Academic literature on the topic 'Inherited anaemias'
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Journal articles on the topic "Inherited anaemias"
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Roberts-Harewood, Marilyn. "Inherited haemolytic anaemias." Medicine 37, no. 3 (March 2009): 143–48. http://dx.doi.org/10.1016/j.mpmed.2009.01.002.
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Weatherall, DJ, and AB Provan. "Red cells I: inherited anaemias." Lancet 355, no. 9210 (April 2000): 1169–75. http://dx.doi.org/10.1016/s0140-6736(00)02073-0.
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Kesse-Adu, Rachel, and Jo Howard. "Inherited anaemias: sickle cell and thalassaemia." Medicine 41, no. 4 (April 2013): 219–24. http://dx.doi.org/10.1016/j.mpmed.2013.01.012.
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Kesse-Adu, Rachel, and Jo Howard. "Inherited anaemias: sickle cell and thalassaemia." Medicine 45, no. 4 (April 2017): 214–20. http://dx.doi.org/10.1016/j.mpmed.2017.01.005.
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Kesse-Adu, Rachel, and Jo Howard. "Inherited anaemias: sickle cell and thalassaemia." Medicine 49, no. 4 (April 2021): 210–16. http://dx.doi.org/10.1016/j.mpmed.2021.01.006.
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Dokal, Inderjeet, and Tom Vulliamy. "Inherited aplastic anaemias/bone marrow failure syndromes." Blood Reviews 22, no. 3 (May 2008): 141–53. http://dx.doi.org/10.1016/j.blre.2007.11.003.
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Mayhew, Rachel, Frances Smith, Laura Steedman, Nicholas Parkin, Eva Moldes Beiro, Peter Rushton, Alison Bybee, et al. "A Review of 1000 Molecular Investigations of Rare Inherited Anaemia and Related Conditions with the Red Cell Gene Panel." Blood 132, Supplement 1 (November 29, 2018): 3609. http://dx.doi.org/10.1182/blood-2018-99-118799.
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Abstract The genetic diagnosis of inherited anaemias is an important aspect of the diagnostic pathway for patients with haematological disorders, allowing discrimination between conditions of overlapping phenotypes therefore enabling more effective clinical treatment. Next Generation sequencing platforms are now in widespread use in diagnostic settings and are facilitating more rapid, accurate and cost-effective molecular diagnosis. The Red Cell Gene Panel developed by the Viapath Molecular Pathology laboratory based at King's College Hospital, London has harnessed this technology with the aim of identifying genetic diagnoses of rare inherited causes of anaemia. Although originally setup to diagnose inherited red cell disorders, clinical demand has led to the inclusion of inherited bone marrow failure syndromes and other related conditions such that the panel now consists of 194 genes, divided into 16 subpanels (see table 1). Here we present the data from the first 1000 diagnostic cases reported under the following referral groups: 462 cases of unexplained anaemia (including haemolytic anaemia, sideroblastic anaemia, congenital dyserythropoietic anaemia, Diamond-Blackfan Anaemia), 232 cases of inherited bone marrow failure syndromes (including thrombocytopenia and neutropenia), 163 cases of congenital erythrocytosis and 143 other cases (including but not limited to iron regulation, haemophagocytic lymphohistiocytosis (HLH) and Criggler-Najjar ). Of these 1000 cases, we have achieved an overall diagnostic yield of approximately 25%. A diagnosed case is defined here as one in which a clear pathogenic or likely pathogenic variant that explains the phenotype has been detected. The unexplained anaemia cases have achieved the highest percentage of cases diagnosed with 47% diagnostic yield and data will be presented outlining the gene-by-gene breakdown of diagnoses made. Our bespoke bioinformatics pipeline has also allowed the detection of novel disease-causing structural variants in 20 cases, contributing 2% of our diagnostic yield. These are detected using three different methods; read-depth analysis, split-read mapping and discordant insert-size analysis. All reported structural variants have been confirmed with a second method, either breakpoint mapping or dosage-sensitive PCR. A significant proportion of cases (28%) have been reported with variants of uncertain clinical significance, highlighting the need for family studies and functional characterisation to be able to accurately ascertain the significance of these variants. Future developments of the service include functional characterisation of membrane disorders using next generation ektacytometry and preliminary data from this work will be presented here. Disclosures Kulasekararaj: Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Other: Travel Support . Pagliuca:Gentium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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Rawa, Katarzyna, Anna Adamowicz-Salach, Michał Matysiak, Anna Trzemecka, and Beata Burzynska. "Coexistence of Gilbert syndrome with hereditary haemolytic anaemias." Journal of Clinical Pathology 65, no. 7 (May 3, 2012): 663–65. http://dx.doi.org/10.1136/jclinpath-2011-200580.
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BackgroundGilbert syndrome is an inherited disease characterised by mild unconjugated hyperbilirubinaemia caused by mutations in UGT1A1 gene which lead to decreased activity of UDP-glucuronosyltransferase 1A1. The most frequent genetic defect is a homozygous TA dinucleotide insertion in the regulatory TATA box in the UGT1A1 gene promoter.Methods and results182 Polish healthy individuals and 256 patients with different types of hereditary haemolytic anaemias were examined for the A(TA)nTAA motif. PCR was performed using sense primer labelled by 6-Fam and capillary electrophoresis was carried out in an ABI 3730 DNA analyser. The frequency of the (TA)7/(TA)7 genotype in the control group was estimated at 18.13%, (TA)6/(TA)7 at 45.05% and (TA)6/(TA)6 at 36.26%. There was a statistically significant difference in the (TA)6/(TA)6 genotype distribution between healthy individuals and patients with glucose-6-phosphate dehydrogenase deficiency (p=0.041). Additionally, uncommon genotypes, (TA)5/(TA)6, (TA)5/(TA)7 and (TA)7/(TA)8 of the promoter polymorphism, were discovered.ConclusionGenotyping of the UGT1A1 gene showed distinct distribution of the common A(TA)nTAA polymorphism relative to other European populations. Because of a greater risk of hyperbilirubinaemia due to hereditary haemolytic anaemia, the diagnosis of Gilbert syndrome in this group of patients is very important.
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Korubo, Kaladada I., and Boma A. West. "Congenital Dyserythropoietic Anaemia: Case Report of a Rare Blood Disorder in a Nigerian Child." Blood 124, no. 21 (December 6, 2014): 4879. http://dx.doi.org/10.1182/blood.v124.21.4879.4879.
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Abstract Introduction The congenital dyserythropoietic anaemias (CDA) are a rare group of inherited haemolytic anaemias characterized by ineffective erythropoiesis and dyserythropoiesis. Due to the rarity of this disorder (and in Africa where haemoglobinopathies are the commonest cause of congenital haemolytic anaemias), the diagnosis can be missed. We report a six year old girl with recurrent anaemia, jaundice, hepatosplenomegaly and history of multiple transfusions who was diagnosed with CDA. Case Report A six year old girl presented to the paediatric clinic with a two year history of passing coke-coloured urine, recurrent anaemia requiring regular three-monthly transfusions and persistent jaundice. She was not a known sickle cell anaemia or thalassaemia patient. History of prenatal period, birth and delivery were normal (birth weight 3.5kg/ 7.7lbs). There was no history of neonatal jaundice or family history of similar illness. At presentation, she was acutely ill-looking, conscious but weak. She was afebrile, severely pale, icteric, tachypneic and in respiratory distress (respiratory rate of 52 cycles/minute). She was small for age; weight 15kg / 33.1lbs (below the 3rd percentile), height 104cm (below the 3rd percentile) with frontal bossing and gnathopathy. The liver was 6cm below the right costal margin and tender, with splenomegaly- 5cm below the costal margin. There was no lymphadenopathy. Her chest was clear, heart rate 140 beats/minute, and blood pressure of 100/50mmHg with presence of a haemic murmur. A preliminary clinical diagnosis of recurrent severe haemolytic anaemia in heart failure secondary to haemoglobinopathy was made. Full blood count showed severe anaemia with haemoglobin (Hb) concentration of 5.1g/dL, normal red cell indices, white cell count- 13.6 X 109/L, platelets- 191 X 109/L and reticulocyte count- 1.3%. The Hb genotype was AA, direct and indirect antiglobulin test were negative. Liver functions tests showed normal enzyme and protein values; but high total bilirubin (104mmol/L) and unconjugated bilirubin- 17.4umol/L. Serum uric acid was normal. HIV, hepatitis B and C were negative. Urinalysis was positive for blood, urobilinogen, bilirubin, with a pH of 8.0. Urine microscopy showed granular, epithelial and red blood cell casts. Glucose-6-phosphate dehydrogenase assay- 12.5 μ/Hb. She was admitted, placed on oxygen, transfused and discharged on the third day in stable condition. However she was brought back to the hospital about 3 months later for similar symptoms. Urgent Hb concentration was 6.0g/dL. Peripheral blood film revealed anisopoikilocytosis, some macrocytes, tear drop cells, polychromasia, basophilic stippling, fragmented red cells and presence of nucleated red cells (12/100 white cells)- a few of which were multinucleated (Fig 1). HPLC showed low HbA (74.1%), severely increased HbF (23.8%) and HbA2 (2.1%). Bone marrow (BM) aspiration showed a hypercellular marrow, erythroid hyperplasia (myeloid/erythroid ratio 1:2), dyserythropoiesis with erythroid multinuclearity in >10% of late erythroid precursors and significant karyorrhexis. Myelopoiesis and megakaryopoiesis were essentially normal (Fig 2). Serum ferritin was elevated (2,658ng/ml). In the absence of availability of electron microscopy or molecular studies, a diagnosis of CDA type II was made based on clinical, laboratory and characteristic bone marrow findings. She was transfused, placed on iron chelation therapy, her parents counseled on treatment options and she is being followed up. Discussion The CDAs are classically grouped into 3 types based on bone marrow morphology. Type I has erythroblasts joined by an internuclear bridge. Type II erythroblasts have multinuclearity of late erythroblasts while type III has gigantoblasts (erythroblasts with ≥8 nuclei). Inheritance is autosomal recessive and diagnosis is usually in childhood or early adult life. Common clinical findings are anaemia, jaundice and splenomegaly; however these are seen in other more common inherited haemolytic anaemias. BM examination is the gold standard for diagnosis. Patients with CDA usually have high serum ferritin that may require iron chelation therapy. CDA although rare must be considered in a child who has recurrent anaemia in whom other causes have been excluded. BM examination remains a key diagnostic tool in identification of the CDAs. Fig 1: Blood Film Fig 1:. Blood Film Fig 2: Bone Marrow Fig 2:. Bone Marrow Disclosures No relevant conflicts of interest to declare.
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Roy, Noémi B. A., Paul Telfer, Perla Eleftheriou, Josu de la Fuente, Emma Drasar, Farrukh Shah, David Roberts, et al. "Protecting vulnerable patients with inherited anaemias from unnecessary death during the COVID‐19 pandemic." British Journal of Haematology 189, no. 4 (May 2020): 635–39. http://dx.doi.org/10.1111/bjh.16687.
Full textDissertations / Theses on the topic "Inherited anaemias"
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Brown, Jennifer Mary. "The molecular basis of beta-thalassaemia in Burma." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.276507.
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Dokal, Inderjeet Singh. "Studies on the basis of the inherited bone marrow failure syndromes : Fanconi's anaemia and dyskeratosis congenita." Thesis, University of Leicester, 1994. http://hdl.handle.net/2381/34327.
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A number of inherited disorders are associated with bone marrow failure. Amongst them Fanconi's anaemia (FA) is the most common and, together with dyskeratosis congenita (DC), the best characterized. The aim of this study was twofold: A. To devise a strategy which may prermit "expression cloning" of the FA genes. B: To characterise cytogenetic (and molecular) features of cells from FA and DC patients which may provide a better understanding of the basis of these disorders. As a first step towards cloning the gene (s) for Fanconi's anaemia (FA) I devised a selection system [based on the DNA cross-linking agents mitomycin-c (MMC) and diepoxybutane (DEB)] that discriminates between FA and normal cells. 'Mixing experiments' (where approximately 10 normal cells were co-plated with 106 FA cells) demonstrated that it is possible to kill FA cells at high density without significantly affecting the cloning efficiency of normal cells. Transfection of FA fibroblasts with normal DNA (mouse genomic, human genomic, and human cDNA) either by calcium phosphate precipitation or by electroporation yielded 11 DEB and MMC resistant colonies. However, southern analysis of the DNA from these colonies with the appropriate probes gave no positive signal, and thus no "handle" to recover the FA gene (s). Experiments addressing the effect of the specific DNA topoisomerase I inhibitor, camptothecin, on FA and normal cells showed: 1. The FA lymphocytes have increased chromosomal breakage compared to normal lymphocytes after incubation with camptothecin (p=0.006). 2. Incubation of peripheral blood lymphocytes (pbl) from normal subjects with camptothecin, produced the same type of chromosomal breakage as that seen in FA lymphocytes. 3. FA fibroblasts were more sensitive to camptothecin than normal fibroblasts. These data are compatible with either a defect which makes topoisomerase I more crucial, or its function being abnormal in some FA patients. In patients with DC, primary skin fibroblast cultures were abnormal in both morphology and growth rate. Survival studies using 4 clastogens and gamma-irradiation showed no significant difference between DC and normal fibroblasts. Cytogenetic studies performed on pbl showed no difference between DC and normal lymphocytes with or without prior incubation with clastogens. However, bone marrow from 1 out of 3 patients and fibroblasts from 2 out of 4 patients showed numerous unbalanced chromosomal rearrangements in the absence of clastogenic agents. Although patients with FA and DC share some features in common they appear to differ in two fundamental ways: Firstly, unlike Fanconi cells, DC cells are not hypersensitive to clastogens. Secondly the primary defect in DC appears to predipose cells to developing chromosomal rearrangements rather than to chromosomal gaps and breaks seen in FA.
Books on the topic "Inherited anaemias"
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Bunch, Chris. Haemolytic anaemia. Edited by Patrick Davey and David Sprigings. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199568741.003.0280.
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Haemolytic anaemias occur when the rate of red-cell breakdown is increased and exceeds the marrow’s capacity to generate new cells. Increased red-cell destruction, or haemolysis, may reflect a broad range of disorders. Some involve intrinsic defects in the red cell itself; in others, the red cells are normal but are subjected to external factors which lead to premature destruction. Many of the intrinsic defects are due to inherited disorders affecting the red-cell membrane, its enzymes, or haemoglobin. The marrow can normally compensate for moderate haemolysis by increasing red-cell production up to tenfold. Only when haemolysis is severe and the red-cell lifespan is reduced to less than about 15 days, or the marrow is unable to compensate, will anaemia occur. This chapter addresses the diagnosis, investigation, and management of haemolytic anaemias, including hereditary spherocytosis, paroxysmal nocturnal haemoglobinuria, glucose-6-phosphate dehydrogenase deficiency, haemoglobinopathies, and mechanical and immune haemolytic anaemias.
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Ladani, Sapna, Beverley J. Hunt, and Sue Pavord. Obstetric haematology. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780198713333.003.0048.
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This chapter aims to cover aspects of haematology of pregnancy, delivery, and postpartum that are not addressed in other chapters. Obstetric haematology is a vast and complex area, the importance of which has promoted the development of this as a unique subspecialty. Thrombosis and bleeding, anaemia, haemoglobinopathies, and microangiopathies still account for significant morbidity and mortality in pregnancy, despite improvements in recognition, prevention, and management. Anaemia, due to iron deficiency, is highly prevalent in the pregnant population, but with early recognition and treatment, morbidity and need for unnecessary blood transfusion can be avoided. The management of women with thrombocytopenias and inherited bleeding disorders can be complex because of the haemostatic challenges of pregnancy. Pregnancies in women with haematological disorders need to be carefully managed to reduce mortality and morbidity in the mother and fetus. This chapter addresses the management of anaemia, haemoglobinopathies (mainly sickle cell disease), thrombocytopenia, microangiopathies, and the inherited bleeding disorders.
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Sayer, John A. Autosomal dominant tubule-interstitial kidney disease, including medullary cystic disease. Edited by Neil Turner. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0318_update_001.
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The term medullary cystic kidney disease (MCKD) describes a group of autosomal dominantly inherited renal disorders. The term MCKD is used interchangeably with other terms, most commonly autosomal dominant interstitial kidney disease, and now may be distinguished using a molecular genetic diagnosis into at least three types. These include MCKD type 1, MCKD type 2 (also known now as uromodulin-associated kidney disease), and REN-associated kidney disease. Each of these types have phenotypic overlap but with a few distinguishing features. MCKD typically leads to end-stage renal failure between 30 and 70 years of age. Extrarenal features may include gout and childhood anaemia.
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Shrivastava, Seema, Beverley J. Hunt, and Anthony Dorling. Coagulopathies in chronic kidney disease. Edited by David J. Goldsmith. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199592548.003.0135.
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Coagulation abnormalities are common in chronic kidney disease (CKD). Both haemorrhage and thrombosis are more common than in the general population. Haemorrhage, when it occurs, is associated with increased morbidity and mortality compared to that seen in non-uraemic patients. It is more likely spontaneously, but particularly in association with anti-platelet agents or anticoagulants. The increased risk of both arterial and venous thrombosis occurs in part because of the increase prevalence of traditional risk factors for thrombosis in CKD, in part because of the specific problems associated with nephrotic syndrome, and also because of specific putative prothrombotic factors associated with CKD, such as increased levels of coagulation factors and altered platelet function associated with uraemia. Two syndromes, both characterized by intravascular thrombosis can contribute to the development of CKD. The first is antiphospholipid syndrome, due to the presence of antibodies against negatively charged phospholipids, in which thrombosis of the renal vasculature is relatively common. The second is a group of conditions, the thrombotic microangiopathies, in which inherited or acquired deficiencies of ADAMTS13, antiphospholipid antibodies, or pathological endothelial cell activation in renal vessels, sometimes due to functional deficiencies of one or more proteins regulating coagulation or complement activation, leads to acute renal dysfunction associated with anaemia.
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Rees, David. Haemoglobinopathies. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0172.
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Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.
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Rees, David. Haemoglobinopathies. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199642489.003.0172_update_001.
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Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.
Book chapters on the topic "Inherited anaemias"
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Gilbert, Patricia. "Sickle cell anaemia." In The A-Z Reference Book of Syndromes and Inherited Disorders, 266–70. Boston, MA: Springer US, 1996. http://dx.doi.org/10.1007/978-1-4899-6918-7_70.
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Brown, Marvelle. "Inherited Haemolytic Anaemia: Pathophysiology, Care and Management." In Haematology Nursing, 107–16. West Sussex, UK: John Wiley & Sons, Ltd., 2013. http://dx.doi.org/10.1002/9781118702949.ch8.
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Dokal, Inderjeet S. "Inherited Aplastic Anaemia/Bone Marrow Failure Syndromes." In Postgraduate Haematology, 186–205. Oxford, UK: Wiley-Blackwell, 2010. http://dx.doi.org/10.1002/9781444323160.ch12.
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Dokal, Inderjeet S. "Inherited Aplastic Anaemia/Bone Marrow Failure Syndromes." In Postgraduate Haematology, 156–73. Oxford, UK: John Wiley & Sons, Ltd, 2015. http://dx.doi.org/10.1002/9781118853771.ch10.
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de Klerk, J. B. C., M. Duran, L. Dorland, H. A. A. Brouwers, L. Bruinvis, and D. Ketting. "A Patient with Mevalonic Aciduria Presenting with Hepatosplenomegaly, Congenital Anaemia, Thrombocytopenia and Leukocytosis." In Studies in Inherited Metabolic Disease, 233–36. Dordrecht: Springer Netherlands, 1988. http://dx.doi.org/10.1007/978-94-009-1259-5_40.
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Cox, Timothy M., and John B. Porter. "Iron metabolism and its disorders." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5371–402. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0534.
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Iron deficiency and iron storage disease—the latter principally due to inherited and acquired anaemias such as thalassemia—are disorders of massive clinical significance across the globe. Iron deficiency is the commonest cause of anaemia, affecting about 1 billion people, and about 0.75 million people have thalassaemia. Largely neglected by health services in rich and resource-poor countries alike, disorders of iron metabolism, whether inherited, nutritional, or otherwise, represent a long-standing public health challenge. Improved screening methods for detection, diagnosis, and appropriate supplementation—as well as genetic counselling—can offer a great deal to relieve the burden in stricken communities. Advances in chelation therapy have improved the survival of patients with iron-loading anaemias and transfusion-related haemochromatosis, and better understanding of the molecular pathophysiology of iron homeostasis now offers the prospect of definitive therapies to control pathological erythropoiesis and the inappropriate drive to acquire lethal quantities of toxic iron.
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Fuller, Stephen J., and James S. Wiley. "Anaemias resulting from defective maturation of red cells." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5450–56. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0538.
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Defective maturation of red cells leads to premature destruction of nucleated red cell precursors before they leave the haematopoietic bone marrow, which results in expansion of the marrow, haemolytic jaundice, peripheral signs of increased erythroid turnover on blood films, and (in long-standing disorders) iron overload due to enhanced absorption. Causes of ineffective erythropoiesis include (1) inhibition of erythroid DNA synthesis (e.g. megaloblastic anaemias (vitamin B12 or folate deficiency), drugs blocking DNA synthesis); (2) clonal disorders of erythropoiesis (e.g. refractory anaemia, acquired idiopathic sideroblastic anaemia, acute erythroleukaemia); (3) genetic disorders of erythropoiesis (e.g. thalassaemia syndromes, hereditary sideroblastic anaemia, congenital dyserythropoietic anaemia); and (4) other causes (e.g. alcohol). Sideroblastic anaemias—these result from defects in haem biosynthesis, with most cases being acquired as a clonal disorder of erythropoiesis, with varying degrees of myelodysplasia. Other causes are (1) hereditary (e.g. inherited deficiency of the erythroid-specific 5-aminolaevulinic acid synthase 2 gene on the X-chromosome causes congenital sideroblastic anaemia); (2) acquired (e.g. due to drugs or toxins such as ethanol, isoniazid, or lead; following chemotherapy or irradiation; or of unknown cause (idiopathic)). Diagnosis, treatment, and prognosis—diagnosis is achieved by finding ring sideroblasts (erythroblasts containing five or more iron-positive granules arranged in a perinuclear location around one-third or more of the nucleus) on bone marrow aspirate stained with Prussian blue iron reagent. Aside from supportive care with blood transfusion and iron chelation, a trial of pyridoxine is generally indicated (25% of hereditary cases—but few acquired cases—show some response). Acquired idiopathic sideroblastic anaemia has a median survival of 42 to 76 months, with 3 to 12% progressing to acute leukaemia.
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Roberts, Irene, and Inderjeet S. Dokal. "Inherited bone marrow failure syndromes." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5325–36. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0528.
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Inherited forms of bone marrow failure may involve all haematopoietic lineages or a single lineage. They are rare, but collectively account for 20 to 30% of patients presenting with aplastic anaemia. They may present at birth or in infancy or childhood, but also sometimes in adults. Associated somatic abnormalities may be helpful in diagnosis. Two of the best characterized syndromes are Fanconi’s anaemia and dyskeratosis congenita, both frequently associated with generalized bone marrow failure. Other well-recognized disorders lead to much more specific abnormalities affecting a single cell type (e.g. impaired red cell production in Diamond–Blackfan anaemia and impaired neutrophil production in Shwachman–Diamond syndrome) and reduced platelet production in thrombocytopenia with absent radii syndrome. Advances in understanding the genetics of inherited bone marrow failure syndromes have provided valuable insight into their pathophysiology, and also into normal haematopoiesis.
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Zanella, Alberto, and Paola Bianchi. "Erythrocyte enzymopathies." In Oxford Textbook of Medicine, edited by Chris Hatton and Deborah Hay, 5463–72. Oxford University Press, 2020. http://dx.doi.org/10.1093/med/9780198746690.003.0540.
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Numerous enzymes, including those of the hexose monophosphate and glycolytic pathways, are active in the red cell. They are required for the generation of ATP and the reductants NADH and NADPH. 2,3-Diphosphoglycerate, an intermediate of glucose metabolism, is a key regulator of the affinity of haemoglobin for oxygen, and accessory enzymes are also active for the synthesis of glutathione, disposal of oxygen free radicals, and for nucleotide metabolism. With the exception of heavy metal poisoning and rare cases of myelodysplasia, most red cell enzyme deficiency disorders are inherited. They may cause haematological abnormalities, (most commonly nonspherocytic haemolytic anaemias, but also rarely polycythaemia or methaemoglobinaemia, manifest with autosomal recessive or sex-linked inheritance), and may also be associated with nonhaematological disease when the defective enzyme is expressed throughout the body. Some may mirror important metabolic disorders, without producing haematological problems, making them of diagnostic value. Others are of no known clinical consequence. With rare exceptions, it is impossible to differentiate the enzymatic defects from one another by clinical or routine laboratory methods. Diagnosis depends on the combination of (1) accurate ascertainment of the family history; (2) morphological observations—these can determine whether haemolysis is present, rule out some causes of haemolysis (e.g. hereditary spherocytosis and other red blood cell membrane disorders), and diagnose pyrimidine 5′-nucleotidase deficiency (prominent red cell stippling); (3) estimation of red cell enzyme activity; and (4) molecular analysis. The most common red cell enzyme defects are glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, glucose-6-phosphate isomerase deficiency, pyrimidine 5′-nucleotidase deficiency—which may also induced by exposure to environmental lead—and triosephosphate isomerase deficiency.
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Waldmann, Carl, Andrew Rhodes, Neil Soni, and Jonathan Handy. "Haematological disorders." In Oxford Desk Reference: Critical Care, 431–49. Oxford University Press, 2019. http://dx.doi.org/10.1093/med/9780198723561.003.0024.
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This chapter discusses haematological disorders and includes discussion on bleeding disorders (including acquired bleeding disorders and inherited bleeding disorders), anaemia in critical care (including discussion on pathogenesis, consequences of anaemia, approach to the investigation of anaemia, classification of anaemia, measures to minimize blood loss in the intensive care unit [ICU], and erythropoietin). It also covers sickle cell anaemia (transfusion in sickle cell anaemia, including hyperhaemolysis, acute chest syndrome, and pulmonary hypertension in sickle cell disease), haemolysis (haemolytic conditions particularly relevant to critical care), disseminated intravascular coagulation, neutropenic sepsis (including persistent fever or inadequate clinical response, fungal infections, empirical antifungal therapy, viral infections, granulocyte-colony stimulating factor, and granulocytes for neutropenia). Finally, the chapter discusses haematological malignancies in the ICU (neutropenia and neutropenic sepsis, tumour lysis syndrome, hyperviscosity syndromes, hyperleukocytosis, haemorrhagic complications, haematopoietic stem cell transplant, graft versus host disease, and corticosteroids) and coagulation monitoring.
Conference papers on the topic "Inherited anaemias"
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O’Neill, Roisin, Olivia O’Mahony, and Niamh McSweeney. "GP235 COL4A1 mutation inherited from maternal mosaicism in an infant presenting with microcephaly, haemolytic anaemia and cataracts." In Faculty of Paediatrics of the Royal College of Physicians of Ireland, 9th Europaediatrics Congress, 13–15 June, Dublin, Ireland 2019. BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health, 2019. http://dx.doi.org/10.1136/archdischild-2019-epa.294.
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