Clinicovirologic analysis of hepatitis C infection in transfusion-dependent beta-thalassemia major children.

Regular blood transfusion puts beta-thalassemia major patients at a higher risk of developing hepatic iron overload and hepatitis C virus (HCV) infection. The association between several transfusion-related factors and an increased risk of developing HCV viremia has been reported. The effect of HCV infection on liver damage in transfusion-dependent thalassemia patients has been poorly described. A sample of 100 Egyptian transfusion-dependent beta-thalassemia major children were studied. Individual patients underwent full history taking, clinical examination and a panel of laboratory tests including HCV ribonucleic acid polymerase chain reaction (HCV-PCR) in blood samples. Liver biopsy was performed for 24 patients. HCV-PCR was positive in 64% of patients. A statistically significant correlation was found between HCV-PCR positivity (HCV viremia) and shorter inter-transfusion interval. There was a significant positive correlation between mean serum ferritin level and mean levels of alanine aminotransferase and aspartase aminotransferase. Histopathologic features of both chronic hepatitis and siderosis were present in 91.7% of biopsy specimens, and fibrosis was present in 41.67%. A higher risk of HCV viremia is noted with a shorter inter-transfusion interval. The reduced role of HCV infection in chronic liver injury in this group of patients may be surpassed by the associated effects of iron overload because of the chronic transfusion. However, the latter finding should be verified in larger studies.

The use of DNA markers for carrier detection and prenatal diagnosis of haemophilia A in Egyptian families.

Haemophilia A is the most common inherited X-linked recessive bleeding disorder. The aim was to investigate the usefulness of two DNA markers in linkage analysis, one intragenic BCL1 affecting restriction site in intron 18, and is detected as restriction fragment length polymorphism (RFLP), and one extragenic variable number of tandem repeat (VNTR) locus DXS52 (St14) to formulate an informative and accurate carrier detection and prenatal diagnosis. The study included 46 families with at least one child affected with haemophilia A, and 30 unrelated normal females as control group. Polymerase chain reaction (PCR) and restriction enzyme analysis were used to study the polymorphism in BCL1, and long-distance PCR for detection of VNTR (ST14) alleles. The incidence of BCL1 (+) allele was 74%, 72% and 60% in patients, mothers and control group, respectively. Expected heterozygosity for BCL1 was 40% in mothers of affected cases compared with 48% in the female control group. However, observed heterozygosity was found to be 48% in the mothers of affected cases, compared with 60% in the control group. Thus, 48% of the studied families are informative for this marker alone. Nine different alleles of VNTR (St14) were observed in mothers and six alleles in affected cases and six in the control group. The most prevalent alleles were 1300 bp (45.5% and 34%) and 700 bp (13.6% and 20%) in patients and their mothers, respectively. Observed heterozygosity in mothers was 41% compared with 43.3% in controls. The combined use of both BCL1 and St14 markers raised the informative rate to 63.6%. Carrier detection and prenatal diagnosis is possible in haemophilia A families using both DNA markers. We suggest screening haemophilic families first for BCL1 polymorphism followed by analysis of St14 locus.

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.

Suitability of soluble transferrin receptor for the clinical diagnosis of different types of anaemia in children.

We evaluated the ability of serum transferrin receptor (sTFR) to identify different types of anaemia in children. Thus 150 Egyptian children suffering from anaemia (iron deficiency anaemia, anaemia of chronic disease and beta-thalassaemia) were enrolled, together with 50 controls. There was a significant increase in the mean levels of sTFR in the groups with iron deficiency anaemia and thalassaemia, and a significant decrease in mean sTFR levels in the group with anaemia of chronic disease. Serum ferritin levels were significantly higher in all patient groups except the group with iron deficiency anaemia. There were also significant correlations between the sTFR and sTFR/log ferritin ratio (sTFR-F index) and different indices of iron status and of erythropoiesis. The sTFR-F index could be used as a diagnostic or screening tool for iron deficiency anaemia, anaemia of chronic disease and thalassaemia.

Suitability of soluble transferrin receptor for the clinical diagnosis of different types of anaemia in children

We evaluated the ability of serum transferrin receptor [sTFR] to identify different types of anaemia in children. Thus 150 Egyptian children suffering from anaemia [iron deficiency anaemia, anaemia of chronic disease and beta-thalassaemia] were enrolled, together with 50 controls. There was a significant increase in the mean levels of sTFR in the groups with iron deficiency anaemia and thalassaemia, and a significant decrease in mean sTFR levels in the group with anaemia of chronic disease. Serum ferritin levels were significantly higher in all patient groups except the group with iron deficiency anaemia. There were also significant correlations between the sTFR and sTFR/log ferritin ratio [sTFR-F index] and different indices of iron status and of erythropoiesis. The sTFR-F index could be used as a diagnostic or screening tool for iron deficiency anaemia, anaemia of chronic disease and thalassaemia

Viral etiology of obscure splenomegaly in Egyptian children.

Fifty seven Egyptian children aged 1.5 to 9.5 years with mild splenomegaly (less than 3 cm below the costal margin) were screened for antibodies against the three common viruses of the Herpes group: Cytomegalovirus (CMV), Epstein-Barr (EB) and Herpes type 1 virus. A group of 57 healthy children were studied similarly. All patients were subjected to a comprehensive laboratory and clinical work up to exclude any hematological, metabolic or malignant etiology for the splenomegaly. Splenic aspirates from five cases were examined histologically and by immunohistochemistry for the antigens of CMV. Only primary or reactivation of CMV might be considered a cause of splenomegaly, as there was a statistically significant increase in the prevalence of IgM antibodies to CMV in the patients compared to normal controls (63% of patients and 19.4% of controls had IgM antibodies, P less than 0.001; 68.3% of patients and 54% of controls had IgG antibodies, P is insignificant). An almost equal proportion of children with and without splenomegaly had antibodies to EB-Viral Capsid Antigen (EBVCA) both IgG and IgM. (28% of cases and 33% of controls had IgM antibodies; 26% of patients and 21% of controls had IgG antibodies). A role of Epstein-Barr viral infection could not be ruled out in these patients. There was a higher prevalence of antibodies to Herpes type 1 virus in asymptomatic controls than in children with splenomegaly. (10% of patients and 43% of controls had IgM antibodies, 10.6% of patients and 38% of controls had IgG antibodies).

Salivary female sex hormone levels and gingivitis in pregnancy.

Salivary estradiol 17 beta (E2-17 beta) and progesterone (P) were determined by using radioimmunoassay techniques in 30 pregnant females in the first, second and third trimesters as well as in 10 non-pregnant controls during the luteal phase of the menstrual cycle. Plaque index (P.I.), gingival index (G.I.) and retention index (R.I.) were measured in all cases. The data obtained showed that the levels of the two hormones in saliva were significantly increasing during the 3 trimesters of pregnancy. P.I. and R.I. did not change, however, G.I. was significantly higher in the second and third trimesters when compared with controls. A correlation between both E2--17 beta and P during pregnancy and gingival changes is suggested.