Study of the effect of HFE gene mutations on iron overload in Egyptian thalassemia patients

HFE gene mutations have been shown to be responsible for hereditary hemochromatosis. Their effect on iron load in [3-thalassemia patients and carriers remains controversial. We aimed to determine the prevalence of HFE gene mutations [C282Y and H63D] in [3-thalassemia patients and carriers and to investigate its effect on their serum ferritin levels. A total of 100 [3-thalassemia subjects; 75 patients and 25 carriers were screened for HFE gene mutations by PCR-RFLP. Serum ferritin measured by ELISA was evaluated in relation to HFE mutations. Twenty-eight [3-thalassemia patients [37.3%] were heterozygotes for H63D mutation [H/D], 8 [10.7%] were D/D and 39 [52%] were negative [H/H]. Among carriers, 4 [16%] were D/D and 21 [84%] were H/H homozygotes. C282Y mutant allele was not detected in any of the subjects. Serum ferritin levels were significantly higher in p-thalassemia patients heterozygotes or homozygotes for H63D mutation compared to those without mutation [p = 0.000]. Carriers homozygotes for H63D mutation showed significantly higher serum ferritin levels compared to those without mutation [p < 0.001]. Homozygosity for H63D mutation tends to be associated with higher ferritin levels in beta-thalassemia patients and carriers suggesting its modulating effect on iron load in these cases

Osteoporosis in beta-thalassemia major patients: role of COLIA1 gene G-T polymorphism

Growth impairment and osteoporosis are serious causes of morbidity in patients with beta-thalassemia major [beta-TM]. Desferoxamine [DFO] toxicity and iron overload have been proposed as the main underlying reasons. G-T polymorphism in regulatory region of COLIA1 gene has recently been associated with reduced bone mass and osteoporotic fractures in postmenopausal women. To detect the possible implication of COLIA1 gene polymorphism in pathogenesis of osteoporosis in beta-TM. Twenty five patients with beta-TM and 20 healthy controls were investigated for the G-T polymorphism of COLIA1 gene using restriction enzyme analysis. Bone mineral density [BMD], growth parameters, serum ferritin level and duration of chelation therapy were also assessed. We detected a heterozygous polymorphism of COLIA1 gene in 12% of beta-TM patients and 25% of the control group. Thalassemic patients had significant lower BMD than normal controls [p < 0.01]. Significant correlation was observed between low BMD and both duration of DFO intake and high ferritin level. Within the control group: Subjects with G/T genotype had significantly lower femoral and lumber BMD than those with G/G genotype. In thalassemic patients: No significant difference was found in BMD between the two COLIA 1 genotypes. We cannot detect evident role for COLIA1 gene polymorphism in the pathogenesis of osteoporosis in this group of beta-TM patients although this role has been detected in the control group. Further studies that include higher number of patients and more than one genetic polymorphism are needed in order to evaluate the role of genetic factors in the pathogenesis of osteoporosis in thalassemic patients

effect of hydroxyurea in the management of Pediatric Sickle cell patients

Low levels of fetal hemoglobin [HbF] in sickle cell disease [SCD] patients [pts] are associated with a variety of vaso-acciusive complications and an increased risk of early death. Raising HbF levels can reduce the effect of the disease. Hydroxyurea [HU] reduces the production of HbS containing red cells and favours the production of HbF containing red cells. It has been used successfully in the management of adults with SCD and there is growing data on its efficacy and safety in pediatric age group. This study reviews our clinical experience with HU in the treatment of pediatric pts with SCD attending the Pediatric Hematology Clinic of Cairo University. Sixty SCD pts from 2001 to 2007 who received HU over the period of 6 years [yrs] and who continued therapy for at least 6 months were included. Four pts were excluded because of noncompliance to treatment. Response to HU was assessed both clinically and by laboratory findings. Pts were considered responders if they showed >/= 50% improvement in clinical and laboratory data. These data included number of blood transfusions/yr, vasoocciusive crisis [VOC]/yr requiring admission to the emergency unit, hospital admissions/yr. Laboratory data included Hb [g/dl], MCV [fl], HbF%, total leucocytic count [TLC], x10[3]ml absolute neutrophil count [ANC], platelets x10[3]ml and reticulocytic count [%] and serum ferritin level [ng/ml]. Fifty six pts [44 children and 12 adults [>18 yrs] were included. Their mean age was 14.05 +/- 5.3 yrs [range of 6-28 yrs]. Thirty seven were females and 19 males. Twenty four [42.9%] were sickle-beta thalassemia while 32 [57.1%] were homozygous sickle cell anemia [SS]. The main indications for starting HU therapy were frequent VOC, transfusion dependency and acute chest syndrome [91%, 86% and 16% respectively]. Other indications included hepatic crisis [5%], bone infarction [7%], sequestration crisis [5%] and pulmonary hypertension in one case. HU was started in a dose of 15mg/kg/day with careful monthly monitoring for side effects. There was no attempt to achieve maximum tolerated dose. Dose increase or decrease was done depending on clinical and laboratory response with a maximum dose of 30mg/kg/day. The mean dose of HU was 15.8mg/kg/day [range 10-30 mg/kg/day] and the mean duration of therapy was 3.25 yrs [range of 0.5-6 yrs]. Forty four pts [78.6%] were found to be responders. There was a significant [p<0.05] improvement in all clinical parameters. Responders showed a significant decrease in TLC, ANC, reticulocytic count and serum ferritin [P values 0.002, 0.019, 0.000, 0.001 respectively]. Significant increase in HbF and MCV [p=0.000, 0.001 respectively] was also observed. HU toxicity was defined by>3 fold increase in ALT, platelet count<80,000 p1, ANC<1500 or increase in serum creatinine>50%above baseline. Twenty pts [35.7%] showed signs of HU toxicity: elevated ALT [n=9], neutropenia [n=7], thrombocytopenia [n=1], unexplained jaundice [n=1] and both neutropenia and jaundice [n=2]. Thirteen pts continued therapy with reduction of the dose or temporary stopping of HU while 7 stopped HU. It was noticed that all pts who developed hepatotoxicity were HCV positive p=0.036]. It was also shown that hepatotoxicity was significantly higher among those receiving Deferiprone with HU [n=20] [p=0.001]. There was no relation between response to HU and patients' age, sex, spleen status or phenotype. HU provides the best available strategy to achieve clinical and hematological improvement in SCD in pediatrics, but requires periodic monitoring of blood count and ALT levels especially for HCV positive pts and those on Deferiprone therapy

Audiologic assessment of beta-thalassemia major children under combined versus single agent chelation therapy

Beta-thalassemia major [BTM] is an inherited blood disorder which leads to life threatening anaemia and requires regular blood transfusions andironchelating therapy throughout life from early childhood. Parenteral chelation therapy with desferrioxamine [DFO] is well established, however, poor compliance with the rigours of parenteral treatment limits its regular use. The orally active iron chelator deferiprone [LI] has been shown to be as effective as DFO in some patients. The improvement of iron status resulting from the combined use of both LI and DFO due to [he additive effects of both drugs and the lack of toxicity caused by combining the drugs, however, suggest that this is a promising new method of iron chelation. This study was undertaken to assess the audiologic test results of combined [LI and DFO] therapy versus single agent [LI or DFO] therapy for reducing transfusional iron overload, and to evaluate the safety of the oral chelator Deferiprone [LI] on the auditory system. Sixty six beta thalassemia major children were included in this study. They were randomly classified into 3 arms: Patients in arm A were under combined DFO and LI chelation therapy. Patients in arm B were under LI therapy and patients in arm C were under DFO therapy. All patients were subjected to full history taking and laboratory investigations. Audiologic evaluation was performed at the beginning of the study [baseline evaluation] and at the 1 year follow-up [termination of the study] and consisted of puretone audiometry [PTA], extended high frequency audiometry, unmittance metry, otoacoustic emission [OAE]; transient evoked OAE [TEOAE] and distortion product OAE [DPOAE] and Auditory brainstem response [ABR]. Patients in arms A and B exhibited an improvement in their PTA and OAE results at the 1 year follow-up period. While patients in arm C presented with deterioration 11 their hearing sensitivity and cochlear function especially it the high frequencies. There was no association between hearing loss, serum ferritin level, age and Hb level. Patients under combined therapy exhibited slightly higher [better] TEOAE and DPOAE results than patients under LI therapy although this did not reach statistical significance. ABR results revealed no significant difference between the 3 arms in the absolute and interpeak latencies of waves I, III and V at the 1 year follow-up period. DFO ototoxicity is more cochlear than ret-rocochlear and is more pronounced at the base of the cochlea and appears to be reversible if diagnosed early. DFO ototoxicity appears to be subject to individual susceptibility. Combined [DFO and LI] therapy and LI chelation therapy preserve cochlear and retrocochlear function. However, combined therapy proved to be slightly superior to LI therapy in preservation of cochlear function in addition to its superior chelating ability. It is recommended that thalassemic patients [especially those under DFO therapy] should undergo regular audiologic assessments by OAEs and should revert to combined [DFO and LI] therapy if cochlear impairment is detected. Deferiprone [LI] appears to be safe on the auditory system,however, its long-term effect still needs to be explored

Molecular screening for G6PD gene mutations in children with glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase [G6PD] deficiency is a heterogeneous enzyme abnormality with a high frequency among people of African, Mediterranean and Southeast Asian origins. In almost every group studied in the Middle East, only three to four different G6PD mutations were detected. Among these, the G6PD Mediterranean mutation [563C -> T] was by far the most common. Apart from this mutation, little is known about the genetic heterogeneity of G6PD deficiency in Egypt. To screen for G6PD gene mutations in a group of Egyptian children with G6PD-deficiency who were previously screened for the Mediterranean [563C -> T] mutation. This work was conducted on twenty-one unrelated Egyptian children [17 males and 4 females] presenting with G6PD deficiency previously screened for the G6PD Mediterranean mutation [563C -> T]. Carefully-preserved DNA of patients refrigerated at -20°C and DNA of 21 age-matched normal subjects extracted from blood leukocytes by saltingout technique were screened for mutations in the G6PD gene by PCR-single strand conformation polymorphism [SSCP] analysis followed by DNA sequencing. In addition to the G6PD Mediterranean mutation 563C -> T previously identified by PCR-RFLP analysis in 6/21 male patients [28.6%], a further of 2 different mutations; G6PD A- mutation and G6PD Chatham were observed in 2/21 [9.5%] and 1/21 [4.8%] patients respectively. Twelve patients [57.1%] remained uncharacterized at the genetic level, a normal African G6PD A genotype was detected in one patient of them. Patients with G6PD Mediterranean mutation were more susceptible to hemolysis than were patients with G6PD A- and G6PD Chatham mutations. The lower prevalence of G6PD Mediterranean mutation in our patients and the finding of three different mutations in a relatively small number of G6PD-deficient subjects reflect the considerable genetic heterogeneity of G6PD deficiency of the Egyptian population

Detection of HCV RNA in saliva of Egyptian children receiving frequent blood transfusions

Hepatitis C virus [HCV] infection is considered a major public health problem allover the world, especially Egypt. Blood is almost the only route for HCV diagnosis. It has been reported that HCV could be detected in other body fluids including saliva which represents an easier route than blood especially in infants and children. This study aimed to: 1] Assess the prevalence of HCV infection among high risk group of Egyptian children. 2] Evaluate the detection of HCV antibodies [anti-HCV] and HCV RNA in saliva against their detection in serum among HCV positive children. This study included 200 children [92 males and 108 females] who were attendants of Haematology Clinic at Abu El-Reish Hospital, Cairo University, for receiving frequent blood transfusions. Serum and saliva samples were analyzed for detection of anti-HCV by ELISA technique and for HCV RNA by a home made RT-PCR method. Liver function tests were performed also. Results of serum samples revealed that 134/200 [67%] children were anti-HCV seropositive, out of them 79/134 [59%] children had HCV RNA in their sera. Saliva samples of HCV infected children [n=79] showed that 53/79 [67.1%] and 31/79 [39.2%] were anti-HCV and HCV RNA positive respectively. Prevalence of HCV infection was 39.5% of 200 studied children [67% of 134 anti-HCV positive children]. It could conclude that: 1] Prevalence of HCV infection among the studied children is considered high. 2] Saliva could play a possible role of biological fluids as a non parenteral route of intrafamilial spread of HCV infection. 3] More sensitive techniques could be developed to use saliva as a reliable route for HCV detection

Correction of Aberrant pre mRNA splicing using antisense oligonucleotides in B thalassemia patients with known IVS-I,nt 110 mutation

1VS In l 110 mutation is the most common mutation in Egyptian thalassemics. The mutation causes aberrant splicing ofpre-mRNA resulting in labile RNA causing deficient B-globin chain synthesis. Antisense oligonucleotide strategy is one of the more simple technique in gene therapy. Using oligonucleotides covering the aberrant splice site gives chance for normal splicing and correction of the anomaly at the RNA level. Blocking of aberrant splicing at IVS 1nt 110 site of B-globin pre-mRNA using antisense oligonucleotides results in subsequent restoration of normal mRNA production in B-thalasseamia patients with IVS 1nt 110 mutation This study involved 10 patients with known IVS IntllO mutation; 6 homozygous and 4 heterozygous patients peripheral blood mononuclear cells were separated and duplicate liquid culture systems were set using erythropoietin and stem cell factor with and without antisense oligonucleotides [20 micro. mol/ml]. Correction of aberrant splicing was evaluated by estimation of total hemoglobin, hemoglobin F, and a reverse transcriptase polymerase chain reaction followed by agar gel electrophoresis was used to amplify and detect both aberrant mRNA and normal mRNA in duplicate samples. Five cases [50%] showed correction after antisense oligonucleotide treatment, two cases showed the appearance of normal mRNA band with absence of aberrant band and in 3 cases an increased ratio of normal mRNA band to aberrant band was found [from 2:1 to 3:1 in two cases and from 2:1 to 4:1 in the third case]. The 5 corrected cases showed significant increase in total Hb which varied between 4 to 6 folds increase. Antisense oligonucleotide treatment corrects splicing ofpre-mRNA leading to appropriate expression of B-globin mRNA which may pave the way for treatment of thalassaemia.

Evaluation of growth hormone in polytransfused thalassemic patients with short stature and effect of L - carnitine treatment

Objective: Evaluation of growth hormone in poly- transfused thalassemic patients with short stature and effect of L-carnitine therapy in patients with growth hormone deficiency

Method: The study included. 30 beta-thalassemic patients with mean age 13.8 +/-1.7 yr and 30 children with constitutional short stature as a control. Anthropometric measurements, thyroid profile, insulin like growth factor -1 [IGF-1] and growth hormone [GH] provocation by 2 tests were done at the beginning of the study. Anthropometric measurements and pubertal assessment were done for all patients after 6 months. Eight patients with inadequate GH response to both clonidine and ITT were given L-Carnitine treatment at a dose of 50 mg/kg/day divided into three doses for 6 months. They were reevaluated after 6 months of therapy

Results: Twelve [40%] patients had sub-clinical hypothyroidism [diagnosed by normal free thyroxin level and elevated thyroid stimulating hormone], 10 [33.3%] patients had growth hormone deficiency. Peak GH and growth velocity /{cm and Standard Deviation Score [SDS]] were significantly lower while weight [SDS] and weight / height SDS were significantly higher than patients with constitutional short stature [P < 0.05]. A significant positive correlation was found between height and target height [cm]. Eight patients with growth hormone deficiency were given L-carnitine for 6 months [50 mg/Kg/day]. After L-carnitine treatment hemoglobin level, peak GH, IGF-1 and growth velocity [cm and SDS] were significantly increase and the number of blood transfusions was significantly decrease [p<0.05]. Delta changes were higher in height [cm and SDS], estimated mature height, sitting height and lower in target height - height [SDS and cm] six months after L-carnitine treatment in beta-thalassemic patients with growth hormone deficiency [p <0.05]

Conclusion: Growth hormone[GH] deficiency is an etiologic factor in beta-thalassemia patients with short stature. L-Carnitine can promote GH secretion and growth

Evidence of diastolic Dysfunction and pulmonary hypertension in sickle cell anemia: possible role of L-carnitine treatment

The aim of this work was to assess cardiac status and pulmonary blood pressure in Egyptian sickle cell disease [SCD] pediatric patients. Possible role of L-carnitine in the amelioration of heart complications was also studied. This study was conducted on 37 pediatric patients with sickle cell disease, their mean age was 9.4 +/- 3.6 years. They were subjected to complete history taking, general examination, laboratory investigations [complete blood count and serum ferritin] and echocardiographic examination including measurement of cardiac chamber dimensions, systolic and diastolic functions of left ventricle and estimation of pulmonary artery systolic pressure [PASP]. The echocardiographic findings showed a significant increase in left atrial dimensions in SCD patients compared with the normal controls, which decreased after L-carnitine therapy but did not reach a significant difference. Other cardiac dimensions revealed no significant difference between the patients and control group. Systolic functions of left ventricle did not show any significant difference between patients and controls. Diastolic dysfunction was found in all patients. Diastolic parameters revealed a significant improvement by a decrease in E-wave peak velocity and E/A ratio after L-carnitine therapy. Pulmonary hypertension was found in 17 cases and showed a significant decrease after L-carnitine therapy. The clinical and laboratory re-evaluation of the patients after the period of therapy revealed a significant increase in weight and height of the patients together with a significant decrease in the frequency of blood transfusion and serum ferritin levels

Phenotypic scoring in thalassemia intermedia and the impact of underlying molecular defects

Thalassemia intermedia encompasses clinical conditions ranging in severity from, thalassemia carrier sate to transfusion dependent major like. Therefore, classification of patients in useful for proper counseling, management and prenatal diagnosis. We followed a special scoring system for classification of 155 beta-thalassemia intermedia patients. According to this system the patients were classified into mild [23.2%], moderate [27.7%] and severe [49.1%]. Molecular studies for detection of mutations were done for 66 of the cases using Reverse Dot Blot [RDB] and Amplification Refractory Mutation System [ARMS] techniques. Genotypes were compared with the clinical classifications. The mild beta[++]/beta[++] genotype was detected in 38.8% of the mild, 45% of the moderate and 21% of the severe group. We concluded that, the clinical scoring of severity of thalassemia intermedia is useful to develop management guidelines for the subgroups and that severity could not be always explained by the underlying genotype. Search for other mechanisms or modifying factors is needed for proper prognosis, genetic counseling and future

Study of blood levels of glucose and insulin in Egyptian thalassemics not known to be diabetics

This study was conducted on 32 patients [19 females and 13 males] with thalassemia major aged 2-18 years [mean 11.8 years] and 10 age matched controls. They were subjected to full history taking, clinical examination, fasting and postprandial glucose levels as well as estimation of fasting and postprandial insulin levels. The results showed that fasting and postprandial blood glucose levels were significantly higher in thalassemics compared with the controls. Fasting and postprandial serum insulin levels were significantly lower in thalassemics than in the controls. The mean serum ferritin level was higher in cases with diabetic glucose levels [2597.5 ng/mL] than those with normal glucose levels [1564 ng/mL]. Two patients showed higher fasting insulin levels [9.5-14 uU/mL] than the controls [6.9-8.3 uU/mL], despite the elevated blood glucose levels indicating an insulin resistance

Splenectomy and extraperitoneal splenic slice grafting in the treatment of thalassemia

The risk of total splenectomy in children with thalassemia is septicemia and overwhelming infection. Splenectomy with splenic slice grafting is an alternative in patients with thalassemia. 16 transfusion-dependent, high risk thalassemic patients [10 boys and 6 girls] underwent splenectomy and splenic slice grafting by the same surgeon from March 1998 to September 2001 at Health Insurance Hospital for children [Abu-Elrish Pupil Hospital], and El Hussein University Hospital. The patients age ranged from 4 to 8 years. The need for splenectomy in these cases was determined by the increasing need for blood transfusions and hypersplenism. Follow-up was from 1 to 4 years. Pre-and postoperative blood transfusions, length of operation, postoperative complications, fate of the grafts and their immune status before and after operation were evaluated. The procedure had good advantages of splenectomy and immunoconservation. Functioning splenic slice grafting which is detected by immunological assay and normal radionuclide splenic scan. Postoperatively there were no systemic infections or overwhelming post splenectomy sepsis. There was no incidence of death or rejection of the grafts during the follow-up period in our series. Splenectomy with splenic slice grafting greatly reduces and in some cases eliminates, the need for blood transfusions

Toxoplasmosis in children with neoplastic disease

Indirect fluorescent antibody test [I.F.A.T] IgG and IgM for Toxoplasmosis was performed in 94 children with neoplastic diseases: 54 patients with Acute Lymphoblastic Leukemia [18 at diagnosis and 18 during treatment, 18 at relapse] and 40 patients with Hodgkin's disease [16 at diagnosis, 16 during treatment, 8 at relapse]. The neoplastic groups were compared to 17 healthy control children of similar age and sex. In the control group 3/17 [17.6 percent], in Hodgkin's disease 16/40 [H.D] [40 percent] and A.L.L. 16/54 [29.6 percent] were Toxoplasma IgG positive. Reactivation or acquisition of Toxoplasmosis was shown by generation of specific IgM antibodies. All the control cases proved to be Toxoplasma IgM negative. The prevalence of IgM Toxoplasmosis in Hodgkin's disease was 12/40 [30 percent] while the prevalence in the group at diagnosis 4/16 [25 percent] was also statistically significant by comparison to the control group. Hodgkin's disease predispose patients to infection by Toxoplasmosis. In the relapse group of A.L.L 6/18 [33.3 percent] were Toxoplasma IgM positive' which was statistically significant by comparison to the control group and was also associated with a higher antibody titre level up to 1/256. Relapse may pave the way for infection by Toxoplasmosis in A.L.L., 60 percent of Toxoplasma IgM positive A.L.L. patients received blood transfusion, a higher percentage 66 percent was shown in the relapsing group of A.L.L. So we suggest the selection of only Toxoplasma antibody - negative subjects to serve as blood donors for the support of patients with A.L.L and H.D. In immunosuppressed patients with neoplasms there is a significant frequency of Toxoplasma infection, and to increase recognition of this complication, routine serologic testing of such patients should be instituted

Hepatitis B vaccination and immune response in children with malignant disease

Forty children with malignant disease were vaccinated by hepatitis B vaccine [recombinant]. Twenty children suffered of acute lymphoblastic leukemia [ALL] [Group I] and twenty patients with various forms of solid tumours [Group II]. The malignant patients were compared to twenty normal controls [Group III]. To evaluate the immune response we determined the antibody titres [Anti HBs] at Month 1, Month 2, Month 6, Month 7 from the first vaccination. At month 7 [1 month after the third vaccination dose] only 5 out of 20 in Group I seroconverted with a mean anti HBs of 16.6 mIU/ml, 10 out of 20 in Group II seroconverted with a mean anti HBs of 45.8 mIU/ml. In contrast in the control group, 19 out of 20 [95 percent], a full response was obtained with a mean antibody titre [Anti HBs of 460.4 mIU/ml]. We recommend that Children with acute lymphoblastic leukemia when necessary should be protected by passive immunisation against Hepatitis B as they have a markedly impaired immune response. While an early vaccination of patients suffering from solid tumours before the start of chemotherapy followed also by passive immunisation by injecting anti HBs immunoglobulin when indicated

Human immunodeficiency virus infection and hemophilic children's growth in Egypt

Forty multitransfused Egyptian Hemophiliacs [thirty Pediatrics and ten Adults were tested for anti HTLV [111] and HIV [1], the growth hormone, insulin, cortisol. thyroid hormones were also estimated. The growth parameters of the thirty Hemophilic boys were evaluated. Two pediatric hemophilic patients with HIV had significant growth failure and significantly lowered serum growth hormone level [GH] of 1.8 ng/ml and 1.4 ng/ml compared to the mean GH level of children with normal stature [3.4 +/- 0.4 ng/ml]. Other endocrine evaluation revealed that none of the pediatric hemophilic group had thyroid deficiency [T4: 9 +/- 1.2micro g/dl, T3: 140+56 ng/dl. TSH 3.l +/- 0.9 micro U/ ml]. None had insulin deficiency 5 +/- 2.4 micro U/ml versus control 4 +/- 1.6 micro U/ml. It appears that growth failure is not rare in boys with Hemophilia and HIV infection and this might be due to direct effect on the physiologic secretion of growth hormone

Adrenarche in Egyptian children with beta-thalassemia major

In this study 40 children with Beta-thalassaemia major were studied for the changing levels of dehydroepiandrosterone sulphate [DHEAS] with age starting from 5 to 13 years in order to detect the abrupt rise in DHEAS characteristic of the onset of adrenarche, i.e., the maturation of the adrenal gland. The children were studied for anthropometric measurements including weight, height, sitting height, biacromial and biiliac diameters. The hormones studied were DHEAS, cortisol, growth hormone and testosterone. The study showed that the maturation of the adrenal gland was incomplete and delayed to age 9 to 11 in children with Beta-thalassaemia major compared to 6 years as reported in healthy Egyptian children. The delay was less severe in females. No significant differences were observed with GH, testosterone and cortisol levels in prepubertal thalassaemic children. Splenectomized patients had significantly higher DHEAS levels, i.e. adrenal gland maturation was more developed than those with huge spleen. A significant negative correlation, was observed between DHEAS and GH [r -0.39] [p <0.05]. The weight, height and sitting height were > -2 S.D. in 45.16%, 65.71% and 78.26% respectively. Highly significant positive correlation were observed between DHEAS levels and weight [r 0.75 p < 0.01], height [r 0.66 p < 0.01], sitting height [r 0.062 p < 0.01], biacromial diameter [r 0.63 p < 0.01] and biiliac diameter [r 0.37 p < 0.05]. It is concluded that the severe growth retardation in thalassaemic children is definitely attributed partly if not wholly to the delayed and incomplete maturation of the adrenal gland in these children