Haematology
Kaji Sritharan, Jonathan Rohrer, Alexandra C Rankin, Sachi Sivananthan in Essential Notes for Medical and Surgical Finals, 2021
ALL is more common in children; AML and chronic leukaemias are more common in adults. Diagnosis is based on detecting serum paraprotein, serum free light chains, or urinary BJP and increased plasma cells in bone marrow, in association with evidence of end-organ damage, i.e. anaemia, hypercalcaemia, renal failure, peripheral neuropathy, lytic lesions on plain x-ray or MRI, amyloid. Diagnosis is made when tissue biopsy demonstrates apple green birefringence under polarised light following staining with Congo red, and using Serum Amyloid P (SAP) scanning in specialist centres. Treatment of AL amyloid is similar to that for symptomatic myeloma; treatment of AA amyloid requires management of the chronic inflammatory state. Reduced production of either alpha or beta globin chains leads to alpha and beta thalassaemia respectively. Usually taken from the posterior superior iliac spine, occasionally from the sternum (or tibia in children only); provides important information regarding haematopoiesis and infiltration of bone marrow with abnormal cells.
Prenatal diagnosis and reproductive genetics
Peter S. Harper in The Evolution of Medical Genetics, 2019
The possibility of diagnosing serious genetic disorders prenatally by amniocentesis coincided closely with the legalisation of termination of pregnancy in Britain and other countries during the 1960s and 1970s. Initially applied to Down syndrome and other chromosome disorders, then to neural tube defects, prenatal diagnosis gave parents the option of avoiding genetic risk and achieving a healthy family, but at psychological cost. Ethical issues were increased as more general prenatal screening was introduced, often without adequate information for the women involved or full consideration of their wishes. Medical geneticists have taken a cautious and at times critical approach to these developments but have been closely involved with studies of safety, early approaches such as chorion villus sampling, and noninvasive prenatal testing by analysis of fetal DNA in maternal blood. They have also worked for the provision of molecular prenatal diagnosis of disorders, such as the thalassaemias, in specific ethnic groups. New developments, such as preimplantation genetic diagnosis and gene editing technology, continue to give both ethical and practical challenges in reproductive genetics.
Biochemical Variation and Differential Disease Susceptibility
Theresa Overfield in Biologic Variation in Health and Illness, 2017
This chapter examines biochemical or enzymatic variations that occur among different races and that are of some health concern, such as lactose intolerance, differential drug metabolism, and malaria-related blood and enzyme types. A few of the racial differences in drug response may be the result of natural selection, wherein a food substance has effects similar to those of a drug. Isoniazid, a drug used to treat tuberculosis, is inactivated rapidly or slowly depending on an individual's phenotype. Malaria has brought about the evolutionary development of several hemoglobin and enzyme variants. Thalassemia is another malaria-related genetic condition that results in various degrees of anemia. Several types of cancer appear to vary by race, but a closer look often indicates that diet or another environmental factor is a better predictor than race. Diseases of the cardiovascular system are the leading cause of death in the United States, Coronary artery disease, hypertensive heart disease, and stroke all vary in frequency by race.
Thalassemia Intermedia Caused by 16p13.3 Sectional Duplication in a β-Thalassemia Heterozygous Child
Published in Pediatric Hematology and Oncology, 2015
Sha Liu, Hua Jiang, Man-Yu Wu, Yong-Ling Zhang, Dong-Zhi Li
Thalassemia intermedia is an inherited hemoglobin disorder characterized by a significant genetic and clinical heterogeneity. A wide spectrum of different genotypes—homozygous, heterozygous, and compound heterozygous—have been found to be responsible for it. The authors describe a Chinese child of β-thalassemia heterozygote with the mutation IVS2-654 (C→T) (HBB:c.316-197C→T) presenting with severe thalassemia intermedia. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α gene cluster revealed an approximate 146-kb duplication at 16p13.3 including the complete α gene cluster. The duplicated allele and the normal allele in trans result in a total of 6 active α genes. The severe clinical phenotype seemed to be related to the considerable excess of the α-globin and the β-globin deficit caused by the presence of the β-thalassemia. The α gene duplication should be considered in patients heterozygous for β-thalassemia who show a more severe phenotype than β-thalassemia trait.
Thalassemia Incidence and Treatment in China with Special Reference to Shenzhen City and Guangdong Province
Published in Hemoglobin, 2009
Chang-Gang Li, Chun-Fu Li, Qi Li, Ming Li
According to the data from different screening studies, thalassemia is the most commonly seen hereditary hemolytic disease in China. The reported prevalence of thalassemia carriers varies but it is most prevalent in Southern China. In the past, the outcome of patients with thalassemia major has been very poor due to unfavorable economic background. With economic improvement in the past 10 years, increasing number of patients can get regular transfusion and chelation, and more patients can be treated by hemopoietic stem cell transplantation. A better prevention network has been built up over the years, but there are still babies being born with severe forms of thalassemia every year. A more comprehensive preventive program and public education are vital.
Joint Diabetes Thalassaemia Clinic: An Effective New Model of Care
Published in Hemoglobin, 2014
Ploutarchos Tzoulis, Farrukh Shah, Romilla Jones, Emma Prescott, Maria Barnard
Diabetes is a significant complication of β-thalassemia major (β-TM) and most patients receive fragmented diabetes care. In 2005, we developed a unique Joint Diabetes Thalassaemia Clinic, based at the Department of Diabetes, Whittington Health, London, UK, where patients were reviewed jointly by a multidisciplinary team, including Consultant Diabetologist and Hematologist. Study of the Joint Diabetes Thalassaemia Clinic (2005–2009) showed improvement in glycemic control with fructosamine reduction from 344 umol/L to 319 umol/L over a 1-year period as well as improvement in lipid profiles. The proportion of patients attending the Joint Clinic who achieved metabolic targets compared to the National Diabetes Audit for England was higher for glycemic control (73.0 Joint Diabetes Thalassaemia Clinic vs. 63.0% nationally), blood pressure control (58.0 Joint Diabetes Thalassaemia Clinic vs. 30.0% nationally) and cholesterol control (81.0 Joint Diabetes Thalassaemia Clinic vs. 78.0% nationally). Five patients (22.7%) had microvascular complications. A significant proportion of our patients had endocrinopathies (86.0% hypogonadism, 18.0% hypothyroidism, 23.0% hypoparathyroidism). The unique partnership of our Joint Diabetes Thalassaemia Clinic, allowed these very complex patients to be managed effectively.
Related Knowledge Centers
- Beta
- Globin
- Hemoglobin
- Delta
- Hemolytic Congenital Anemia
- Hemoglobinopathies
- Recessive