الفهرس 
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Abstract
SUMMARY
T
halassemia is a group of blood diseases caused by one or more gene defects leading to production of abnormal hemoglobin (Hb) which lose its oxygen carrying capacity in variable degrees giving a wide range of the clinical phenotypes of this inherited form of anemia. The term β-thalassemia intermedia (β-TI) was suggested to describe patients who had clinical manifestations that are too severe to be termed minor thalassemia yet too mild to be termed major thalassemia. However, there remains substantial overlap between the three conditions.
The main objective of this study was to evaluate the variable clinical phenotypes among Egyptian pediatric patients with TI, and to study the phenotype – genotype correlation with the encountered β- chain mutations.
A cross-sectional study included 37 children and adolescents diagnosed clinically as having TI and following up regularly in the Pediatric Hematology clinic – Ain Shams University, were enrolled in the current study after fulfilling the inclusion criteria and obtaining consents from their parents. Detailed clinical evaluation sheets were done for patients including full medical history with revision of hospital records. Transfusion history was reported including onset, frequency, intervals, mean pre-transfusion Hb level, and transfusion index. Treatment lines including chelation therapy, L-carnitine and hydroxyurea, history of splenectomy, complications and hospital admission were added. Full clinical examination including weight and height standard deviations and hepato-splenomegaly were reported. Routine laboratory investigations as initial complete blood pictures, hemoglobin electrophoresis and iron studies were recorded from patients’ files. Molecular study was performed by polymerase chain reaction (PCR) to detect the encountered β-thalassemia mutations by β-globin Strip Assay MED™.
Thirty seven patients included 17 males and 20 females, their ages ranged from 4 to 18 years with a mean of 10.3 ± 4.55 years. A family history of thalassemia was present in 20 patients (54.1%) and 14 patients (37.8%) were born to consanguineous parents. The mean age at diagnosis was 4.14 ± 1.77 years ranging between 2 to 8 years old. The mean Hb level at diagnosis was 6.38 ± 1.26 g/dL ranging from 4 – 10 g/dL. Twenty two patients (59.5%) were transfusion independent (NTDT) while 15 patients (40.5%) were transfusion dependent (TDT) with an average transfusion index 70 ml/kg/year. Splenomegaly was present in 10 patients (27%) and splenectomy was done in 5 patients (13.5%).
Dividing 37 patients by the transfusion dependency into two groups was done; NTDT group (Non transfusion dependent thalassemia) contained 22 patients (59.5%) while TDT group (Transfusion dependent thalassemia) contained 15 patients (40.5%).
According to the molecular study, 14 patients (37.8%) were homozygotes, 14 patients (37.8%) were compound heterozygotes and 9 patients (24.4%) were heterozygotes for β- thalassemia alleles. IVS 1.6 (T>C) was the commonest allele detected in 20 patients and 31 alleles (47.7%), followed by IVS 1.110 (G>A) detected in 7 patients and 8 alleles (12.31%), followed by IVS 1.1 (G>A) and CD27 knossos (G>T), each was detected in 6 patients and 6 alleles (9.23%). IVS 1.6 (T>C), IVS 1.110 (G>A) and IVS 1.1(G>A) accounted together for 69.24% of the total detected mutations in this study. Other detected mutations with lower frequencies were IVS 2.745 (C>G), IVS 2.848 (C>A), -87 (C>G), IVS 2.1 (G>A), CD 39 (C>T), CD8 (-AA) and CD 6(A>T) (HbS).
These detected mutations were divided by their molecular genotypes into three main groups; β+β+ was the most common genotype detected in 20 patients (54%), either homozygotes or compound heterozygotes for mild β+ thalassemia mutations; of which 11 patients had NTDT (55%) and 9 patients had TDT (45%), followed by β+β/β°β heterozygotes in 8 patients (21.6%); of which 7 patients had NTDT (87.5%) and one patient had TDT (12.5%), then β°β+ genotype present as compound heterozygotes for one mild and one severe β-thalassemia mutations, detected in 5 patients (13.5%); of which 2 patients had NTDT (40%) and 3 patients had TDT (60%) Another genotype; HbS/β-thalassemia was detected in a lower frequency as 3 patients (8.1%) were compound heterozygotes and one patients (2.7%) was heterozygote.
Our results revealed a significant correlation between the genotype of the patients and mean Hb level, MCH, HT% and LDH, as β+β / β°β patients had higher Hb level, MCH, HT% and lower LDH compared to other patients. We also detected that Hb F and Hb A2 levels were the least and Hb A level was the highest in those with β+β/β°β compared to β+β+ and β°β+ patients.