Prevalence of Xmnl G[gamma] polymorphism in Egyptian patients with beta-thalassemia major

Beta-thalassemia results from a deficiency of beta-globin chains leading to an excess in alpha globin chains resulting in hypochromic microcytic red cells, ineffective erythropoiesis and hemolytic anemia. It is a result of a decline of HbF synthesis during the first year of life. F-cell levels are influenced by a sequence variant [C[right wards arrow] T] at position -158 upstream of the -globin gene, so the frequency of the Xmnl G[gamma] polymorphism in Egyptian patients with beta-thalassemia major needed evaluation to decide on the value of HbF augmentation drugs in treating Egyptian beta-thalessemia. A cross-sectional study including 30 beta-thalassemia major patients diagnosed and attending the Pediatric Hematology Unit, Children's University Hospital, Ain Shams University, Cairo, Egypt, in the period from October 2008 to October 2009. The 17 males and 13 females underwent a medical history and physical examination. Tests included a complete blood count, hemoglobin electrophoresis, serum ferritin, and detection of Xmnl G[gamma] polymorphism by PCR. The mean [SD] age was [2] 10.2 [6.9] years. The most frequent genotype observed was homozygosity for the absence of the site Xmnl [-/-] in 96% of cases. Heterozygosity [+/-] genotype was detected in 4% of cases, while homozygosity for the site Xmnl [+/+] genotype was absent. Genotype was not related to age at first transfusion, fetal hemoglobin level or transfusion frequency. Despite the small sample size, the study demonstrated that Egyptian beta-thalessemia patients have low frequency of positivity for the Xmnl polymorphism whether in heterozygous [+/-] or homozygous [+/+] state

Molecular genetics of hemophilia A: clinical perspectives

Since the publication of the sequence of the factor VIII [F8] gene in 1984, a large number of mutations that cause hemophilia A have been identified and a significant progress has been made in translating this knowledge for clinical diagnostic and therapeutic purposes. Molecular genetic testing is used to determine the carrier status, for prenatal diagnosis, for prediction of the likelihood of inhibitor development, and even can be possibly used to predict responsiveness to immune tolerance induction. Phenotypic heterogeneity of hemophilia is multifactorial, mainly related to F8 mutation but other factors contribute especially to coinheritance of prothrombotic genes. Inhibitor development is mainly related to F8 null mutations, but other genetic and non genetic factors could contribute. This review will focus on the genetic aspects of hemophilia A and their application in the clinical setting and the care of patients and their families

Features of Egyptian type 1 diabetic toddlers clinico-epidemiological study of Egyptian toddlers and preschool children with type 1 Dm

The incidence of type 1 diabetes mellitus is increasing worldwide especially in toddlers and preschool children in whom the disease appears to run a more accelerated course than the elder age group. To determine the epidemiological and clinico-pathological features of type 1 diabetes in Egyptian toddlers and preschool children. 120 diabetic patients were included divided into two groups: according to age at presentation: group I [N = 60], aged < 5 years at presentation [32 males and 28 females] diagnosed in the period from January 1[st] 2006 till December 31[st] 2006; group II [N = 60], aged > 5 years at presentation [30 males and 30 females]. They were diagnosed in the period from January 1[st] 2000 to December 31[st] 2005. Patients were subjected to thorough history, and examination. Laboratory investigations included; random blood sugar [RBS], glycated hemoglobin [HbA[1c]] every 3 months as well as C-peptide assessed initially and after 6 months. Structured questionnaire was filled by parents for assessment of diabetic risk factors. There was a steady increase in the percentage of diabetic toddlers and preschool children in relation to total number of diabetic patients diagnosed in the 6 years period, increasing from 16% in the year 2000 to 23.3% in year 2005. The median duration of exclusive breast feeding was 2 months in patients with early onset versus 4 months in patients with late onset of diabetes. The median duration of total breast feeding was 9.5 months versus 11.2 months in patients with early onset diabetes mellitus and late onset respectively. Median age of introduction of cow milk was 2.5 months in early onset diabetics [range 1-5.3] compared to 4 months in late onset diabetics [range 2-7]. History of preceding clinical infection [febrile illnesses] occurred in 73.3% and 33.3% in diabetic toddlers and older age group respectively [p<0.0001]. 50% of young diabetics were diagnosed in winter and autumn versus 25% of older group [< 0.05]. More aggressive disease presentation in the toddler group as 75% had diabetic ketoacidosis [DKA] as a presenting symptom compared to 38.3% of the older diabetics [p<0.0001]. Higher initial RBS, higher incidence of hypoglycemia attacks in diabetic toddlers compared to older age group [p<0.0001]. Higher mean insulin dose and mean random blood sugar follow up values were found in young diabetics [p<0.01]. Young diabetics had significantly lower initial C-peptide values [p<0.0001] as well as significantly lower 6 months follow up values [p<0.0001] compared to older age. Initial C-peptide values were negatively correlated with initial RBS [r = -0.335; p<0.05] and mean insulin dose [r = -0.609; p<0.0001] while it positively correlated with age at presentation [r = 0.538; p < 0.0001]. The role of environmental factors in triggering type 1 DM was highlighted especially in toddlers with more aggressive presentation and disease course which was related to lower beta-cell reserve

Pattern and prognosis of haematological and non-haematological presentatations of juvenile SLE: five years longitudinal study

To assess the pattern of hematological disorders in juvenile systemic lupus erythematosus [SLE] and its impact on prognosis and survival. The prevalence of SLE in a Pediatric Hematology Unit was also assessed through a five years longitudinal study. A prospective follow up study of 32 SLE patients diagnosed and treated in the Children's Hospital and in the Rheumatology and Rehabilitation Department, Ain Shams University Hospitals, during a period of 5 years was done. Follow up of patients with acquired hematological diseases [n=235] diagnosed in a Pediatric Hematology Unit, in the same period was done to assess the prevalence of SLE in that population. Among the 32 SLE patients, 30 were females and two were males, the mean age at diagnosis was 13.3 +/- 3.5 years. Fifteen patients had an initial hematological presentation. Anemia and thrombocytopenia were the commonest hematological presentation [68.8% and 40.6% respectively]. The main non-hematological presenting features included nephropathy [71.9%], cutaneous manifestations [50%] and arthritis [65.6%]. At presentation, ANA antibodies and anti DNA were positive in 67.7% and 67.8% respectively, reaching values of 90.4% and 86.4% respectively during follow up. As regard fate, 25.2% were in remission, 15.6% lost follow up and 59.4% had progressive disease. Ten children out of the studied 235 patients with acquired hematological diseases [4.3%] developed four or more American College of Rheumatology criteria for the diagnosis of SLE during five years follow up. They were 5 out of 186 children with idiopathic thrombocytopenic purpura [2.7%], 2 out of 12 with autoimmune hemolytic anemia [16.7%], 2 out of 3 with Evan's Syndrome [66.6%] and 1 out of 5 with pure red cell aplasia [20.0%]. None of hypoplastic anemia [n=29] developed SLE. Hematological disorders are common features in childhood SLE with an impact on the prognosis. SLE constitutes the underlying pathology in 4.3% of children with acquired hematological disorders

Bone density in survivors of childhood acute leukemia and malignant lymphomas

This study aimed to assess bone mineral density in survivors of childhood acute leukemia and malignant lymphomas to determine the prevalence of osteoporosis and identify the possible predisposing factors and patients at the greatest risk of reduced bone mineral density. The study included 41 survivors [27 patients had acute lymphoblastic leukemia and 14 patients had malignant lymphomas]. In conclusion, 60.9% of the survivors of childhood leukemias and lymphomas had decreased BMD, osteoporosis being especially severe in 17.1% of these patients. In view of the risk of fractures among patients with osteoporosis, the survivors of childhood malignancy were at an increasing risk of bone fractures later in life irrespective of the underlying cause of osteoporosis, thus the intervention should be considered for prevention and proper management