Severe Hemolytic Anemia Research Articles

Outcomes of therapeutic plasma exchange in severe autoimmune hemolytic anemia hospitalizations: An analysis of the National Inpatient Sample.

Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear. We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not. We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001). Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes.

Babesia gibsoni Infection in a Cat with Immune-Mediated Haemolytic Anaemia and Thrombocytopenia

Tick-borne haemoparasite Babesia gibsoni has been detected rarely in cats, in surveys of apparently healthy animals. In stored blood from a 6-year-old male-neutered domestic shorthair cat in Hong Kong, B. gibsoni DNA was detected retrospectively using PCR for Babesia spp. 18S rRNA and mitochondrial cytochrome B genes, followed by sequencing and basic local alignment search tool (BLAST) analysis. The cat presented with severe haemolytic anaemia and thrombocytopenia. The cat responded to supportive care and glucocorticoids and was clinically normal despite persistent subclinical thrombocytopenia until six months after presentation, when it succumbed to a fatal haemorrhagic episode. Necropsy revealed severe intestinal and pulmonary haemorrhage and hypocellular bone marrow with megakaryocytosis but no other causes of immune-mediated thrombocytopenia (IMTP) or immune-mediated haemolytic anaemia (IMHA). Blood stored on days 158 and 180 tested PCR negative for Babesia spp. This report demonstrates that geographic range of B. gibsoni detection in cats includes Hong Kong. The exclusion of other causes suggests that B. gibsoni might have potentially played a role in triggering immune-mediated disease in this case.

A Case of Compound Heterozygous HbS and HbD Disease in Premarital Screening

Introduction: Among the inherited disorders of blood, haemoglobinopathy and thalassaemia constitute a major bulk of non-communicable genetic diseases in India. They cause a high degree of morbidity in affected individuals. Moderate to severe haemolytic anaemia among vulnerable segments of the society like infants and children, adolescent girls, pregnant women, etc. may result in many deaths in India. Hemoglobinopathies are a vast group of inherited disorders of hemoglobin production and function. Compound heterozygous HbSD-Punjab is an uncommon hemoglobinopathy encountered in Indians. In premarital screening, molecular testing is mostly inconvenient and diagnosis often relies on the abnormal hemoglobin analysis, family studies and epidemiological facts. We present the clinical and laboratory characteristics of hemoglobin D-Punjab with sickle cell disease found on premarital screening. Case Report: Blood sample of a 22 year old patient for high-performance liquid chromatography was received. A complete blood count (CBC) showed mild anemia with Hb of 8.3 g/dl with mild microcytic hypochromic red cell indices.The HPLC showed HbD and S-window on BIO RAD D10 machine. The high-performance liquid chromatography showed normal hemoglobin Hb F and Hb A2, which indicates presence of a Compound heterozygous for HbSD-Punjab. Conclusion: Compound heterozygous state for HbD-Punjab with S-window is a rare disorder. HbSD-Punjab has a heterogeneous clinical presentation. Anemia and sickle crises are quite common. The data obtained from the clinical findings, blood picture and electrophoresis or HPLC will help in diagnosis. Genetic counseling is advisable in patients with presence of a Compound heterozygous HbSD-Punjab.

Piperacillin-tazobactam induced immune hemolytic anemia led to increased renal impairment and eventual death from multiple organ failure in a patient with hypertensive nephropathy: case report and literature review

BackgroundPiperacillin is one of the most common drugs that cause drug-induced immune hemolytic anemia, but a complete description of the serological features and course of the disease is rare. This study completely describes the serological characteristics and course of a patient with hypertensive nephropathy who developed drug-induced immune hemolytic anemia and worsened renal function during repeated administration of piperacillin-tazobactam.Case presentationA 79-year-old male patient with hypertensive nephropathy who developed severe hemolytic anemia and worsened renal function during intravenous piperacillin-tazobactam anti-infective treatment due to lung infection. Serological tests showed that the result of the direct antiglobulin test for anti-IgG was positive (4 +) and anti-C3d was negative, and the irregular red blood cell antibody screening test was negative. Plasma samples collected at different times from 2 days before to 12 days after the discontinuation of piperacillin-tazobactam administration were incubated with piperacillin solution and red blood cells of O-type healthy blood donors at 37 °C, IgG piperacillin-dependent antibodies were detected, and the highest titer was 128. However, no tazobactam-dependent antibody was detected in any plasma samples. Therefore, the patient was diagnosed with piperacillin-induced immune hemolytic anemia. Although blood transfusion and continuous renal replacement therapy were given, the patient died of multiple organ failure 15 days after the administration of piperacillin-tazobactam was stopped.ConclusionThis is the first complete description of the disease course and serological changes of piperacillin-induced immune hemolytic anemia, which is bound to help deepen the understanding of drug-induced immune hemolytic anemia and draw profound lessons from it.

Severe autoimmune intravascular hemolytic anemia in patients receiving alemtuzumab for multiple sclerosis.

Severe autoimmune intravascular hemolytic anemia in patients receiving alemtuzumab for multiple sclerosis.

Spur cells in liver cirrhosis are predictive of acute-on-chronic liver failure and liver-related mortality regardless of severe anaemia.

Chronic anaemia in advanced liver disease is a frequent finding. The aim was to explore the clinical impact of spur cell anaemia, a rare entity typically associated with end-stage of the disease. One-hundred and nineteen patients (73.9% males) with liver cirrhosis of any etiology were included. Patients with bone marrow diseases, nutrients deficiencies and hepatocellular carcinoma were excluded. In all patients, a blood sample was collected to check for the presence of spur cells on blood smear. A complete blood biochemical panel was recorded together with Child-Pugh (CP) score and Model for End-Stage Liver Disease (MELD) score. For each patients, clinically relevant events, such as acute-on-chronic liver failure (ACLF) and 1year liver-related mortality, were registered. Patients were then grouped according to the percentage of spur cells at smear (> 5%, 1-5%, < 1%). Severe anaemia was defined as haemoglobin levels lower than 8g/dL. 9.2% of subjects had > 5% spur cells, only 2 had evidence of haemolysis. In patients with > 5% spur cells, haemoglobin and albumin were lower compared with the other sub-group, while MELD score, CP score, International Normalized Ratio, ferritin, creatinine and unconjugated bilirubin were higher. Patients with more spur cells were more decompensated and developed more frequently ACLF. ACLF and liver-related mortality were significantly and independently associated with the presence of > 5% spur cells but not with baseline severe anaemia. Cirrhotic patients have a fairly high prevalence of spur cells, not always associated with severe haemolytic anaemia. The presence of spur red cells is per se associated with a worse prognosis and, therefore, should be always evaluated to prioritize patients for intensive management and eventually liver transplantation.

Diagnostic and Treatment Challenges in a Pediatric Patient with Progressive Refractory ALPS-like Disease

Introduction: Diagnostic criteria for Autoimmune Lymphoproliferative Syndrome (ALPS) is based on clinical, laboratory and genetic findings. The underlying pathomechanisms are largely related to defects in the lymphocyte apoptosis pathways (FAS, FAS ligand, or CASP10) but other combined immunodeficiencies may also present with ALPS-like features (e.g. CASP8, NFKB1, CTLA4, ALP1). Clinically, patients often present with progressive autoimmune cytopenias and treatment relies on T cell immune modulation. Hereby, we present diagnostic and treatment challenges in a pediatric patient with ALPS-like phenotype with rapid decline during an episode of severe autoimmune hemolytic anemia. MethodsRetrospective chart review for clinical and laboratory data. Deep immune phenotyping was obtained for T, B and NK cells subsets at several timepoints during the acute illness. Genetic evaluation for both germline and somatic mutations were pursued.Case presentation: Patient is an 11-year-old Syrian male of consanguineous parents who presented at age 6 with immune thrombocytopenic purpura (ITP) and met criteria for ALPS with required criteria (chronic lymphadenopathy and increased T Cell Receptor αβ CD4-CD8- double negative T cells (TCRαβDNT) (4.2%, normal <2%), primary accessory criteria (defective lymphocyte apoptosis twice) and secondary accessory criteria (elevated B12, IgG and FAS-L). Panel sequencing (207 genes of inborn errors of immunity) and later Whole Exome Sequencing were both unrevealing. At 11 years of age, he was admitted with a Coombs positive severe autoimmune hemolytic anemia (hemoglobin of 3.5) that was complicated by EBV and parvovirus viremia, and aplastic anemia. Treatment course was complex including steroid, high dose IvIg, rituximab, sirolimus, mycophenolate mofetil, eculizumab, and epoetin alpha. Biomarkers of immune dysregulation, such as TCRαβDNT, follicular helper T cells and CD19hiCD21lo B cells were monitored closely and improved on therapy. Total T cell, CD4, CD8, and Treg populations were all initially low but returned to baseline following combined treatment. Screening for somatic mutations and whole genome sequencing is ongoing. Discussion/ConclusionOur case highlights the diagnostic and treatment challenges in a pediatric patient with ALPS-like Disease. Cellular biomarkers may guide therapy if autoimmune cytopenia recurs. Somatic and germline testing is needed to understand the underpinning of this disorder and may further guide treatment strategies.

Paediatric autoimmune diseases with ELANE mutations associated with neutropenia

ObjectiveTo explore the clinical characteristics of autoimmune diseases in children with ELANE mutations.MethodsThree cases of children with ELANE mutations manifesting as autoimmune diseases, who were under treatment from April 2020 to May 2021, were retrospectively analysed.ResultsAmong the three children, two were boys aged 15 years and 22 months (cases 1 and 3) respectively, and the other one was a 22-month-old girl (case 2). All the cases had recurrent infections. Case 1 presented with cyclic neutropenia and systemic lupus erythematosus (SLE). Case 2 presented with severe neutropenia and autoimmune haemolytic anaemia (AHIA). Case 3 presented with severe neutropenia and anti-neutrophil cytoplasm antibodies (ANCA)-associated small vasculitis. Genetic tests showed that they all had heterozygous mutations in the ELANE gene. Case 1 was treated with methylprednisolone and hydroxychloroquine sulphate for 2 years, making neutrophil level return to normal. Case 2 received allogeneic hematopoietic stem cell transplantation and has stopped taking antibiotics, steroids and all the immunosuppressors. Case 3 received subcutaneous injections of granulocyte colony-stimulating factor, oral prednisone and cyclophosphamide. The boy in case 3 has been followed up for one year, and his absolute neutrophil count has increased to 1.56 × 109/L.ConclusionPatients with ELANE mutations, combined with autoimmune diseases, may have recurrent infections. Disease-modifying antirheumatic drugs (DMARDs) are effective for autoimmune diseases. Autoimmune diseases with ELANE mutations associated with neutropenia can be cured through allogeneic hematopoietic stem cell transplantation.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Predictors of severe hemolytic anemia and its impact on major outcomes in systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

To determine the predictors of the occurrence of severe autoimmune hemolytic anemia (AIHA) and its impact on damage accrual and mortality in SLE patients. Factors associated with time to severe AIHA (hemoglobin level ≤7g/dL) occurring from the onset of SLE symptoms were examined by Cox proportional hazards regressions. The association of severe AIHA with mortality was examined by logistic regression analyses while its impact on damage was by negative binomial regression. Of 1,349 patients, 49 (3.6%) developed severe AIHA over a mean (SD) follow-up time of 5.4 (3.8) years. The median time from the first clinical manifestation to severe AIHA was 111days (IQR 43-450). By multivariable analysis, male sex (HR 2.26, 95% CI 1.02-4.75, p = 0.044), and higher disease activity at diagnosis (HR 1.04, 95% CI 1.01-1.08, p = 0.025) were associated with a shorter time to severe AIHA occurrence. Of the SLEDAI descriptors, only hematologic (leukopenia and/or thrombocytopenia) showed a certain trend toward significance in the multivariable analysis (HR 2.36, 95% CI 0.91-6.13, p = 0.0772). Severe AIHA contributed neither to damage nor to mortality. Severe AIHA occurs during the early course of SLE. Male sex and higher disease activity at diagnosis emerged as independent predictors of a shorter time to severe AIHA occurrence. Although not statistically significant, hematological abnormalities at SLE diagnosis could predict the occurrence of severe AIHA in a shorter time. Damage and mortality did not seem to be impacted by the occurrence of severe AIHA.

Severe Hemolytic Anemia and Metabolic Acidosis at Birth with Glutathione Synthetase Deficiency and Progressive Neurological Symptoms on Follow-Up.

BACKGROUND Glutathione synthetase deficiency (GSD) is a rare autosomal recessive disorder caused by glutathione synthetase (GSS) gene variants that occur in 1 in 1 million individuals. The severe form of GSD is characterized by hemolytic anemia, metabolic acidosis with 5-oxoprolinuria, progressive neurological symptoms, and recurrent bacterial infections. This case report presents a male Japanese infant with severe hemolytic anemia and metabolic acidosis at birth caused by GSD, who developed progressive neurological symptoms on follow-up. CASE REPORT A Japanese male term infant developed severe hemolytic anemia and metabolic acidosis in the early neonatal period. We suspected GSD based on his symptoms and a high 5-oxoproline urine concentration. We began correcting his metabolic acidosis and administering vitamins C and E supplements. The patient required blood transfusion twice during the acute phase for hemolytic anemia. After age 1 month, he maintained good control of metabolic acidosis and hemolytic anemia. A definitive diagnosis of GSD was made based on high concentrations of 5-oxoproline in urine, low concentrations of glutathione and GSS activity in erythrocytes, and genetic testing. Several episodes of febrile convulsions were started at age 11 months, but none occurred after 2 years. At the last follow-up at age 25 months, metabolic acidosis and hemolytic anemia were well controlled, but he had mild neurodevelopmental delay. CONCLUSIONS This case report shows that GSD can present with severe hemolytic anemia and metabolic acidosis at birth, and manifest with subsequent neurological impairment despite early diagnosis and treatment. Therefore, a careful long-term follow-up that includes neurological evaluation is essential for patients with GSD.

Case Report] Challenging Detection of Latent Tuberculosis in a Patient Undergoing High-Dose Corticosteroid Therapy for Acute Hemolytic Anemia and Rhupus Arthropathy

Acute autoimmune hemolytic anemia requires rapid stabilization, typically through the administration of high-dose corticosteroids. However, it is important to consider reactivation of latent infection and how immune suppression can interfere with molecular screening tools. In this case report, we present a patient with Rheumatoid Arthritis/Systemic Lupus Erythematosus experiencing severe autoimmune hemolytic anemia complicated by an unknown latent tuberculosis infection.

Targeted next-generation sequencing identifies eighteen novel mutations expanding the molecular and clinical spectrum of PKLR gene disorders in the Indian population.

Pyruvate kinase deficiency (PKD) is an autosomal recessive condition, caused due to homozygous or compound heterozygous mutation in the PKLR gene resulting in non-spherocytic hereditary hemolytic anemia. Clinical manifestations in PKD patients vary from moderate to severe lifelong hemolytic anemia either requiring neonatal exchange transfusion or blood transfusion support. Measuring PK enzyme activity is the gold standard approach for diagnosis but residual activity must be related to the increased reticulocyte count. The confirmatory diagnosis is provided by PKLR gene sequencing by conventional as well as targeted next-generation sequencing involving genes associated with enzymopathies, membranopathies, hemoglobinopathies, and bone marrow failure disorders. In this study, we report the mutational landscape of 45 unrelated PK deficiency cases from India. The genetic sequencing of PKLR revealed 40 variants comprising 34 Missense Mutations (MM), 2 Nonsense Mutations (NM), 1 Splice site, 1 Intronic, 1 Insertion, and 1 Large Base Deletion. The 17 novel variants identified in this study are A115E, R116P, A423G, K313I, E315G, E318K, L327P, M377L, A423E, R449G, H507Q, E538K, G563S, c.507 + 1 G > C, c.801_802 ins A (p.Asp268ArgfsTer48), IVS9dsA-T + 3, and one large base deletion. In combination with previous reports on PK deficiency, we suggest c.880G > A, c.943G > A, c.994G > A, c.1456C > T, c.1529G > A are the most frequently observed mutations in India. This study expands the phenotypic and molecular spectrum of PKLR gene disorders and also emphasizes the importance of combining both targeted next-generation sequencing with bioinformatics analysis and detailed clinical evaluation to elaborate a more accurate diagnosis and correct diagnosis for transfusion dependant hemolytic anemia in a cohort of the Indian population.

Clinical utility of targeted next-generation sequencing panel in routine diagnosis of hereditary hemolytic anemia: A national reference laboratory experience.

Hereditary hemolytic anemias (HHA) comprise a heterogeneous group of disorders resulting from defective red blood cell (RBC) cytoskeleton, RBC enzyme deficiencies, and hemoglobin (Hb) synthesis disorders such as thalassemia or sideroblastic anemia. Our hemolytic anemia diagnostic next-generation sequencing (NGS) panel includes 28 genes encoding RBC cytoskeletal proteins, membrane transporter, RBC enzymes, and certain bilirubin metabolism genes. The panel covers the complete coding region of these genes, splice junctions, and, wherever appropriate, deep intronic or regulatory regions are also included. Four hundred fifty-six patients with unexplained hemolytic anemia were evaluated using our NGS panel between 2015 and 2019. We identified pathogenic/likely pathogenic variants in 111/456 (24%) patients that were responsible for the disease phenotype (e.g., moderate to severe hemolytic anemia and hyperbilirubinemia). Approximately 40% of the mutations were novel. As expected, 45/456 (10%) patients were homozygous for the promoter polymorphism in the UGT1A1 gene, A(TA)7 TAA (UGT1A1*28). 8/45 homozygous UGT1A1*28 cases were associated with additional pathogenic mutations causing hemolytic anemia, likely exacerbating hyperbilirubinemia. The most common mutated genes were membrane cytoskeleton genes SPTA1, and SPTB, followed by PKLR. Complex interactions between SPTA1 low expression alleles, alpha-LELY and alpha-LEPRA alleles, and intragenic SPTA1 variants were associated with hereditary pyropoikilocytosis and autosomal recessive hereditary spherocytosis in 23/111 patients. Our results demonstrate that hemolytic anemia is underscored by complex molecular interactions of previously known and novel mutations in RBC cytoskeleton/enzyme genes, and therefore, NGS should be considered in all patients with clinically unexplained hemolytic anemia and in neonates with hyperbilirubinemia. Moreover, low expression alleles alpha-LELY and alpha-LEPRA should be included in all targeted HHA panels.

Iron Status in Sickle Cell Anemia: Deficiency or Overload?

Background Sickle cell anemia (SCA) is a hereditary disease with defective hemoglobin (Hb) synthesis causing severe hemolytic anemia, pain crisis, and target organ damage. In SCA, several factors independently or in combination lead to derangement in iron stores. Some centers incorrectly prescribe iron therapy on the presumption that SCA would be associated with iron deficiency, but it is not always the case. This study attempts to evaluate the iron status in SCA patients and records the target organ damage present. Methodology A single-center cross-sectional study of 180 patients with sickle cell disease was carried out at a tertiary-care center in Western India. Patients >12 years of age were included in the study after confirming SCA using high-performance liquid chromatography (HPLC). The iron status of each patient was identified and patients were labeled as iron sufficient based on the following values: Hb (8.1-12 gm%), serum iron (S. iron) level (50-150 μg/dl), serum ferritin (S. ferritin) (50-200 ng/ml), and total iron binding capacity (TIBC) (251-450 µg/dl). The iron status of patients with different target organ damage was also analyzed. Results Demographic data revealed that 21-30 years was the most common age group affected by SCA along with a male preponderance. The most common presenting complaint was joint pain (68.9%), the most common sign was pallor (64.4%), most patients had a history of pain crisis (95.6%), and half of the patients had organomegaly (51.1%). Most of the patients had no complications, however, for those who did, hepatopathy (28.9%) was the most common. Conclusion While the majority of patients were iron sufficient, a considerable number had either iron deficiency or iron overload states, which emphasizes the necessity of investigating the iron status before deciding the course of treatment in SCA patients. Although the majority were unaffected, screening for end-organ damage should be carried out in all SCA patients.

High prevalence and genetic diversity of hemoplasmas in bats and bat ectoparasites from China

Hemoplasmas can cause severe hemolytic anemia in humans. To explore the genetic diversity and the potential transmission routes of hemoplasmas among bat population, bats and bat-ectoparasites including bat-flies, bat-mites, and bat-ticks were collected in Eastern and Central China from 2015 to 2021, and tested with PCR for hemoplasmas 16S rRNA gene. Based on 16S rRNA PCR, 18.0% (103/572) adult bats were positive for hemoplasmas, but none of 11 fetuses from hemoplasmas-positive pregnant bats was positive for hemoplasmas. These results indicated that adult bats had a high prevalence of hemoplasma, but vertical transmission of hemoplasmas did not occurr in the bats. Based on the 16S rRNA gene PCR, the minimum infection rate of bat-ectoparasite for hemoplasmas was 4.0% (27/676), suggesting that bat-ectoparasite also had a high prevalence for hemoplasmas. Phylogenetic analysis revealed that bat hemoplasmas from this study clustered into 4 genotypes (I-IV). Genotype I clustered together with hemoplasmas identified in bats from America. Genotype II shared high similarity with a human-pathogenic hemoplasma Candidatus Mycoplasma haemohominis. Genotype III and IV were unique, representing 2 new hemoplasma genotypes. Only genotype I was identified in both bats and all bat-ectoparasites including bat-flies, bat-mites, and bat-ticks. In conclusion, bats and bat-ectoparasites from China harbored abundant genetically diverse hemoplasmas including potential human-pathogenic hemoplasmas, indicating bats and bat-ectoparasites may play important roles in the maintenance and transmission of hemoplasmas in the natural foci.

Commentary: Case report: Daratumumab treatment in pre-transplant alloimmunization and severe hemolytic anemia.

Pereda et al. recently reported three cases in which daratumumab was utilized to reduce the 36 burden of red blood cell (RBC) and human leukocyte antigen (HLA) alloantibodies (1). These 37 cases support the need for further investigation into the potential use of daratumumab and related 38 plasma cell depletion therapies for patients with significant alloimmunization. However, the 39 authors' cases, particularly cases 1 and 2 in which the authors describe patients with sickle cell 40 disease (SCD) and multiple RBC antibodies, lack sufficient immunohematology and transfusion 41 details to reliably conclude the effectiveness and safety of daratumumab to reduce and existing alloantibodies can persist despite daratumumab treatment (3-6). Secondly, the 80 authors fail to acknowledge the possibility that the alloantibodies may have disappeared naturally 81 through the phenomenon of evanescence. Numerous studies have shown that many patients' 82 RBC alloantibodies will decline in titer to levels below a detectable threshold without further 83 exposure (7-9). Though the loss of all antibodies due to evanescence may be less likely, not 84 accounting for this potential mechanism of a waning antibody is concerning. 85 86 Furthermore, literature demonstrates that even if these antibodies have become undetectable, 87 these patients may still be at risk for DHTRs (10-13).

Early Myoclonic Infantile Encephalopathy in Neonate Caused by 5-Oxoprolinuria, a Rare Metabolic Entity: A Case Report

Neonatal encephalopathy is a common entity encountered by treating physicians in any neonatal intensive care unit. Though hypoxic ischaemic encephalopathy is the most frequent cause in developing countries, metabolic causes should also be looked for in refractory neonatal seizures with sibling death and parental consanguinity. Early myoclonic infantile encephalopathy, considered under the broad spectrum of infantile encephalopathy, is a rare syndrome in infants with onset within 3 months of age. It is characterized by myoclonic seizures, features of encephalopathy and caused by underlying metabolic diseases, nonketotic hyperglycinemia being the most common cause. On contrary its close mimicker, Ohtahara syndrome or early infantile epileptic encephalopathy is most likely associated with structural neurological lesions. We report a 12-day term Indian male neonate, born of second degree consanguinity with multiple sibling death history, presented with refractory myoclonic seizures in spite of uneventful birth history. Myoclonic seizures, refractory to intravenous phenobarbitone, phenytoin and infusion Midazolam, persisted after ruling out hypoglycemia, dyselectrolytemia, and neonatal sepsis. EEG showed typical burst suppression pattern pointing towards diagnosis of early myoclonic infantile encephalopathy. Further metabolic causes were looked for but tandem mass spectrometry for dried blood sample was normal. Lastly, urinary GCMS revealed 5-oxoprolinuria, an autosomal recessive condition, characterized by acidosis, jaundice, and severe hemolytic anemia among neonates, primarily due to glutathione synthetase enzyme deficiency. In severe form of 5-oxoprolinuria, neurological complications in form of seizures, ataxia have been documented in earlier studies; however, its association with myoclonic encephalopathy is yet to be reported in the literature and this report may be the first of its kind.

Enhanced phosphatidylserine exposure and erythropoiesis in Babesia microti-infected mice

IntroductionBabesia microti (B. microti) is the dominant species responsible for human babesiosis, which is associated with severe hemolytic anemia and splenomegaly because it infects mammalian erythrocytes. The actual prevalence of B. microti is thought to have been substantially underestimated.MethodsIn this study, Bagg’s albino/c (BALB/c) mice were intraperitoneally injected with B. microti-infected erythrocytes, and parasitemia was subsequently measured by calculating the proportion of infected erythrocytes. The ultrastructure of infected erythrocytes was observed using scanning and transmission electron microscopes. Quantifying phosphatidylserine (PS) exposure, oxidative stress, intracellular Ca2+, and erythropoiesis of erythrocytes were done using flow cytometry. The physiological indicators were analyzed using a Mindray BC-5000 Vet automatic hematology analyzer.ResultsOf note, 40.7 ± 5.9% of erythrocytes changed their structure and shrunk in the B. microti-infected group. The percentage of annexin V-positive erythrocytes and the levels of reactive oxygen species (ROS) in the erythrocytes were higher in the B. microti-infected group than in the control group at 10 dpi. Significant splenomegaly and severe anemia were also observed following B. microti infection. The parasitemia level in the B. microti-infected splenectomized group was higher than that of the B. microti-infected sham group. The population of early erythroblasts increased, and the late erythroblasts decreased in both the bone marrow and spleen tissues of the B. microti-infected group at 10 dpi.DiscussionPS exposure and elevated ROS activities were hallmarks of eryptosis in the B. microti-infected group. This study revealed for the first time that B. microti could also induce eryptosis. At the higher parasitemia phase, the occurrence of severe anemia and significant changes in the abundance of erythroblasts in B. microti-infected mice group were established. The spleen plays a critical protective role in controlling B. microti infection and preventing anemia. B. microti infection could cause a massive loss of late erythroblasts and induce erythropoiesis.

Enhanced phosphatidylserine exposure and erythropoiesis in Babesia microti-infected mice.

Babesia microti (B. microti) is the dominant species responsible for human babesiosis, which is associated with severe hemolytic anemia and splenomegaly because it infects mammalian erythrocytes. The actual prevalence of B. microti is thought to have been substantially underestimated. In this study, Bagg's albino/c (BALB/c) mice were intraperitoneally injected with B. microti-infected erythrocytes, and parasitemia was subsequently measured by calculating the proportion of infected erythrocytes. The ultrastructure of infected erythrocytes was observed using scanning and transmission electron microscopes. Quantifying phosphatidylserine (PS) exposure, oxidative stress, intracellular Ca2+, and erythropoiesis of erythrocytes were done using flow cytometry. The physiological indicators were analyzed using a Mindray BC-5000 Vet automatic hematology analyzer. Of note, 40.7 ± 5.9% of erythrocytes changed their structure and shrunk in the B. microti-infected group. The percentage of annexin V-positive erythrocytes and the levels of reactive oxygen species (ROS) in the erythrocytes were higher in the B. microti-infected group than in the control group at 10 dpi. Significant splenomegaly and severe anemia were also observed following B. microti infection. The parasitemia level in the B. microti-infected splenectomized group was higher than that of the B. microti-infected sham group. The population of early erythroblasts increased, and the late erythroblasts decreased in both the bone marrow and spleen tissues of the B. microti-infected group at 10 dpi. PS exposure and elevated ROS activities were hallmarks of eryptosis in the B. microti-infected group. This study revealed for the first time that B. microti could also induce eryptosis. At the higher parasitemia phase, the occurrence of severe anemia and significant changes in the abundance of erythroblasts in B. microti-infected mice group were established. The spleen plays a critical protective role in controlling B. microti infection and preventing anemia. B. microti infection could cause a massive loss of late erythroblasts and induce erythropoiesis.