Haemoglobin Bristol-Alesha in a child with non-spherocytic severe haemolytic anaemia and marked anisochromic poikilocytosis with basophilic stippling and amorphous intracellular content.

Here we describe a retrospective study of a 10-year-old girl, adopted from India, and referred to the Rare Anemias Unit for the diagnosis of a severe haemolytic anaemia of unknown etiology. Blood film examination revealed markedly abnormal red cell morphology characterised by a mixture of very pale (hypochromic) cells with basophilic stippling and macrocytic cells containing coarse basophilic dots and an amorphous material of unknown origin. With a presumptive diagnosis of pyruvate kinase deficiency (PK), the patient had been splenectomised at 7 years of age with a partial recovery of the anaemia and a decrease of the blood transfusion rate.

Concise review: how do red blood cells born, live, and die?

The average life cycle of a human RBC is approximately 120 days. Generally, by this point, the cell is worn out and damaged. RBCs pass through both the spleen and liver, where specialised immune cells called macrophages are found.

A comprehensive update of ICET-A Network on COVID-19 in thalassemias: what we know and where we stand.

A review of the literature on COVID-19 pandemic in patients with thalassemias is presented. Globally, the prevalence of COVID-19 among  β-thalassemia patients seems to be lower than in general population; associated co-morbidities aggravated the severity of  COVID- 19, leading to a poorer prognosis, irrespective of age. A multicenter registry will enhance the understanding of COVID-19 in these patients and will lead to more evidence-based management recommendations.

Preliminary Data on COVID-19 in Patients with Hemoglobinopathies: A Multicentre ICET-A Study.

Objectives: This study aims to investigate, retrospectively, the epidemiological and clinical characteristics, laboratory results, radiologic findings, and outcomes of COVID-19 in patients with transfusion-dependent β thalassemia major (TM), β-thalassemia intermedia (TI) and sickle cell disease (SCD).

Design: A total of 17 Centers, from 10 countries, following 9,499 patients with hemoglobinopathies, participated in the survey.

Main Outcome Data: Clinical, laboratory, and radiologic findings and outcomes of patients with COVID-19 were collected from medical records and summarized.

Thyroid Disorders in Homozygous β-Thalassemia: Current Knowledge, Emerging Issues and Open Problems.

Changes in thyroid function and thyroid function tests occur in patients with β-thalassemia major (TM). The frequency of hypothyroidism in TM patients ranges from 4% to 29 % in different reports. The wide variation has been attributed to several factors such as patients' genotype, age, ethnic heterogeneity, treatment protocols of transfusions and chelation, and varying compliance to treatment.

Density, heterogeneity and deformability of red cells as markers of clinical severity in hereditary spherocytosis.

Hereditary spherocytosis (HS) originates from defective anchoring of the cytoskeletal network to the transmembrane protein complexes of the red blood cell (RBC). Red cells in HS are characterized by membrane instability and reduced deformability and there is marked heterogeneity in disease severity among patients. To unravel this variability in disease severity, we analyzed blood samples from 21 HS patients with defects in ankyrin, band 3, α-spectrin or β-spectrin using red cell indices, eosin-5-maleimide binding, microscopy, the osmotic fragility test, Percoll density gradients, vesiculation and ektacytometry to assess cell membrane stability, cellular density and deformability.

Meeting Report: The Equality Project on Endocrine Complications in Thalassemia: Selected Highlights from the First Turkish Congress, Antalya, 10th-11th December 2018.

Major difficulties reported by endocrinologists /pediatricians/ hematologists in the care of thalassemic patients with endocrine complications were: lack of facilities, correct interpretation of tests, unfamiliarity with medical treatment and the cost of diagnostics and therapeutics. Therefore, there is a felt need to educate and train more endocrinologists/pediatricians/hematologists in this field in order to optimise growth and prevent endocrine complications. To achieve this goal, in 2015, a project called Equality was submitted by three countries (Turkey, Spain and Italy) and approved by the European Union (EU) with the aim to train doctors and nurses, taking care of youth and young adults TM patients, in the prevention, diagnosis, and management of endocrine disorders.

Haemoglobinopathies in Europe: health & migration policy perspectives.

Background: Major haemoglobinopathies (MH), such as thalassaemia syndromes (Thal) and sickle cell disorders (SCD), are genetic defects associated with chronic anaemia and other complications. In Europe, MH are rare diseases (RD) but their prevalence is significantly growing in many countries due to mobility and migration flows. This creates a growing health problem in the EU that has not yet been effectively addressed by Member States (MS) authorities.

Enzymatic and metabolic characterization of the phosphoglycerate kinase deficiency associated with chronic hemolytic anemia caused by the PGK-Barcelona mutation.

Recently, we reported a new mutation of phosphoglycerate kinase (PGK), called PGK-Barcelona, which causes chronic hemolytic anemia associated with progressive neurological impairment. We found a 140T→A substitution that produces an Ile46Asn change located at the N-domain of the enzyme and we suggested that the decrease of the PGK activity is probably related to a loss of enzyme stability. In this paper, by analyzing whole hemolysates and cloned enzymes, we show that both enzymes possess similar kinetic properties (although some differences are observed in the Km values) and the same electrophoretic mobility.

Epidemiology of rare anaemias in Europe.

Registry and epidemiological data of Rare Anaemias (RA) in Europe is in general still incomplete and/or partially documented. One important issue is the increasing prevalence of haemoglobin disorders (HD) due to migrations from high prevalence areas. The size of the problem, particularly for sickle cell disease (SCD), is already having an impact on health services in many European countries.

Molecular heterogeneity of beta-thalassemia alleles in Spain and its importance in the diagnosis and prevention of beta-thalassemia major and sickle cell disorders.

In the last 20 years, migratory flows have changed the pattern of beta-thalassemia (beta-thal) mutations in Catalonia and have also increased beta(S) prevalence, either alone or in association with beta-thal alleles. Characterization of the beta gene is needed for genetic counseling for beta-thal major and also for sickle cell diseases. The purpose of this study was to investigate the current distribution pattern of beta-thal mutations.

Neonatal haemoglobinopathy screening in Spain.

The prevalence of variant haemoglobins in Spain is increasing as a result of recent African immigration. Of the 19 regions of Spain, 13 have more than 1% of residents of African origin or ethnicity. Haemoglobinopathy prevalence is heterogeneous.

New haplotype for the Glu104Asp mutation in triose-phosphate isomerase deficiency and prenatal diagnosis in a Spanish family.

First-trimester prenatal diagnosis was undertaken by chorionic villus DNA analysis in a Spanish family with the inherited Glu104Asp triose-phosphate isomerase deficiency. The fetus was heterozygous for the mutation and therefore predicted to be clinically unaffected. To investigate the evolutionary origin of this mutation, studies were conducted on the intragenic 2262A/G polymorphism and the CD4 pentameric tandem repeat marker.

Phosphoglycerate mutase BB isoenzyme deficiency in a patient with non-spherocytic anemia: familial and metabolic studies.

We previously reported the first case of red blood cell phosphoglycerate mutase (PGAM) isozyme BB deficiency due to the homozygous point mutation cDNA 690G->A, which causes a substitution of methionine 230 by isoleucine. In the present work we analyzed the changes in glycolytic intermediates caused by this mutation. With the exception of hexose phosphates, all other intermediates were decreased.

Red cell adenylate kinase deficiency: molecular study of 3 new mutations (118G>A, 190G>A, and GAC deletion) associated with hereditary nonspherocytic hemolytic anemia.

We report here 2 patients with chronic nonspherocytic hemolytic anemia (CNSHA) and severe red blood cell (RBC) adenylate kinase (AK) deficiency. One of these patients, a boy of Spanish origin, exhibited a neonatal icterus and splenomegaly and required blood transfusions until the age of 2 years. The other patient was a white, American infant born to parents who were first cousins; he also presented with neonatal icterus and anemia.

Hereditary non-spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies.

In four unrelated patients with chronic haemolysis and markedly reduced red blood cell (RBC) glutathione (49.5%, 12.6%, 11.

Evaluation of the blue formazan spot test for screening glucose 6 phosphate dehydrogenase deficiency.

Several screening tests for glucose 6 phosphate dehydrogenase (G6PD) deficiency have been reported thus far, and a standardized method of testing was proposed by the International Council for Standardization in Hematology (ICSH). The screening test used in any particular laboratory depends upon a number of factors such as cost, time required, temperature, humidity, and availability of reagents. In this study, a direct comparison between three different G6PD screening methods has been undertaken.

alpha-Thalassaemia due to a single codon deletion in the alpha1-globin gene. Computational structural analysis of the new alpha-chain variant. Mutations in brief no. 132. Online.

A new unstable alpha-globin chain associated with alpha-thalassemia phenotype has been found in a Spanish patient. Molecular analysis of the alpha-globin gene complex using PCR and non-radioactive single-strand conformation analysis, allowed to identify a new mutation in the second exon of the alpha-globin gene. Direct sequencing of the abnormal fragment revealed a 3 bp deletion, which led to the loss of a single codon corresponding to a Lys (K) residue at position 60 or 61 DK60 or DK61.

Molecular genetics of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Spain: identification of two new point mutations in the G6PD gene.

In order to explore the nature of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Spain, we have analysed the G6PD gene in 11 unrelated Spanish G6PD-deficient males and their relatives by using the polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) analysis combined with a direct PCR-sequencing procedure and PCR-restriction enzyme (RE) analysis. We have identified eight different missense mutations, six of which have been reported in previously described G6PD variants. In nine patients who had presented with acute favism we found the following mutations: G6PD A-376G-202A (four cases), G6PD Union1360T (two cases), G6PD Mediterranean563T (one case) and G6PD Aures143C (one case).

Orthostatic and exercise-induced advanced nodal atrioventricular block.

A 69-year-old woman was referred for asthenia and dizziness when walking in the last two months. No clinical abnormalities were found, and sinus rhythm was present when lying down. On orthostatism and walking, advanced AV block developed.