic associations of angioid streaks (AS) using a large US healthcare database.
SUBJECTS/METHODS
A retrospective cross-sectional study was conducted of patients diagnosed with AS in a large, national US insurer from 2000-2019. Cases were matched 1:5 to controls. The prevalence rates of established associated disease states and other systemic diseases were calculated and compared using logistic regression. Additionally, the rate of anti-VEGF treatment was assessed as a proxy for the incidence of choroidal neovascularization (CNV).
RESULTS
One thousand eight hundred fifty-two cases of AS and 9028 matched controls were included. The rates of association between AS and the well-characterized conditions included: Pseudoxanthoma elasticum (PXE)-228 patients (12.3%), Ehlers-Danlos syndrome-18 patients (1.0%), Paget's disease-6 patients (0.3%), hemoglobinopathies-30 patients (1.6%), and idiopathic-1573 patients (84.9%). There was a statistically higher prevalence of the following less classically associated diseases among patients with AS compared to controls: hereditary spherocytosis (1.7% vs. 0.6%, p < 0.001), connective tissue disease (1.0% vs 0.3%, p < 0.001) and non-exudative age-related macular degeneration (33.9% vs 10.6%, p < 0.001). Among 1442 eligible cases analyzed, 427 (29.6%) received at least 1 anti-VEGF injection with 338 (23.4%) patients having the injection after their AS diagnosis.
CONCLUSIONS
In the largest collection of AS patients to date, the classical teaching of systemic disease associations occur at rates far, far lower than previously reported. The association of AS with other less reported diseases highlights new potential associations and may contribute to the understanding of AS formation.
Topics: Humans; Angioid Streaks; Retrospective Studies; Cross-Sectional Studies; Pseudoxanthoma Elasticum; Choroidal Neovascularization; Delivery of Health Care; Fluorescein Angiography
PubMed: 35915234
DOI: 10.1038/s41433-022-02189-x -
Frontiers in Physiology 2022Hereditary spherocytosis is a common red blood cell disease caused by an inherited red blood cell membrane defect, leading to a spherical shape and propensity for...
Hereditary spherocytosis is a common red blood cell disease caused by an inherited red blood cell membrane defect, leading to a spherical shape and propensity for hemolysis. There is a lack of reports on intraoperative autologous blood transfusion for hereditary spherocytosis patients. We hereby report our recent experience with using the Cell Saver system for intraoperative red blood cell salvage on a hereditary spherocytosis patient. There was a drastic increase in salvaged blood free-hemoglobin compared with the preoperative sample (82.6 mg/dl vs. 6.2 mg/dl) which indicated severe hemolysis. Although our patient recovered smoothly with a normal liver and renal function test and reported no adverse reaction during follow-up, it is noteworthy that severe hemolysis could happen during the cell salvage process for patients with hemolytic anemia, as there are similar reports on sickle cell anemia, beta-thalassemia intermedia, and paroxysmal nocturnal hemoglobinuria. Therefore, more clinical attention and thorough research should be drawn into this perspective, namely, hemolysis during the red blood cell salvage process for patients with hemolytic anemia.
PubMed: 35846021
DOI: 10.3389/fphys.2022.926398 -
EJHaem Nov 2021The eosin-5'-maleimide (EMA) binding test is widely used as diagnostic test for hereditary spherocytosis (HS), one of the most common haemolytic disorders in Caucasian...
The eosin-5'-maleimide (EMA) binding test is widely used as diagnostic test for hereditary spherocytosis (HS), one of the most common haemolytic disorders in Caucasian populations. We recently described the advantages of replacing the use of healthy control blood samples with fluorescent beads in a modified EMA binding assay. In this study we further explore this novel approach. We performed targeted next-generation sequencing, modified EMA binding test and osmotic gradient ektacytometry on consecutive individuals referred to our laboratory on the suspicion of HS. In total, 33 of 95 carried a (likely) pathogenic variant, and 24 had variants of uncertain significance (VUS). We identified a total 79 different (likely) pathogenic variants and VUS, including 43 novel mutations. Discarding VUS and recessive mutations in , we used the occurrence of (likely) pathogenic variants to generate a diagnostic threshold for our modified EMA binding test. Twenty-one of 23 individuals with non- (likely) pathogenic variants had EMA ≥ 43.6 AU, which was the optimal threshold in receiver operating characteristic (ROC) analysis. Accuracy was excellent at 93.4% and close to that of osmotic gradient ektacytometry (98.7%). In conclusion, we were able to simplify the EMA-binding test by using rainbow beads as reference and (likely) pathogenic variants to define an accurate cut-off value.
PubMed: 35845192
DOI: 10.1002/jha2.277 -
American Journal of Hematology Oct 2022
Topics: Anemia, Hemolytic, Congenital; Elliptocytosis, Hereditary; Humans; Spectrin; Spherocytosis, Hereditary
PubMed: 35834292
DOI: 10.1002/ajh.26662 -
Respirology Case Reports Aug 2022A 32-year-old patient, who was on treatment for tuberculous meningitis complicated with venous sinus thrombosis, was referred to the medical unit as he developed new...
A 32-year-old patient, who was on treatment for tuberculous meningitis complicated with venous sinus thrombosis, was referred to the medical unit as he developed new onset fever, cough and shortness of breath. He was in respiratory distress and needed intubation. Investigations revealed elevated liver enzymes, leukopenia, spherocytosis and lower lobe predominant consolidations and diffuse nodules in the high-resolution computed tomography. He was suspected to have cytomegalovirus (CMV) pneumonia with the above results, and further investigations revealed an extremely elevated CMV viral load. He was treated with ganciclovir followed by valganciclovir for a total of 42 days resulting in a complete recovery. Liver functions resolved with anti-viral treatment, and he was started on full anti-tuberculosis (TB) treatment. Further investigations did not reveal evidence of immunosuppression. Association of CMV and TB is explained genetically, although clinical association is rarely described. The presence of either infection should lead to higher degree of suspicion of the respective other condition in relevant clinical setting.
PubMed: 35832322
DOI: 10.1002/rcr2.1002 -
World Journal of Clinical Cases May 2022Hereditary spherocytosis (HS) is characterized by anemia, jaundice, splenomegaly, and cholelithiasis, and is caused by abnormal genes encoding red blood cell membrane...
BACKGROUND
Hereditary spherocytosis (HS) is characterized by anemia, jaundice, splenomegaly, and cholelithiasis, and is caused by abnormal genes encoding red blood cell membrane components. The most common mutations found in HS are in the gene.
CASE SUMMARY
A 4-mo-old girl was admitted to our hospital with pallor that had lasted for more than 2 mo. She presented with jaundice, anemia and splenomegaly. A heterozygous mutation of (exon23: c.G2467T:p.E823X) was identified, and the mutation was determined to be autosomal dominant. This mutation is linked to the relatively serious anemia she had after birth; this anemia improved with age.
CONCLUSION
The utilization of next-generation sequencing may assist with the accurate diagnosis of HS, especially in atypical cases.
PubMed: 35801015
DOI: 10.12998/wjcc.v10.i15.4923 -
Leukemia Research Reports 2022Hereditary spherocytosis (HS) is the most prevalent red blood cell (RBC) membrane disorder. We report a rare case of acquired spherocytosis coinciding with a...
Hereditary spherocytosis (HS) is the most prevalent red blood cell (RBC) membrane disorder. We report a rare case of acquired spherocytosis coinciding with a myelodysplastic syndrome associated mutation, neither found in germline DNA. The diagnosis was confirmed by Eosin-5-Maleimide binding assay and Next Generation Sequencing (NGS). The patient recovered quickly after splenectomy, which confirms that his myelodysplastic syndrome (MDS)-associated mutation did not affect the clinical picture. This case highlights the essence of thoroughly examining the etiology of hemolytic indices, despite bone marrow morphology and myeloid gene panel supporting a diagnosis of MDS with single line dysplasia.
PubMed: 35720514
DOI: 10.1016/j.lrr.2022.100332 -
Cancers May 2022Alectinib is a standard initial treatment for patients with advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). The current study...
Alectinib is a standard initial treatment for patients with advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). The current study analyzed a prospective cohort of 24 consecutive alectinib-treated patients and controls in order to comprehensively characterize longitudinal erythrocyte changes under treatment with ALK inhibitors. Upon starting alectinib, all examined patients developed reticulocytosis and abnormal erythrocyte morphology with anisocytosis and a predominance of acanthocytes (64% of red blood cells on average, range 36−100%) in the peripheral blood smear within approximately 2 weeks. Changes were accompanied by a gradual reduction in Eosin-5-maleimide (EMA) binding, which became pathologic (<80% of cells) within 1−2 months in all cases, mimicking an abortive form of hereditary spherocytosis. The latter could be ruled out in 3/3 of analyzed cases by normal sequencing results for the ANK1, EPB42, SLC4A1, SPTA1, or SBTB genes. The direct Coombs test was also negative in 11/11 tested cases. Besides, anemia, increased LDH, and increased bilirubin were noted in a fraction of patients only, ranging between 42 and 68%. Furthermore, haptoglobin decreases were infrequent, occurring in approximately 1/3 of cases only, and mild, with an average value of 0.93 g/L within the normal range of 0.3−2 g/dL, suggesting that hemolysis occurred predominantly in the extravascular compartment, likely due to splenic trapping of the deformed erythrocytes. These changes showed no association with progression-free survival under alectinib or molecular features, i.e., ALK fusion variant or TP53 status of the disease, and resolved upon a switch to an alternative ALK inhibitor. Thus, alectinib induces mild, reversible erythrocyte changes in practically all treated patients, whose most sensitive signs are aberrant red cell morphology in the peripheral smear, a pathologic EMA test, and reactive reticulocytosis. Frank hemolytic anemia is rare, but mild subclinical hemolysis is very frequent and poses differential-diagnostic problems. Alectinib can be continued under the regular control of hemolysis parameters, but the risk of long-term complications, such as cholelithiasis due to increased serum bilirubin in most patients, remains unclear at present.
PubMed: 35681698
DOI: 10.3390/cancers14112720 -
BMC Medical Genomics Jun 2022The deletion of a short arm fragment on chromosome 8 is a rare cause of Kallmann syndrome and spherocytosis due to deletion of the FGFR1 and ANK1 genes.
BACKGROUND
The deletion of a short arm fragment on chromosome 8 is a rare cause of Kallmann syndrome and spherocytosis due to deletion of the FGFR1 and ANK1 genes.
CASE PRESENTATION
This case study describes a 4-month-old child with growth and psychomotor retardation, auricle deformity, microcephaly, polydactyly, a heart abnormality, and feeding difficulties. An approximately 12.00 MB deletion was detected in the 8p11.22-p21.2 region of chromosome 8. After sequencing, we found that 65 protein genes had been deleted, including FGFR1, which resulted in Kallmann syndrome. There was no deletion of the ANK1 gene associated with spherocytosis, consistent with the phenotype.
CONCLUSION
This patient is a new case of short arm deletion of chromosome 8, resulting in novel and previously unreported clinical features.
Topics: Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 22; Humans; Kallmann Syndrome; Spherocytosis, Hereditary
PubMed: 35668409
DOI: 10.1186/s12920-022-01274-0