The EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies have been recently published as a result of the EMQN haemoglobinopathies best practice meeting, which took place in Leiden, 5–6 September 2012, and was jointly organised and financed by The European Molecular Genetics Quality Network and EuroGentest.

Abstract:

Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. Carrier identification and prenatal diagnosis represent valuable procedures that identify couples at risk for having affected children, so that they can be offered options to have healthy offspring. Molecular diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and patients (especially ‘atypical’ cases who often have complex genotype interactions). However, the haemoglobin disorders are unique among all genetic diseases in that identification of carriers is preferable by haematological (biochemical) tests rather than DNA analysis. These Best Practice guidelines offer an overview of recommended strategies and methods for carrier identification and prenatal diagnosis of haemoglobinopathies, and emphasize the importance of appropriately applying and interpreting haematological tests in supporting the optimum application and evaluation of globin gene DNA analysis.

Cite the article:

Traeger-Synodinos J, Harteveld CL, Old JM, Petrou M, Galanello R, Giordano P, Angastioniotis M, De la Salle B, Henderson S and May A on behalf of contributors to the EMQN haemoglobinopathies best practice meeting. EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies. Eur J Hum Genet. 2014 Jul 23. doi: 10.1038/ejhg.2014.131

Sickle cell disease (SCD) affects ~90,000 people in the U.S. who suffer significant neurological, lung, and kidney damage, as well as severe chronic pain episodes that adversely impact on quality of life. While current medical therapies for SCD can reduce short-term morbidity, the inevitable progressive deterioration in organ function results in a significant decrease in quality of health with early mortality. Allogeneic hematopoietic stem cell transplant (HSCT) can benefit patients with SCD, by providing a source for life-long production of normal red blood cells. However, allogeneic HSCT is limited by the availability of well-matched donors and immunological complications, especially for the more than 80% of patients who lack an HLA-identical sibling donor. Autologous HSCT using a patient's own bone marrow stem cells that have been corrected by transfer of a modified human beta-globin gene that inhibits polymerization of the HbS (stem cell gene therapy) may provide a better therapeutic alternative, as it would avoid the immunologic complications and donor limitations of allogeneic HSCT.

Up to 6 subjects with SCD lacking matched sibling donors and meeting eligibility criteria for disease severity and adequacy of organ function will be enrolled. Following informed consent, enrolled subjects will be screened to confirm full eligibility for participation. Eligible subjects will undergo bone marrow harvest (with a portion cryopreserved as "back-up") with the remaining portion of marrow used to prepare the gene-modified Final Cellular Product: autologous bone marrow CD34+ cells transduced ex vivo by the Lenti/βAS3-FB lentiviral vector to express an anti-sickling (βAS3) gene. The subject will receive marrow cytoreduction with busulfan prior to infusion of the gene-modified cells. The follow-up period will include an initial 2 years of active end-point evaluations, where the subjects will be seen at intervals of no more than 3 months, followed by offer for enrollment into a long-term follow-up study during years 3-15.

The primary objectives of the Phase I study are to assess safety and feasibility, with secondary objectives to assess efficacy (engraftment, βAS3-globin gene expression, and effects on RBC function and clinical hematologic and disease parameters).

More information: clinicaltrials.gov, ITHANET Clinical Trials

An expert panel has recommended expanded adoption of the drug hydroxyurea for the care of people with sickle cell disease, according to a report issued last month. The report also suggests that clinicians give periodic blood transfusions to children with the disease to reduce stroke risk. According to the panel, both treatments are underutilized.

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, convened the panel to review the evidence and make recommendations relating to care available to those with this inherited blood disorder. The report, Evidence-Based Management of Sickle Cell Disease, Expert Panel Report, 2014, gathers the latest sickle cell prevention and treatment information into one document.

Along with those recommendations, the report emphasizes the need for consistent, high-quality health maintenance for people with sickle cell disease. Examples of health maintenance recommendations include the regular use of penicillin through age 5 to reduce the chance of deadly infections, and the importance of pneumococcal vaccines for children and adults.

More information: NIH announcement, Expert Panel Report

Children with sickle cell disease (SCD) are at risk for neurobehavioral problems because of the impact the disease can have on the central nervous system. Specific impairments in working memory are particularly prevalent in school-aged children with SCD. Working memory is more strongly associated with school readiness and academic success than intellectual ability in the general population. The adverse effects of low socioeconomic status (SES) and poverty on cognition and neurodevelopment emerge early, before children have entered formal education. In addition, they affect language and executive function skills (e.g., working memory) more than other skills. SES is a proxy variable for other risk factors. Higher SES is associated with less parental stress, more supportive parenting practices, and better cognitive stimulation based on the availability of books, computers, and outings.

The primary objective of this study is to examine working memory and school readiness in young children with sickle cell disease in comparison to demographically matched control children without sickle cell disease. In addition, this study will examine the relationships of family/environmental factors (caregiver stress, parental responsiveness, and cognitive stimulation in the home) and disease severity to working memory and school readiness skills in preschool-aged children with SCD.

More information: clinicaltrials.gov, ITHANET Clinical Trials