Hereditary spherocytosis in association with severe G6PD deficiency: report of an unusual case

Prabhakar S Kedar; Roshan B Colah; Kanjaksha Ghosh; Dipika Mohanty

doi:10.1016/j.cccn.2004.02.021

Hematological and molecular analysis of patients with G6PD deficiency revealed coexistent hereditary spherocytosis and alpha thalassemia

Annals of Human Genetics ◽

10.1111/ahg.12451 ◽

2021 ◽

Author(s):

Lourdes del Carmen Rizo‐delaTorre ◽

Isis Mariela Herrera‐Tirado ◽

Rubiceli Hernández‐Peña ◽

Bertha Ibarra‐Cortés ◽

Francisco Javier Perea‐Díaz

Keyword(s):

Molecular Analysis ◽

G6pd Deficiency ◽

Hereditary Spherocytosis ◽

Alpha Thalassemia

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Glycosylated haemoglobin: a false sense of security

BMJ Case Reports ◽

10.1136/bcr-2018-227668 ◽

2018 ◽

Vol 11 (1) ◽

pp. e227668

Author(s):

Emily Finan ◽

Joe Joseph

Keyword(s):

Unusual Case ◽

Hereditary Spherocytosis ◽

Reticulocyte Count ◽

Blood Film ◽

Glycosylated Haemoglobin ◽

Sense Of Security ◽

Peripheral Blood Film ◽

False Sense ◽

History Of

We report the unusual case of a patient found to have a low glycosylated haemoglobin (HbA1c) despite having recently been diagnosed with diabetes mellitus type 2. The patient, who was not anaemic, with no symptoms or family history of haematological conditions, was subsequently found to have an elevated reticulocyte count, inferring increased red cell turnover as the culprit for the discordant HbA1c result. A diagnosis of hereditary spherocytosis was made based on characteristic peripheral blood film appearances and confirmed by eosin-5-maleimide binding test. Exposure of an undiagnosed haemolytic anaemia by virtue of a low HbA1c is uncommon. However, conditions that distort HbA1c measurements are not infrequent. This case should serve to remind clinicians of the limitations of HbA1c in specified situations, and to remain vigilant when interpreting results.

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Altered Erythrocyte Membrane Protein Phosphorylation in an Unusual Case of Hereditary Spherocytosis

Scandinavian Journal of Haematology ◽

10.1111/j.1600-0609.1979.tb02700.x ◽

2009 ◽

Vol 23 (3) ◽

pp. 251-255 ◽

Cited By ~ 4

Author(s):

Pierre Boivin ◽

Jean Delaunay ◽

Colette Galand

Keyword(s):

Membrane Protein ◽

Protein Phosphorylation ◽

Erythrocyte Membrane ◽

Unusual Case ◽

Hereditary Spherocytosis ◽

Erythrocyte Membrane Protein

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Hereditary Hemolytic Anemias Other Than Thalassemia: Single Center Experience

Blood ◽

10.1182/blood-2019-121702 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4855-4855

Author(s):

Gul Nihal Ozdemir ◽

Mehmet Akif Kilic

Keyword(s):

Family History ◽

Pyruvate Kinase ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

G6pd Deficiency ◽

Chelating Agents ◽

Hereditary Spherocytosis ◽

Conflicts Of Interest ◽

Single Center ◽

Pyruvate Kinase Deficiency

Aim: The aim of this study was to evaluate the demographic information, clinical and hematologic findings and treatment response of patients diagnosed with hereditary hemolytic anemias other than thalassemia at a single center. Materials and Methods: A total of 157 children with a diagnosis of hereditary hemolytic anemia except thalassemia were included. Patients' files were reviewed retrospectively. Demographic, clinical and laboratory characteristics, family history, complications, history of splenectomy and cholecystectomy, splenectomy response, use of chelating agents and other treatments, first transfusion age and transfusion frequency of patients were evaluated. Mean, standard deviation, median and 25-75 percentile values were used when descriptive analysis were presented. Mann Whitney U and Kruskal Wallis Tests were used for nonparametric groups. Pearson Chi Square and Fisher Tests were used when categorical comparisons were made. A value of P <0.05 was considered statistically significant. Results: Of the 157 patients , 101 patients (64,3%) had hereditary spherocytosis, 39 patients had (24,8%) glucose-6 phosphate dehydrogenase deficiency (G6PD), 15 patients had (9,6%) sickle cell anemia and 2 patients had (1.3%) pyruvate kinase deficiency. Sixty-one patients (38,9%) were girls and 96 were boys (61,1%). Median age of diagnosis was 10 months (range 1-188 months). Of 97 patients whom family history was questioned, 63 (64.9%) had family history. Most common complaint at diagnosis was paleness. Eighty-two patients had splenomegaly. Twenty-two patients (14%) had cholecystectomy and 56 patients (35.7%) had splenectomy on follow-up. The most frequent indication for splenectomy was hereditary spherocytosis. Fifty-eight (36.9%) patients required regular transfusion. Mean ferritin level of all was 506.3±1175.0. Patients with pyruvate kinase had the highest ferritin levels. Erythropoietin was used for 1 patient with hereditary spherocytosis in infancy without a response. Ten of 15 patients with sickle cell anemia were using hydroxyurea. Thirteen percent of all were using chelating agents. Conclusion: Hereditary spherocytosis and G6PD deficiency were the most common hereditary hemolytic anemias except thalassemia in our center. Family history was more frequent in hereditary spherocytosis compared to other hereditary hemolytic anemias. Patients with G6PD deficiency were diagnosed earlier than other hereditary hemolytic anemias. Hereditary spherocytosis was the most common indication for splenectomy and eliminated/decreased transfusion requirement in 96%. Patients with other hemolytic anemias had lower iron load compared to thalassemia except pyruvate kinase deficiency patients. Disclosures No relevant conflicts of interest to declare.

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Disease-modifying influences of coexistent G6PD-deficiency, Gilbert syndrome and deletional alpha thalassemia in hereditary spherocytosis: A report of three cases

Clinica Chimica Acta ◽

10.1016/j.cca.2016.04.020 ◽

2016 ◽

Vol 458 ◽

pp. 51-54 ◽

Cited By ~ 9

Author(s):

Manu Jamwal ◽

Anu Aggarwal ◽

Verinder Kumar ◽

Prashant Sharma ◽

Man Updesh Singh Sachdeva ◽

...

Keyword(s):

G6pd Deficiency ◽

Hereditary Spherocytosis ◽

Gilbert Syndrome ◽

Alpha Thalassemia ◽

Disease Modifying

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Genetic Spectrum of Inherited/Congenital Hemolytic Anemias in Indian Patients

Blood ◽

10.1182/blood-2021-154452 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4151-4151

Author(s):

Reena Das ◽

Manu Jamwal ◽

Prashant Sharma ◽

Deepak Bansal ◽

Amita Trehan ◽

...

Keyword(s):

Blood Cell ◽

Red Blood Cell ◽

G6pd Deficiency ◽

Laboratory Tests ◽

Hereditary Spherocytosis ◽

Cost Effective ◽

Accurate Diagnosis ◽

Evidence Based ◽

Common Causes ◽

Unstable Hemoglobins

Abstract Introduction Hemolytic anemias are a group of disorders caused by the premature destruction of red blood cells with reticulocytosis. Common causes of inherited/congenital hemolysis are hemoglobinopathies and thalassemia syndromes, red blood cell membrane, and enzyme disorders. Most of the common causes (thalassemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, etc.) are diagnosed based on laboratory testing; however, for remaining causes laboratory tests are either inaccessible or cumbersome. We follow a stepwise diagnostic pipeline and red cell morphology is helpful with membrane disorders. Phenotypes vary from severe hemolysis (transfusion-dependent) to mild/asymptomatic patients. Undiagnosed haemolytic anemias are taken up for multi-gene panel-based targeted resequencing which is rapid, accurate, and cost-effective. The use of these panels expedites the diagnoses of inherited hemolytic anemias and is eventually helpful for evidence-based genetic counseling. Objectives This study aimed to determine the genetic defects in inherited/congenital hemolytic anemias which remained unexplained after routine laboratory tests. Methods Seventy-five families were enrolled based on the clinical and laboratory features of inherited/congenital hemolytic anemias. Common causes of inherited hemolysis are G6PD deficiency, hemoglobinopathies and thalassemia syndromes, autoimmune hemolytic anemias, hereditary spherocytosis, and pyruvate kinase (PK) deficiency were excluded on the basis of biochemical and molecular tests. DNA extraction was done QIAamp DNA Blood Mini Kit. Quantity and quality of DNA were verified using NanoDrop and Qubit Fluorometer respectively. DNA libraries were prepared using Amplicon custom panels for genes implicated in hemolytic anemias and sequenced on Illumina MiSeq Sequencer. Alignment and variant calling were done in Illumina Local run Manager and Variant annotation was done in Basespace VariantInterpretor. Sanger sequencing was done as orthogonal validation in the index case. Predictive testing was performed for the family members. Results After targeted resequencing of the total 75 index cases, 19 patients were found to have red blood cell enzymopathies, 15 patients had stomatocytosis, 13 had membranopathies and three patients had unstable hemoglobins. In 8 patients cause was not established either only heterozygous variant was found for autosomal recessive or due to the lack of samples of family members for screening. Seventeen cases remained unexplained even after next-generation sequencing. Out of 19 patients, unexpected PK deficiency was found in 12 patients and G6PD deficiency was found in 3 patients; despite the enzyme assay being normal in these cases. We also found 2 patients with glucose-6-phosphate isomerase deficiency. One case each with hexokinase deficiency and glutathione synthetase deficiency was found. Among 15 patients with stomatocytosis, 8 had Mediterranean stomatocytosis/macrothrombocytopenia (ABCG5/ABCG8). These 8 patients showed the presence of stomatocytosis along with giant platelets on peripheral smear evaluation. Of the remaining 7 cases , 2 were found to have overhydrated hereditary stomatocytosis (RHAG) and dehydrated Stomatocytosis/xerocytosis was found in 5 (PIEZO1/KCNN4). We also found 13 cases of hemolytic anemia to have a genetic defect in red blood cell membrane protein-coding genes. Of these 5 had probably pathogenic variants in the ANK1 gene, 5 had a pathogenic variant in SPTA1, 2 had SPTB 2, and 1 patient SLC4A1. We also encountered 3 cases of unstable hemoglobins where no abnormality was noted in Hb-HPLC patterns. A total of seven patients underwent splenectomy and are transfusion free. Conclusions Our cohort of 75 families of hemolytic anemia of unexplained etiology showed a highly heterogeneous genetic spectrum. Of the total cases, the confirmed diagnosis was achieved in 67% of the patients. This approach of using a multi-gene panel is cost-effective and can provide a rapid and accurate diagnosis. Unexpected PK deficiency, G6PD deficiency, and unstable hemoglobins suggest that such cases can be missed. Providing accurate diagnosis in such cases provides evidence-based counseling and saves the families from inappropriate treatments. Disclosures No relevant conflicts of interest to declare.

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