Screening for beta-thalassaemia carriers in Egypt: significance of the osmotic fragility test.

To estimate beta-thalassaemia carrier rate and to determine an accurate mass screening test, we tested 1000 randomly selected children aged 5-16 years from different geographical areas of Egypt. Microcytosis was present in 412 participants. The osmotic fragility test was positive in 81.1% of the 90 beta-thalassaemia carriers; in the indeterminate group (12 participants), the test was positive in 83.3%; in the 310 who were iron deficient, the test was positive in 63.9%. beta-thalassaemia carrier rate was > or = 9%. Serum iron, microcytosis, HbA2 level and transferrin saturation were accurate tests for detecting carriers. For the one-tube osmotic fragility test, sensitivity was 87.0% and specificity 34.1%; the test has limited use for a mass screening programme in Egypt, where iron deficiency is prevalent.

Screening for beta-thalassaemia carriers in Egypt: significance of the osmotic fragility test

To estimate beta-thalassaemia carrier rate and to determine an accurate mass screening test, we tested 1000 randomly selected children aged 5-16 years from different geographical areas of Egypt. Microcytosis was present in 412 participants. The osmotic fragility test was positive in 81.1% of the 90 beta-thalassaemia carriers; in the indeterminate group [12 participants], the test was positive in 83.3%; in the 310 who were iron deficient, the test was positive in 63.9%. beta-thalassaemia carrier rate was >/= 9%. Serum iron, microcytosis, HbA2 level and transferrin saturation were accurate tests for detecting carriers. For the one-tube osmotic fragility test, sensitivity was 87.0% and specificity 34.1%; the test has limited use for a mass screening programme in Egypt, where iron deficiency is prevalent

Enzyme replacement therapy and bony changes in Egyptian paediatric Gaucher disease patients.

BACKGROUND: In Gaucher disease, the infiltration of the bone marrow by glucocerebroside-laden macrophages (Gaucher cells) triggers a diverse pattern of skeletal disease that results in crippling complications. Reliable ascertainment of the severity and pattern of skeletal disease is essential to determine disease status and the response to enzyme replacement therapy (ERT). Although there is ample documentation of reversal of haematological and visceral disease by ERT, there is a paucity of data on skeletal response to ERT in children. AIM: To delineate the pattern of bone disease in children with Gaucher disease in Egypt and to evaluate its response to ERT. METHOD: Twenty-two children with Gaucher disease were treated with ERT. Phenotyping by clinical, laboratory and radiological criteria was performed at baseline and following 11.2 +/- 4 months of ERT. Genotyping for glucocerebrosidase (GBA) mutations was performed by gene sequencing, and genotype-phenotype correlations were performed.Results. Two-thirds of the patients were from consanguineous pedigrees and 14/22 patients were homozygous or compound heterozygous for L444P and D409H mutations. Bone involvement was detected by plain radiology in 11 children (50%) and in 16 (73%) by magnetic resonance imaging (MRI). There was no correlation of severity of bone involvement and GBA genotype. ERT ameliorated bone disease: 10 of the 11 children with abnormal radiographic findings at baseline showed improvement in skeletal lesions; while 9/16 showed improvement of marrow disease by MRI. Radiographic sensitivity and specificity were 62% and 82% compared to MRI for detection of bone involvement in this patient population. At baseline, bone pain was present in 5 patients and ERT resulted in complete symptomatic remission in all of them. ERT was associated with significant improvement in growth parameters and amelioration of haematological and visceral involvement. CONCLUSION: Symptomatic and radiological skeletal disease is common in children with Gaucher disease in Egypt. MRI is the most accurate technique for detecting early skeletal involvement. There was no correlation between severity of skeletal involvement and GBA genotype. ERT was effective in ameliorating radiological manifestations of skeletal disease and achieving complete remission of bone pain.

Apoptosis in thalassemia major reduced by a butyrate derivative.

BACKGROUND AND OBJECTIVES: In cases of beta-thalassemia major, apoptosis appears to be greatly enhanced in the early-stage erythroid precursors in the bone marrow leading to ineffective erythropoiesis. L-Carnitine is found to strongly reduce apoptosis in different diseases. We investigated the effect of oral L-carnitine therapy on apoptosis in thalassemia major patients. METHODS: Eighteen thalassemia major patients with a mean age of 12.2 +/- 6.6 years were included. Detection of apoptosis was done by photometric enzyme immunoassay (ELISA) and agarose gel electrophoresis before and after 6 months of oral therapy with L-carnitine (50 mg/kg/day). RESULTS: A significant decrease of apoptosis frequency in the erythroid precursors in the bone marrow of studied cases was noted after therapy. The quantity of nucleosomes measured by ELISA dropped from 3.65 +/- 1.338 to 1.60 +/- 0.65 after therapy (p = 0.005). A positive ladder pattern reflecting apoptosis on agarose gel electrophoresis was detected in 88.9% of cases prior to treatment versus 16.7% after therapy (p = 0.006). Patients also had a significant decrease in the frequency of transfusions and increase in the pre-transfusion hemoglobin levels after therapy. CONCLUSION: L-Carnitine seems to be a good modulator of apoptotic processes in thalassemic patients leading to a decreased frequency of programmed erythroblast death and general improvement of the disease condition.